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*Medical Imaging - Principles and Applications*

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[77] Vogt BA, Finch DM, Olson CR. Functional heterogeneity in cingulate cortex: The anterior executive and posterior evaluative regions. Cerebral

[78] Vogt BA, Sikes RW. The medial pain system, cingulate cortex, and parallel processing of nociceptive information. Progress in Brain Research.

[79] Scrivani S, Wallin D, Moulton EA, et al. A fMRI evaluation of lamotrigine

for the treatment of trigeminal neuropathic pain: Pilot study. Pain Medicine. 2010;**11**(6):920-941

[80] De Ridder D, Vanneste S, Van Laere K, et al. Chasing map plasticity in neuropathic pain. World Neurosurgery.

[81] De Ridder D, Elgoyhen AB, Romo R, et al. Phantom percepts: Tinnitus and pain as persisting aversive memory networks. Proceedings of the National Academy of Sciences of the United States of America.

Cortex. 1992;**2**(6):435-443

2000;**122**:223-235

2013;**80**(6):901-905

2011;**108**(20):8075-8080

[82] Glasser MF, Coalson TS, Robinson EC, et al. A multi-modal parcellation of human cerebral cortex. Nature. 2016;**536**(7615):171-178

Henderson LA, et al. Brain circuitry underlying pain in response to imagined movement in people with spinal cord injury. Pain. 2010;**148**(3):438-445

[69] Diers M, Christmann C, Koeppe C, et al. Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. Pain.

[70] Cauda F, Sacco K, D'Agata F, et al. Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain. BMC Neuroscience. 2009;**10**:138

[71] Cifre I, Sitges C, Fraiman D, et al. Disrupted functional connectivity of the pain network in fibromyalgia.

mapping and functional connectivity of postherpetic neuralgia pain: A perfusion fMRI study. Pain. 2013;**154**(1):110-118

[73] Craddock RC, Holtzheimer PE, Hu XP, et al. Disease state prediction

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[74] Tracey I. Getting the pain you expect: Mechanisms of placebo, nocebo and reappraisal effects in humans. Nature Medicine. 2010;**16**(11):1277-1283

[75] Basbaum AI, Bautista DM, Scherrer G, et al. Cellular and molecular mechanisms of pain. Cell.

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[68] Gustin SM, Wrigley PJ,

**38**

Chapter 3

Evangelos Gazis

combination of PET with CT the PET-CT.

Abstract

PET-CT imaging

1. Introduction

PET and PET-CT imaging.

41

2. The ionizing radiation interaction with matter

The Ionizing Radiation Interaction

with Matter, the X-ray Computed

Tomography Imaging, the Nuclear

The mechanism of the ionizing radiation interaction with matter is described for heavy charged particles, electrons and photons. Those effects causing energy loss of the radiation with sequential effects of absorption or attenuation are presented. The features of some characteristic detector systems with the relative electronics and the data acquisition system (DAQ) are presented. Those detectors are related with the medical imaging sensor systems. The characteristics of the medical imaging process of the X-ray and nuclear imaging with SPECT, PET and the combination of PET-CT are presented. The computed X-ray tomography, called CT, and the nuclear medicine tomography are presented, implementing the most of the previous parts, as they are defined in PET and SPECT imaging plus the

Keywords: ionizing radiation, X-ray imaging, nuclear medicine, PET, SPECT,

The approach of this chapter is to cover physical principles of the interaction mechanisms of the ionizing radiation, the instrumental detector design and the relative electronics with the data acquisition setup, the image reconstruction techniques, and clinical applications of the imaging techniques most commonly used in clinical medicine as well as in academic research. It starts with the ionizing radiation interaction with matter for various particles and the properties then, the X-ray computed tomography, finishing with the nuclear medicine imaging with SPECT,

Unstable nuclei can emit a variety of electrically charged and neutral, particles as

well as electromagnetic radiation known as γ-rays (energetic photons).

Medicine SPECT, PET and

PET-CT Tomography Imaging

## Chapter 3

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging, the Nuclear Medicine SPECT, PET and PET-CT Tomography Imaging

Evangelos Gazis

## Abstract

The mechanism of the ionizing radiation interaction with matter is described for heavy charged particles, electrons and photons. Those effects causing energy loss of the radiation with sequential effects of absorption or attenuation are presented. The features of some characteristic detector systems with the relative electronics and the data acquisition system (DAQ) are presented. Those detectors are related with the medical imaging sensor systems. The characteristics of the medical imaging process of the X-ray and nuclear imaging with SPECT, PET and the combination of PET-CT are presented. The computed X-ray tomography, called CT, and the nuclear medicine tomography are presented, implementing the most of the previous parts, as they are defined in PET and SPECT imaging plus the combination of PET with CT the PET-CT.

Keywords: ionizing radiation, X-ray imaging, nuclear medicine, PET, SPECT, PET-CT imaging

## 1. Introduction

The approach of this chapter is to cover physical principles of the interaction mechanisms of the ionizing radiation, the instrumental detector design and the relative electronics with the data acquisition setup, the image reconstruction techniques, and clinical applications of the imaging techniques most commonly used in clinical medicine as well as in academic research. It starts with the ionizing radiation interaction with matter for various particles and the properties then, the X-ray computed tomography, finishing with the nuclear medicine imaging with SPECT, PET and PET-CT imaging.

## 2. The ionizing radiation interaction with matter

Unstable nuclei can emit a variety of electrically charged and neutral, particles as well as electromagnetic radiation known as γ-rays (energetic photons).

The best-known particle emission modes are the α-decay, in which a Helium nucleus is produced, and β-decay where an energetic electron e� (or a positron, e+) and an anti-neutrino (or a neutrino) are created. All these emissions are generically referred to as nuclear radiation. Their interaction with matter may occur via the electromagnetic, the strong or the week nuclear forces. An important issue in studying the passage of energetic nuclear radiation through matter is in understanding the transfer of energy produced. Energy transfer mechanisms depend on a number of factors, such as the type of radiation and its energy, as well as the physical properties of the irradiated material. Electrically charged particles, and γrays, of nuclear origin interact with highest probability with atomic excitation and ionization. In many of those processes, secondary electrons are produced which spread the energy deposition away from the primary interaction region. Measuring the effects of radiation on matter and finding out the relationship between them and the energy lost by the original radiation is the basis of all nuclear detection methods. When dealing with leaving matter, the biological impacts of such phenomena are the subject of much concern and study [1–4].

ð4Þ

ð5Þ

ð6Þ

Z = atomic number of the material, a = material-dependent constant.

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

the Figure 1.

number.

2.1.2 Bethe-Bloch relation

2.1.3 Range of alpha particles

alpha particles range:

Figure 1.

43

is given by the Bethe and Bloch formula [5–8].

DOI: http://dx.doi.org/10.5772/intechopen.84356

The trajectory of the charged alpha particle is unchanged after scattering, as in

Therefore, the mean energy loss for 'heavy' charged particles through the matter

Fundamental constants: re = classical radius of electron, NA = Avogadro's

absorber, δ = density correction, z = atomic number of the incident particle.

Absorber medium: I = mean ionization potential, approximately I = 16Z0.9 if Z > 1, Z = atomic number of absorber, A = atomic weight of absorber, ρ = density of

A heavy charged particle, such as an alpha particle, has a fairly definite range in a gas, liquid, or solid. The particle loses energy, primarily by the excitation and ionization of atoms in its path, occurs in a large number of small increments. The alpha particle has such a large momentum that its direction is not changed appreciably during the slowing processes. Eventually it loses all its kinetic energy and comes to rest. The distance traversed is called the range, and depends on the energy of the alpha particle, the atom density in the material traversed, and the atomic number and average ionization potential of the atoms comprising this material. Integrate over energy loss from the total energy T to the zero, it is obtained the

A plot of the specific ionization (number of ions formed per unit distance of beam path) versus distance from the alpha particle source for a beam of alpha particles is called a Bragg curve, should have the shape shown in Figure 2.

The alpha particle trajectory remains unchanged after ionizing the atom passing through.

#### 2.1 Interaction of alpha particles

The alpha particles (nuclei of Helium) have two protons and two neutrons bound together. Their mass is relatively large and carries a double positive charge. Alpha particles are commonly spontaneously emitted by the heavy radioactive nuclei occurring in the nature (Uranium, Thorium or Radium), as well as the transuranic elements (Neptunium, Plutonium or Americium). The high mass and charge of an alpha particle, relative to other forms of nuclear radiation, causes its greater ionization power and poorer ability to penetrate matter. A piece of paper can stop them. They travel only a few centimeters but deposit all their energies along their short paths.

#### 2.1.1 Stopping power

The alpha charged particles passing through matter lose kinetic energy by excitation of bound electrons and by ionization. The maximum transferable kinetic energy to an electron depends on the mass m0 and the momentum of the incident alpha particle. Given the momentum of the incident particle, p = γm0βc, where γ is the Lorentz factor (= E/m0c<sup>2</sup> ), βc = v the velocity, and m0 the rest mass; then the maximum transferable energy to electron with mass me is

$$E\_{km}^{\text{max}} = \frac{2m\_ec^2\mathcal{B}^2\mathcal{Y}^2}{1 + 2\mathcal{Y}m\_e/m\_0 + \left(m\_e/m\_0\right)^2} = \frac{2m\_ep^2}{m\_0^2 + m\_e^2 + 2m\_evE/c^2} \tag{1}$$

For low energies:

$$2\gamma m\_{\varepsilon}|m\_{0}\ll 1\tag{2}$$

and under the assumption that the incident alpha particles are heavier than electrons (m0 > me) Eq. (1) can be approximated by

$$E\_{\rm kin}^{\rm max} \approx 2m\_e c^2 \mathcal{B}^2 \mathcal{Y}^2 \tag{3}$$

The Energy loss for heavy charged particle per unit length [dE/dx], called stopping power, is given by

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

$$\frac{dE}{d\mathbf{x}} \approx \frac{Z^2}{\mathcal{J}^2} \ln\left(a\mathcal{J}^2 \mathcal{Y}^2\right) \tag{4}$$

Z = atomic number of the material, a = material-dependent constant.

The trajectory of the charged alpha particle is unchanged after scattering, as in the Figure 1.

#### 2.1.2 Bethe-Bloch relation

The best-known particle emission modes are the α-decay, in which a Helium nucleus is produced, and β-decay where an energetic electron e� (or a positron, e+) and an anti-neutrino (or a neutrino) are created. All these emissions are generically referred to as nuclear radiation. Their interaction with matter may occur via the electromagnetic, the strong or the week nuclear forces. An important issue in studying the passage of energetic nuclear radiation through matter is in understanding the transfer of energy produced. Energy transfer mechanisms depend on a number of factors, such as the type of radiation and its energy, as well as the physical properties of the irradiated material. Electrically charged particles, and γrays, of nuclear origin interact with highest probability with atomic excitation and ionization. In many of those processes, secondary electrons are produced which spread the energy deposition away from the primary interaction region. Measuring the effects of radiation on matter and finding out the relationship between them and the energy lost by the original radiation is the basis of all nuclear detection methods. When dealing with leaving matter, the biological impacts of such phe-

The alpha particles (nuclei of Helium) have two protons and two neutrons bound together. Their mass is relatively large and carries a double positive charge. Alpha particles are commonly spontaneously emitted by the heavy radioactive nuclei occurring in the nature (Uranium, Thorium or Radium), as well as the transuranic elements (Neptunium, Plutonium or Americium). The high mass and charge of an alpha particle, relative to other forms of nuclear radiation, causes its greater ionization power and poorer ability to penetrate matter. A piece of paper can stop them. They travel only a few centimeters but deposit all their energies

The alpha charged particles passing through matter lose kinetic energy by excitation of bound electrons and by ionization. The maximum transferable kinetic energy to an electron depends on the mass m0 and the momentum of the incident alpha particle. Given the momentum of the incident particle, p = γm0βc, where γ is

and under the assumption that the incident alpha particles are heavier than

The Energy loss for heavy charged particle per unit length [dE/dx], called

), βc = v the velocity, and m0 the rest mass; then the

ð1Þ

ð2Þ

ð3Þ

nomena are the subject of much concern and study [1–4].

maximum transferable energy to electron with mass me is

electrons (m0 > me) Eq. (1) can be approximated by

2.1 Interaction of alpha particles

Medical Imaging - Principles and Applications

along their short paths.

the Lorentz factor (= E/m0c<sup>2</sup>

For low energies:

stopping power, is given by

42

2.1.1 Stopping power

Therefore, the mean energy loss for 'heavy' charged particles through the matter is given by the Bethe and Bloch formula [5–8].

$$-\left\langle \frac{dE}{d\mathbf{x}} \right\rangle = 2\,\pi N\_A r\_e^2 \, m\_e c^2 \, \rho \frac{Z}{A} \frac{z^2}{\mathcal{J}^2} \left[ \ln \left( \frac{2m\_e c^2 \, \mathcal{J}^2 \mathcal{J}^2}{I^2} \right) - 2\,\mathcal{J}^2 - \delta(\beta \gamma) \right] \tag{5}$$

Fundamental constants: re = classical radius of electron, NA = Avogadro's number.

Absorber medium: I = mean ionization potential, approximately I = 16Z0.9 if Z > 1, Z = atomic number of absorber, A = atomic weight of absorber, ρ = density of absorber, δ = density correction, z = atomic number of the incident particle.

#### 2.1.3 Range of alpha particles

A heavy charged particle, such as an alpha particle, has a fairly definite range in a gas, liquid, or solid. The particle loses energy, primarily by the excitation and ionization of atoms in its path, occurs in a large number of small increments. The alpha particle has such a large momentum that its direction is not changed appreciably during the slowing processes. Eventually it loses all its kinetic energy and comes to rest. The distance traversed is called the range, and depends on the energy of the alpha particle, the atom density in the material traversed, and the atomic number and average ionization potential of the atoms comprising this material. Integrate over energy loss from the total energy T to the zero, it is obtained the alpha particles range:

$$R\left(T\right) = \int\_0^T \left[ -\frac{dE}{d\chi} \right]^{-1} dE\tag{6}$$

A plot of the specific ionization (number of ions formed per unit distance of beam path) versus distance from the alpha particle source for a beam of alpha particles is called a Bragg curve, should have the shape shown in Figure 2.

Dominating process for Ee > 10–30 MeV is not anymore ionization but the effect of Bremsstrahlung, where an electron accelerated in the Coulomb field of nucleus

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

The physical property of the radiation length for a material is that after passage

It is also defined a critical energy Ec, for which the energy loss due to ionization

In Figure 3, the electron energy loss is presented in Copper. The critical energy

The range of low-energy electrons (0.5 MeV ≤ Ekin ≤5 MeV) in Aluminum is

The electron energy loss is shown under the ionization and the Bremsstrahlung effect for an energy range

usually the energy loss due to Bremsstrahlung is written:

].

of one X0, the electron has lost all but (1/e)th of its initial energy [9]

ð8Þ

ð9Þ

ð10Þ

produces photon emission

DOI: http://dx.doi.org/10.5772/intechopen.84356

X0 = radiation length in [g/cm2

in this case is about 25 MeV.

described [10] by

Figure 3.

45

2–200 MeV.

2.2.2 Range of electrons/positrons

is equivalent to energy loss due to Bremsstrahlung:

Figure 2.

The alpha particles range in air. The trajectory called Bragg curve has the characteristic peak as the majority of the particles energy is deposited at the last stage of the curve.

#### 2.2 Interaction of electrons and positrons

The interaction of electrons with the matter follows the same mechanism of the charged particles with the absorbed material; taking into account that the incident and target electron have same mass me, so the incident and scattering electrons are identical and undistinguishable particles. Electrons as incident particles, however, play a special role in the treatment of the energy loss as the total energy loss of electrons even at low energies (MeV range) is influenced by bremsstrahlung processes. In addition, the ionization loss requires different treatment because the energy-transfer probability must be interpreted in a different way. One electron after the collision receives the energy Ekin and the other electron the rest of the energy E � mec<sup>2</sup> � Ekin, where E is the total energy of the incident electron.

The positrons have similar ionization loss as those of the electrons, having these particles are of equal mass, but not identical charge. Under the assumption that the positrons are antiparticles of electrons, there is, however, an additional consideration: if positrons come to rest, they will annihilate with an electron normally into two photons, which are emitted in opposite directions. Both photons have energies of 511 keV in the center-of-mass system, corresponding to the rest mass of the annihilated positron and electron.

#### 2.2.1 Energy loss of electrons/positrons

The energy loss of electrons in the matter can be calculated with the Bethe-Bloch formula, which needs modification, is described by1

$$- \left\langle \frac{dE}{d\kappa} \right\rangle\_{\text{Ionization}} \approx \ln \left\{ E \right\} \tag{7}$$

<sup>1</sup> The exact ionization energy loss of electrons for z = 1, is given by the parameter δ\* takes different values of the δ for the heavy charged particles. The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

Dominating process for Ee > 10–30 MeV is not anymore ionization but the effect of Bremsstrahlung, where an electron accelerated in the Coulomb field of nucleus produces photon emission

$$- \left\langle \frac{dE}{d\mathbf{x}} \right\rangle\_{Rrem} \approx \frac{E}{m^2} \tag{8}$$

usually the energy loss due to Bremsstrahlung is written:

$$-\left\langle \frac{dE}{d\mathbf{x}} \right\rangle\_{\text{Brom}} \approx \frac{E}{X\_0}, \quad X\_0 = \frac{A}{4aN\_A Z^2 r\_v^2 \ln \frac{183}{Z^{1/3}}}\tag{9}$$

X0 = radiation length in [g/cm2 ].

The physical property of the radiation length for a material is that after passage of one X0, the electron has lost all but (1/e)th of its initial energy [9]

It is also defined a critical energy Ec, for which the energy loss due to ionization is equivalent to energy loss due to Bremsstrahlung:

$$\left. \frac{dE}{d\mathbf{x}} (E\_c) \right|\_{\text{Brew}} = \frac{dE}{d\mathbf{x}} (E\_c) \Big|\_{\text{Ion}} \tag{10}$$

In Figure 3, the electron energy loss is presented in Copper. The critical energy in this case is about 25 MeV.

#### 2.2.2 Range of electrons/positrons

2.2 Interaction of electrons and positrons

the particles energy is deposited at the last stage of the curve.

Medical Imaging - Principles and Applications

Figure 2.

44

annihilated positron and electron.

2.2.1 Energy loss of electrons/positrons

formula, which needs modification, is described by1

<sup>1</sup> The exact ionization energy loss of electrons for z = 1, is given by

the parameter δ\* takes different values of the δ for the heavy charged particles.

The interaction of electrons with the matter follows the same mechanism of the charged particles with the absorbed material; taking into account that the incident and target electron have same mass me, so the incident and scattering electrons are identical and undistinguishable particles. Electrons as incident particles, however, play a special role in the treatment of the energy loss as the total energy loss of electrons even at low energies (MeV range) is influenced by bremsstrahlung processes. In addition, the ionization loss requires different treatment because the energy-transfer probability must be interpreted in a different way. One electron after the collision receives the energy Ekin and the other electron the rest of the energy E � mec<sup>2</sup> � Ekin, where E is the total energy of the incident electron.

The alpha particles range in air. The trajectory called Bragg curve has the characteristic peak as the majority of

The positrons have similar ionization loss as those of the electrons, having these particles are of equal mass, but not identical charge. Under the assumption that the positrons are antiparticles of electrons, there is, however, an additional consideration: if positrons come to rest, they will annihilate with an electron normally into two photons, which are emitted in opposite directions. Both photons have energies of 511 keV in the center-of-mass system, corresponding to the rest mass of the

The energy loss of electrons in the matter can be calculated with the Bethe-Bloch

ð7Þ

The range of low-energy electrons (0.5 MeV ≤ Ekin ≤5 MeV) in Aluminum is described [10] by

#### Figure 3.

The electron energy loss is shown under the ionization and the Bremsstrahlung effect for an energy range 2–200 MeV.

$$R\_e = 0.526 \left( E\_{kin} / MeV - 0.094 \right) \text{g/}cm^2 \tag{11}$$

through. Interactions of photons are fundamentally different from ionization processes of charged particles because in every photon interaction, the photon is either completely absorbed (photoelectric effect, pair production) or scattered through a relatively large angle meaning the Compton effect. Since the absorption or scattering is a statistical process, it is impossible to define a range for γ rays. A photon

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

measured in cm, the mass attenuation coefficient μ must be divided by the density ρ of the material. The mass attenuation coefficient μ is related to the cross sections for

where σ<sup>i</sup> is the atomic cross section for the process i, A is the atomic weight and NA is the Avogadro number. The mass attenuation coefficient, according to Eq. (14)

Atomic electrons absorb the energy of a photon completely. This effect is not possible for free electrons due to momentum conservation. The absorption of a photon by an atomic electron requires a third collision partner, which in this case is the atomic nucleus. The cross section for absorption of a photon of energy E<sup>γ</sup> in the K shell is extremely large (≈80% of the total cross section), because of the proximity of the third collision partner, the atomic nucleus, which absorbs the recoil momentum. The total photoelectric cross section in the non-relativistic range away from the absorption edges is given in the non-relativistic Born

is the Thomson cross section for elastic scattering of photons on electrons. For higher energies (ε >> 1) the energy dependence of the cross section for the

In Eqs. (15) and (17) the Z dependence of the cross section is approximated by

. This indicates that the photon does not interact with an isolated atomic electron. Z-dependent corrections, however, cause σphoto to be a more complicated function of Z. In the energy range between 0.1 MeV ≤ Eγ ≤ 5 MeV the exponent of Z varies

, depends strongly on the photon energy.

ð13Þ

ð14Þ

ð15Þ

ð16Þ

ð17Þ

. If the length is

beam is attenuated exponentially in matter according to.

DOI: http://dx.doi.org/10.5772/intechopen.84356

the various interaction processes of photons according to

where, ε = Eγ/mec<sup>2</sup> is the reduced photon energy and

photoelectric effect is much less pronounced,

given per g/cm<sup>2</sup>

2.4.1 Photoelectric effect

approximation by [12]

Z5

47

The length x in Eq. (13) is an area density with the unit g/cm<sup>2</sup>

In Figure 5 the electron range is plotted for various energies of electrons penetrating through a certain Aluminum absorber thickness [10, 11]. This figure shows the difficulty in the definition of a range of a particle due to the pronounced range straggling, in this case mainly due to the fact that electrons will experience multiple scattering and bremsstrahlung in the absorber. The extrapolation of the linear part of the curves shown in Figure 4 to the intersection with the abscissa defines the practical range [11].

#### 2.3 Linear energy transfer

The term "linear energy transfer (LET)" is used to indicate the average amount of energy that is lost per unit path-length as a charged particle travels through a given material and deposited in it. The LET for electrons is traditionally expressed in units of MeV/cm. In case, the value is divided by the mass density, then in units of MeV-cm2 /g. The average amount of energy deposited in a thin sample, per electron, can be estimated by multiplying the LET by the sample thickness. Similarly, the total energy deposited per gram of a specimen, following an exposure of N electrons/area, is

$$E = \frac{LET \cdot N}{\rho} \tag{12}$$

where, ρ is the mass density of the specimen material.

The energy deposited per gram is referred to as the radiation dose. Radiation doses are usually expressed in rads in the older literature, where 1 rad is equal to 100 erg/g. Alternatively the dose is expressed in the Standard International (SI) units of gray (Gy), where 1Gy = 1 J/kg, and thus 1 rad = 0.01 Gy. Since the dose is proportional to the electron exposure, it is commonly used to refer to the exposure as being the "dose." While this terminology is not strictly correct, the intended meaning becomes understandable in context.

#### 2.4 Interaction of photons: attenuation

Photons are detected indirectly via interactions in the material passed through. Subsequent ionization in the matter provides charged particles, which are spread

Figure 4. Absorption of electrons of various energies in aluminum foils [10, 11].

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

through. Interactions of photons are fundamentally different from ionization processes of charged particles because in every photon interaction, the photon is either completely absorbed (photoelectric effect, pair production) or scattered through a relatively large angle meaning the Compton effect. Since the absorption or scattering is a statistical process, it is impossible to define a range for γ rays. A photon beam is attenuated exponentially in matter according to.

$$I = I\_0 e^{-\mu \mathbf{x}} \tag{13}$$

The length x in Eq. (13) is an area density with the unit g/cm<sup>2</sup> . If the length is measured in cm, the mass attenuation coefficient μ must be divided by the density ρ of the material. The mass attenuation coefficient μ is related to the cross sections for the various interaction processes of photons according to

$$
\mu = \frac{N\_A}{A} \sum\_i \sigma\_i \tag{14}
$$

where σ<sup>i</sup> is the atomic cross section for the process i, A is the atomic weight and NA is the Avogadro number. The mass attenuation coefficient, according to Eq. (14) given per g/cm<sup>2</sup> , depends strongly on the photon energy.

#### 2.4.1 Photoelectric effect

ð11Þ

ð12Þ

In Figure 5 the electron range is plotted for various energies of electrons penetrating through a certain Aluminum absorber thickness [10, 11]. This figure shows the difficulty in the definition of a range of a particle due to the pronounced range straggling, in this case mainly due to the fact that electrons will experience multiple scattering and bremsstrahlung in the absorber. The extrapolation of the linear part of the curves shown in Figure 4 to the intersection with the abscissa defines the

The term "linear energy transfer (LET)" is used to indicate the average amount of energy that is lost per unit path-length as a charged particle travels through a given material and deposited in it. The LET for electrons is traditionally expressed in units of MeV/cm. In case, the value is divided by the mass density, then in units of

/g. The average amount of energy deposited in a thin sample, per electron,

can be estimated by multiplying the LET by the sample thickness. Similarly, the total energy deposited per gram of a specimen, following an exposure of N electrons/area, is

The energy deposited per gram is referred to as the radiation dose. Radiation doses are usually expressed in rads in the older literature, where 1 rad is equal to 100 erg/g. Alternatively the dose is expressed in the Standard International (SI) units of gray (Gy), where 1Gy = 1 J/kg, and thus 1 rad = 0.01 Gy. Since the dose is proportional to the electron exposure, it is commonly used to refer to the exposure as being the "dose." While this terminology is not strictly correct, the intended

Photons are detected indirectly via interactions in the material passed through. Subsequent ionization in the matter provides charged particles, which are spread

where, ρ is the mass density of the specimen material.

meaning becomes understandable in context.

Absorption of electrons of various energies in aluminum foils [10, 11].

2.4 Interaction of photons: attenuation

practical range [11].

MeV-cm2

Figure 4.

46

2.3 Linear energy transfer

Medical Imaging - Principles and Applications

Atomic electrons absorb the energy of a photon completely. This effect is not possible for free electrons due to momentum conservation. The absorption of a photon by an atomic electron requires a third collision partner, which in this case is the atomic nucleus. The cross section for absorption of a photon of energy E<sup>γ</sup> in the K shell is extremely large (≈80% of the total cross section), because of the proximity of the third collision partner, the atomic nucleus, which absorbs the recoil momentum. The total photoelectric cross section in the non-relativistic range away from the absorption edges is given in the non-relativistic Born approximation by [12]

$$
\sigma\_{photo}^{\kappa} = \left(\frac{32}{\varepsilon^{\gamma}}\right)^{1/2} \alpha^{4} \cdot Z^{\prime} \cdot \sigma\_{\eta h}^{\prime} \left[cm^{2}/atom\right] \tag{15}
$$

where, ε = Eγ/mec<sup>2</sup> is the reduced photon energy and

$$
\sigma\_{Th}^{\epsilon} = \frac{8}{3} \pi r\_{\epsilon}^{2} = 6.65 \cdot 10^{-25} \, cm^{2} \tag{16}
$$

is the Thomson cross section for elastic scattering of photons on electrons.

For higher energies (ε >> 1) the energy dependence of the cross section for the photoelectric effect is much less pronounced,

$$
\sigma\_{p\_{\rm photo}}^{\rm K} = 4 \,\pi r\_{\rm e}^2 \alpha^4 \cdot Z^{\rm S} \cdot \frac{1}{\varepsilon} \tag{17}
$$

In Eqs. (15) and (17) the Z dependence of the cross section is approximated by Z5 . This indicates that the photon does not interact with an isolated atomic electron. Z-dependent corrections, however, cause σphoto to be a more complicated function of Z. In the energy range between 0.1 MeV ≤ Eγ ≤ 5 MeV the exponent of Z varies

between 4 and 5. As a consequence of the photoelectric effect in an inner shell (e.g., of the K shell) secondary effects may occur, as the free place, e.g., in the K shell, is filled by an electron from a higher shell, the energy difference between those two shells can be liberated in the form of X rays of characteristic energy.

#### 2.4.1.1 Compton scattering

The Compton effect is the scattering of photons off quasi-free atomic electrons. In the study of this interaction process, the binding energy of the atomic electrons is neglected. The total cross section for Compton scattering per electron is given by [12]

$$\sigma\_{\varepsilon}^{\prime} = 2\pi r\_{\varepsilon}^{2} \left\langle \left(\frac{1+\varepsilon}{\varepsilon}\right) \left[\frac{2\left(1+\varepsilon\right)}{1+2\varepsilon} - \frac{1}{\varepsilon}\ln\left(1+2\varepsilon\right)\right] + \frac{1}{2\varepsilon}\ln\left(1+2\varepsilon\right) - \frac{1+3\varepsilon}{\left(1+2\varepsilon\right)^{2}} \right\rangle \left[\varepsilon m^{2}/\text{eloctron}\right], \quad \varepsilon = \frac{E\_{r}}{m\_{\varepsilon}\varepsilon^{2}} \quad \text{(128)}$$

For Compton scattering off atoms the cross section is increased by the factor Z, because there are exactly Z electrons as possible scattering centers in an atom; consequently

In Compton-scattering process only a fraction of the photon energy is transferred to the electron. Therefore, one defines an energy scattering cross section

$$
\sigma\_{cs} = \frac{E\_\gamma'}{E\_\gamma} \cdot \sigma\_\circ' \tag{19}
$$

The pair-production cross section is given by [22]

DOI: http://dx.doi.org/10.5772/intechopen.84356

energy-independent value which is given approximately by

total mass absorption coefficient (μ<sup>a</sup> = μph + μ<sup>p</sup> + μca).

scattering, etc.) are governed by extremely low cross sections.

absorber [11, 12].

num and Lead [13, 14].

particle astrophysics.

Figure 5.

49

photon energy and the target charge number Z [11, 12].

2.5 Radiation detection

2.4.3 Total photon absorption cross section and mass attenuation coefficient

For large photon energies, the pair-production cross section approaches an

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

Ranges, in which the individual photon interaction processes dominate, are plotted in Figure 5 as a function of the photon energy and the atomic number of the

The total mass attenuation coefficient, which is related to the cross sections according to Eq. (14), is shown in Figures 6–9 for the absorbers water, air, Alumi-

The μph is the absorption coefficient for the photoelectric effect, μcs the Compton scattering, μca the Compton absorption and μ<sup>p</sup> the pair production. So μ<sup>a</sup> is the

Therefore, these processes are of little importance for the detection of photons. However, these processes are of large interest in elementary particle physics and

The detection of ionizing radiation in various energy ranges from keV to MeV is presented. The physical processes of radiation/matter interaction have been introduced in the previous text. All the steps of detection are covered, as well as detectors, instrumentations and measurements methods commonly used in the

Ranges in which the photoelectric effect, Compton effect and pair production dominate as a function of the

Further interactions of photons (photonuclear interactions, photon–photon

ð22Þ

ð23Þ

where, the energy E'<sup>γ</sup> = Eγ–Ekin and the Ekin is transferred to the target electron.

The Compton scattering is a special effect for photon interactions, because only part of the photon energy is transferred to the target electron, one has to distinguish between the mass attenuation coefficient and the mass absorption coefficient. The mass attenuation coefficient μcs is related to the Compton-energy scattering cross section σcs, as in Eq. (19), according to Eq. (14). Correspondingly, the mass absorption coefficient μca is calculated from the energy absorption cross-section σca, Eq. (14). For various absorbers the Compton-scattering cross sections, or absorption coefficients, have been multiplied by the atomic number of the absorber, since the Compton scattering cross section, Eq. (18), given by the Klein–Nishina formula is valid per electron, but in this case, the atomic cross sections are required.

#### 2.4.2 Pair production

The production of electron–positron pairs in the Coulomb field of a nucleus is only possible if the photon energy exceeds a certain threshold. This threshold energy is given by the rest masses of two electrons plus the recoil energy, which is transferred to the nucleus. From energy and momentum conservation, this threshold energy can be calculated to be

$$E\_{\gamma} \ge 2 \, m\_{\text{e}} c^2 + 2 \frac{m\_{\text{e}}^2}{m\_{\text{mclons}}} c^2 \tag{20}$$

but usually the effective threshold can be approximately

$$E\_{\gamma} \ge 2m\_{\varrho}c^2 \tag{21}$$

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

The pair-production cross section is given by [22]

between 4 and 5. As a consequence of the photoelectric effect in an inner shell (e.g., of the K shell) secondary effects may occur, as the free place, e.g., in the K shell, is filled by an electron from a higher shell, the energy difference between those two

The Compton effect is the scattering of photons off quasi-free atomic electrons. In the study of this interaction process, the binding energy of the atomic electrons is neglected. The total cross section for Compton scattering per electron is given

For Compton scattering off atoms the cross section is increased by the factor Z,

In Compton-scattering process only a fraction of the photon energy is transferred to the electron. Therefore, one defines an energy scattering cross section

where, the energy E'<sup>γ</sup> = Eγ–Ekin and the Ekin is transferred to the target electron. The Compton scattering is a special effect for photon interactions, because only part of the photon energy is transferred to the target electron, one has to distinguish between the mass attenuation coefficient and the mass absorption coefficient. The mass attenuation coefficient μcs is related to the Compton-energy scattering cross section σcs, as in Eq. (19), according to Eq. (14). Correspondingly, the mass absorption coefficient μca is calculated from the energy absorption cross-section σca, Eq. (14). For various absorbers the Compton-scattering cross sections, or absorption coefficients, have been multiplied by the atomic number of the absorber, since the Compton scattering cross section, Eq. (18), given by the Klein–Nishina formula

is valid per electron, but in this case, the atomic cross sections are required.

but usually the effective threshold can be approximately

The production of electron–positron pairs in the Coulomb field of a nucleus is only possible if the photon energy exceeds a certain threshold. This threshold energy is given by the rest masses of two electrons plus the recoil energy, which is transferred to the nucleus. From energy and momentum conservation, this thresh-

because there are exactly Z electrons as possible scattering centers in an atom;

ð18Þ

ð19Þ

ð20Þ

ð21Þ

shells can be liberated in the form of X rays of characteristic energy.

2.4.1.1 Compton scattering

Medical Imaging - Principles and Applications

by [12]

consequently

2.4.2 Pair production

48

old energy can be calculated to be

$$
\sigma\_{polr} = 4 \,\mathrm{or}\_{\,\,e}^2 \cdot Z^2 \left(\frac{7}{9} \ln 2 \,\mathrm{c} - \frac{109}{54}\right) \left[\,\mathrm{cm}^2/atom\right] \tag{22}
$$

For large photon energies, the pair-production cross section approaches an energy-independent value which is given approximately by

$$
\sigma\_{\mu vr} \approx \frac{7}{9} 4 \,\mathrm{\alpha} r\_v^2 \cdot Z^2 \ln \frac{183}{Z^{1/3}} \approx \frac{7}{9} \cdot \frac{A}{N\_A} \cdot \frac{1}{X\_0} \tag{23}
$$

#### 2.4.3 Total photon absorption cross section and mass attenuation coefficient

Ranges, in which the individual photon interaction processes dominate, are plotted in Figure 5 as a function of the photon energy and the atomic number of the absorber [11, 12].

The total mass attenuation coefficient, which is related to the cross sections according to Eq. (14), is shown in Figures 6–9 for the absorbers water, air, Aluminum and Lead [13, 14].

The μph is the absorption coefficient for the photoelectric effect, μcs the Compton scattering, μca the Compton absorption and μ<sup>p</sup> the pair production. So μ<sup>a</sup> is the total mass absorption coefficient (μ<sup>a</sup> = μph + μ<sup>p</sup> + μca).

Further interactions of photons (photonuclear interactions, photon–photon scattering, etc.) are governed by extremely low cross sections.

Therefore, these processes are of little importance for the detection of photons. However, these processes are of large interest in elementary particle physics and particle astrophysics.

#### 2.5 Radiation detection

The detection of ionizing radiation in various energy ranges from keV to MeV is presented. The physical processes of radiation/matter interaction have been introduced in the previous text. All the steps of detection are covered, as well as detectors, instrumentations and measurements methods commonly used in the

Figure 5.

Ranges in which the photoelectric effect, Compton effect and pair production dominate as a function of the photon energy and the target charge number Z [11, 12].

Figure 6. Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in water.

Figure 7. Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in Air.

nuclear field. There are many radiation detectors being developed so far. A selection of the most characteristic detectors will be presented, having played crucial role to the nuclear imaging.

excitation of gas molecules along the particle track. An electronic output signal is derived originating from the ion pairs formed within the gas filling the detector. The charged particle transfers an amount of energy equal to the ionization energy of the gas molecule to permit the ionization process to occur. In most gases of interest for radiation detectors, the ionization energy for the least tightly bound electron shells is roughly 10 to 25 eV. The neutral atoms or molecules of the gas are in

Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in Lead.

Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

DOI: http://dx.doi.org/10.5772/intechopen.84356

Figure 8.

Aluminum.

Figure 9.

51

#### 2.5.1 Ionizing chambers

This radiation detector is based on the effects produced by a charged particle passing through a gas. The primary modes of interaction involve ionization and

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

Figure 8.

Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in Aluminum.

Figure 9. Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in Lead.

excitation of gas molecules along the particle track. An electronic output signal is derived originating from the ion pairs formed within the gas filling the detector. The charged particle transfers an amount of energy equal to the ionization energy of the gas molecule to permit the ionization process to occur. In most gases of interest for radiation detectors, the ionization energy for the least tightly bound electron shells is roughly 10 to 25 eV. The neutral atoms or molecules of the gas are in

nuclear field. There are many radiation detectors being developed so far. A selection of the most characteristic detectors will be presented, having played crucial role to

Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in Air.

Energy dependence of the mass attenuation coefficient μ and mass absorption coefficient μ<sup>a</sup> for photons in water.

This radiation detector is based on the effects produced by a charged particle passing through a gas. The primary modes of interaction involve ionization and

the nuclear imaging.

Figure 7.

50

Figure 6.

Medical Imaging - Principles and Applications

2.5.1 Ionizing chambers

constant thermal motion; characterized by a mean free path for typical gases under standard conditions of about 10<sup>6</sup> –108 m. A typical value of the average energy lost by the incident particle per ion pair formed is 25–35 eV/ion pair. Therefore, an incident 1 MeV particle, if it is fully stopped within the gas, will create about 30,000 ion pairs. A point-like collection of free electrons spread around the original point into a Gaussian spatial distribution; where the width increases by the time. An external electric field is applied to the ionization chamber; where ions or electrons created in the gas by the incident particle, electrostatic forces tend to move the charges away from their point of origin. The net motion consists of a superposition of a random thermal velocity together with a net drift velocity in a given direction. The drift velocity for positive ions is in the direction of the conventional electric field, whereas free electrons and negative ions drift in the opposite direction. Finally the total charge collection constitutes an electric current, the called ionization current. The magnitude of the ionization current is too small to be measured usually by a galvanometer. An active amplification of the current is implemented by sensing the voltage drop across a series resistance placed in the measuring circuit. The voltage developed across the resistor (i.e., a value of 10<sup>9</sup> –10<sup>12</sup> Ohms) can be amplified used for the measured signal. An alternative approach is to convert the signal from dc to ac at an early stage, which then allows a more stable amplification of the ac signal in subsequent stages. This conversion is accomplished in the dynamiccapacitor or vibrating reed electrometer by collecting the ion current across an RC circuit with long time constant. A charge Q is stored on the capacitance, which is given by Q = CV. If a charge ΔQ is created by the radiation, then the total charge stored on the capacitance will be reduced by ΔQ. The voltage will therefore drop from its original value of Vo by an amount ΔV given by.

$$
\Delta V = \frac{\Delta Q}{C} \tag{24}
$$

very fast timing procedures. It has become common to specify the performance of ultrafast organic scintillators by their FWHM time rather than the decay time alone. It is noted that both rise and decay time are of the order of ns. The alkali halide scintillators as the Sodium Iodide with trace of Thallium NaI(Tl) and the Cesium

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

implemented for gamma spectroscopy and medical imaging applications. An alternative scintillation material, Bi4Ge3OI2 (BGO) is available as crystals of reasonable

number (83) of the Bismuth element. These properties result in the largest probability per unit volume for the photoelectric absorption of gamma rays. Its physical properties make it easy to handle and use. The light yield from BGO is relatively

The use of a solid detection medium in many radiation detection applications is of great advantage, as for the measurement of high-energy electrons or gamma rays. The detector dimensions can be kept much smaller than the equivalent gas-filled detector because the solid densities are some 1000 times greater than that for a gas. The use of semiconductor materials as radiation detectors can result in a much larger number of carriers for a given incident radiation event than is possible with any other common detector type, described previously. Consequently, the best energy resolution from radiation spectrometers is achieved using semiconductor detectors. The fundamental information carriers are electron-hole pairs created along the path taken by the charged particle of the primary radiation or secondary particle through the detector. The electron-hole pair is somewhat analogous to the ion pair created in gas-filled detectors. Their motion in an applied electric field generates the basic electrical signal from the detector. Under low values of the electric field intensity, the drift velocity v is proportional to the applied field. Then a

where, E is the electric field magnitude. We have seen, that the mobility of the free electron in the gas is much larger than of the positive ion, but in semiconductor materials the mobility of the electron and hole are roughly of the same order, saturated by the increased electric field to value of the order of 10<sup>7</sup> cm/s. When a charged particle passes through a semiconductor the overall significant effect is the production of many equal numbers electron–hole pairs along the track of the particle. The process produces high-energy electrons or delta rays that subsequently lose their energy in producing more electron–hole pairs. This quantity, is called the ionization energy, is experimentally observed to be largely independent of both the energy and type of the incident radiation, provided the charge particle is fully

The Si surface barrier detectors have widespread application for the detection of

alpha particles and other short-range radiations but are not easily adaptable for applications that involve more penetrating radiations. Their major limitation is the maximum depletion depth or active volume that can be created. Using Silicon or Germanium of normal semiconductor purity, depletion depths beyond 2 or 3 mm are difficult to achieve despite applying bias voltages that are near the breakdown level. A low impurity concentration corresponds to levels that are less than 1 part in 1012, a virtually unprecedented degree of material purity. Techniques have been

) and the large atomic

ð25Þ

Iodide with trace of Thallium or Sodium CsI(Tl)/CsI(Na) are so broadly

size. A major advantage is the high density (7.13 g/cm<sup>3</sup>

DOI: http://dx.doi.org/10.5772/intechopen.84356

2.5.3 Si/Ge solid state detectors

low, being variously reported at 10–20% of that of NaI(Tl).

mobility μ for both electrons and holes can be defined by.

stopped within the active volume of the detector.

53

A measurement of ΔV provides the total ionization charge or the integrated ionization current over the period of the measurement.

#### 2.5.2 Scintillator detectors

Scintillation detectors offer one possibility of providing a solid detection medium, and their application to the detection and measurement of various radiations. The detection of ionizing radiation by the scintillation light produced in certain materials is a very well established technique and remains one of the most useful methods available for the detection and spectroscopy of a wide variety of radiations. The kinetic energy of charged particles is converted into detectable light, by subsequent photosensitive detector, with high scintillation process efficiency. The conversion is taken care to be linear and the light yield to be proportional to the deposited energy over the most possible wide range. The scintillating material should be transparent to the wavelength of its own emission for total light collection. The decay time of the induced luminescence is short and then fast signal pulses can be generated. The process of fluorescence is the prompt emission of visible radiation from a substance following its excitation by incident radiation. It is conventional to distinguish several other processes that can also lead to the emission of visible light. The scintillation efficiency of any scintillator is defined as the fraction of all incident particle energy, which is converted into visible light. The rise and fall of the light output can be characterized by the full width at half maximum (FWHM) of the resulting light versus time profile, which can be measured using

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

very fast timing procedures. It has become common to specify the performance of ultrafast organic scintillators by their FWHM time rather than the decay time alone. It is noted that both rise and decay time are of the order of ns. The alkali halide scintillators as the Sodium Iodide with trace of Thallium NaI(Tl) and the Cesium Iodide with trace of Thallium or Sodium CsI(Tl)/CsI(Na) are so broadly implemented for gamma spectroscopy and medical imaging applications. An alternative scintillation material, Bi4Ge3OI2 (BGO) is available as crystals of reasonable size. A major advantage is the high density (7.13 g/cm<sup>3</sup> ) and the large atomic number (83) of the Bismuth element. These properties result in the largest probability per unit volume for the photoelectric absorption of gamma rays. Its physical properties make it easy to handle and use. The light yield from BGO is relatively low, being variously reported at 10–20% of that of NaI(Tl).

#### 2.5.3 Si/Ge solid state detectors

constant thermal motion; characterized by a mean free path for typical gases under

by the incident particle per ion pair formed is 25–35 eV/ion pair. Therefore, an incident 1 MeV particle, if it is fully stopped within the gas, will create about 30,000 ion pairs. A point-like collection of free electrons spread around the original point into a Gaussian spatial distribution; where the width increases by the time. An external electric field is applied to the ionization chamber; where ions or electrons created in the gas by the incident particle, electrostatic forces tend to move the charges away from their point of origin. The net motion consists of a superposition of a random thermal velocity together with a net drift velocity in a given direction. The drift velocity for positive ions is in the direction of the conventional electric field, whereas free electrons and negative ions drift in the opposite direction. Finally the total charge collection constitutes an electric current, the called ionization current. The magnitude of the ionization current is too small to be measured usually by a galvanometer. An active amplification of the current is implemented by sensing the voltage drop across a series resistance placed in the measuring circuit. The

fied used for the measured signal. An alternative approach is to convert the signal from dc to ac at an early stage, which then allows a more stable amplification of the ac signal in subsequent stages. This conversion is accomplished in the dynamiccapacitor or vibrating reed electrometer by collecting the ion current across an RC circuit with long time constant. A charge Q is stored on the capacitance, which is given by Q = CV. If a charge ΔQ is created by the radiation, then the total charge stored on the capacitance will be reduced by ΔQ. The voltage will therefore drop

A measurement of ΔV provides the total ionization charge or the integrated

Scintillation detectors offer one possibility of providing a solid detection medium, and their application to the detection and measurement of various radiations. The detection of ionizing radiation by the scintillation light produced in certain materials is a very well established technique and remains one of the most useful methods available for the detection and spectroscopy of a wide variety of radiations. The kinetic energy of charged particles is converted into detectable light, by subsequent photosensitive detector, with high scintillation process efficiency. The conversion is taken care to be linear and the light yield to be proportional to the deposited energy over the most possible wide range. The scintillating material should be transparent to the wavelength of its own emission for total light collection. The decay time of the induced luminescence is short and then fast signal pulses can be generated. The process of fluorescence is the prompt emission of visible radiation from a substance following its excitation by incident radiation. It is conventional to distinguish several other processes that can also lead to the emission of visible light. The scintillation efficiency of any scintillator is defined as the fraction of all incident particle energy, which is converted into visible light. The rise and fall

of the light output can be characterized by the full width at half maximum (FWHM) of the resulting light versus time profile, which can be measured using

voltage developed across the resistor (i.e., a value of 10<sup>9</sup>

from its original value of Vo by an amount ΔV given by.

ionization current over the period of the measurement.

2.5.2 Scintillator detectors

52

–108 m. A typical value of the average energy lost

–10<sup>12</sup> Ohms) can be ampli-

ð24Þ

standard conditions of about 10<sup>6</sup>

Medical Imaging - Principles and Applications

The use of a solid detection medium in many radiation detection applications is of great advantage, as for the measurement of high-energy electrons or gamma rays. The detector dimensions can be kept much smaller than the equivalent gas-filled detector because the solid densities are some 1000 times greater than that for a gas. The use of semiconductor materials as radiation detectors can result in a much larger number of carriers for a given incident radiation event than is possible with any other common detector type, described previously. Consequently, the best energy resolution from radiation spectrometers is achieved using semiconductor detectors. The fundamental information carriers are electron-hole pairs created along the path taken by the charged particle of the primary radiation or secondary particle through the detector. The electron-hole pair is somewhat analogous to the ion pair created in gas-filled detectors. Their motion in an applied electric field generates the basic electrical signal from the detector. Under low values of the electric field intensity, the drift velocity v is proportional to the applied field. Then a mobility μ for both electrons and holes can be defined by.

$$\nu\_{\mathfrak{e}} = \mu\_{\mathfrak{e}} E \quad \nu\_{h} = \mu\_{h} E \tag{25}$$

where, E is the electric field magnitude. We have seen, that the mobility of the free electron in the gas is much larger than of the positive ion, but in semiconductor materials the mobility of the electron and hole are roughly of the same order, saturated by the increased electric field to value of the order of 10<sup>7</sup> cm/s. When a charged particle passes through a semiconductor the overall significant effect is the production of many equal numbers electron–hole pairs along the track of the particle. The process produces high-energy electrons or delta rays that subsequently lose their energy in producing more electron–hole pairs. This quantity, is called the ionization energy, is experimentally observed to be largely independent of both the energy and type of the incident radiation, provided the charge particle is fully stopped within the active volume of the detector.

The Si surface barrier detectors have widespread application for the detection of alpha particles and other short-range radiations but are not easily adaptable for applications that involve more penetrating radiations. Their major limitation is the maximum depletion depth or active volume that can be created. Using Silicon or Germanium of normal semiconductor purity, depletion depths beyond 2 or 3 mm are difficult to achieve despite applying bias voltages that are near the breakdown level. A low impurity concentration corresponds to levels that are less than 1 part in 1012, a virtually unprecedented degree of material purity. Techniques have been

developed to achieve this goal in Germanium, but not in Silicon. The process of Lithium ion drifting has been applied in both Silicon, Si(Li), and Germanium, Ge (Li), crystals to compensate the material after the crystal has been grown. Detectors that are manufactured from this ultrapure Germanium are usually called high purity Germanium (HPGe) detectors, and they have become available with depletion depths of several centimeters. The room-temperature operation of Germanium detectors is impossible because of the large thermally induced leakage current, due to the small band gap (1 eV). So, the Germanium detectors must be cooled to reduce the leakage current to the point that the associated noise does not spoil their excellent energy resolution. Normally, the operation temperature is at 77 K through the use of an insulated Dewar vessel, which a reservoir of liquid Nitrogen is kept in thermal contact with the detector. For Ge(Li) detectors, the low temperature must be maintained continuously to prevent a catastrophic redistribution of the drifted lithium that will rapidly take place at room temperature.

the information carried by the maximum amplitude of the pulse has been preserved. The pulses have been shaped in the sense that their total length has been reduced drastically but not affecting the maximum amplitude. The nuclear pulse shaping, it is conventional to make an important distinction between differentiator or CR networks and integrator or RC. Both operations can also be thought of as filtering in the frequency domain, for pulse shaping to improve signal-to-noise ratio by limiting the response of the instrumentation to those frequency ranges in which the signal has useful components. This type of pulse shaping is conventionally carried out in the linear amplifier element of a nuclear pulse signal chain and then to the digital pulse processing, for getting a digitized version of the input waveform for further analysis. A linear pulse is defined as a signal pulse that carries information through its amplitude, and sometimes by its shape as well. A sequence of linear pulses may therefore differ widely in size and shape characteristics. In addition, a logic pulse is a signal pulse of standard size and shape that carries information only by its presence or absence, or by the precise time of its appearance. Usually, all radiation detector signal chains start out with linear pulses, which after passing fixed amplitude discrimination, a digital conversion provides the logic pulses by the ADC (Analog to Digital Converter) elements. The information on the precise arrival time of a quantum of radiation in the detector is of particular interest. The accuracy of the timing information to be performed depends both on the properties of the specific detector, where the signal charge is collected rapidly and the type of electronics used to process the signal. The timing characteristics of a certain system depend greatly on the dynamic range, ratio of maximum to minimum pulse height, of the signal pulses. The time resolution is defined by the time measurement accuracy of the system. Similar spatial resolution of a nuclear chain is defined for acquiring the discrimination of two same radiation quanta passing in nearby places

DOI: http://dx.doi.org/10.5772/intechopen.84356

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

2.6.2 Multi-channel analysis and measurements: principle of measurements,

spectrometry, common detection instrumentations, applications in nuclear

A measurement of the differential pulse height spectrum from a radiation detector can yield important information on the nature of the incident radiation or the properties of the detector itself and is therefore one of the most important functions to be performed in nuclear measurements. By definition, the differential pulse height spectrum is a continuous curve that plots the value of dN/dH, the differential number of pulses observed within a differential increment of pulse

The multichannel analyzer (MCA) is comprised of basic electronics components chain setup. The major task of its operation is based on the principle of converting an analog signal (the pulse amplitude) to an equivalent digital number. Then, an extensive technology available for the storage and display of the digital information provides the recording pulse height spectra. As a result, the analog to-digital converter (ADC) is a key element in determining the performance characteristics of the

The nuclear instrumentation, mainly, based by the detector, the electronic system, the MCA and the data storage-analysis medium, can be properly adapted for several applications. Those applications are starting form the nuclear engineering instrumentation for nuclear reactors monitoring and safety, to various research instrumentations for accelerators or detector systems and so on. All these

of a detector.

analyzer.

55

engineering and R&D

height H, versus the value of the pulse height H.

### 2.5.4 Pixel detectors

The approach to obtain two-dimensional position information from a single sided silicon detector is to fabricate the top electrode as a checkerboard pattern of individual small elements that are electrically isolated from each other. If the electrode dimensions are smaller than 1 mm, the common terminology is pixel detector. Electrical connection must be made to each individual electrode and separate electronic readout channels provided for each. This approach has the advantage that the small size of each individual electrode results in a relatively small capacitance and leakage current, and thus the electronic noise is reduced considerably from that observed from microstrip detectors of equivalent dimensions. In the usual approach, a pixel detector chip is connected to a separate readout chip using flip chip solder bonding or Indium bump bonds. The readout chip is fabricated with exactly the same pitch as the detector pixels, so each bump provides an electrical connection between a single pixel and its corresponding readout electronics. Pixel detectors typically have active areas that are limited to the order of square centimeters. Larger detector areas can be achieved by assembling individual modules into arrays, although at the expense of increasing complexity in what is already a complex device.

### 2.6 Electronics and DAQ

Complicated electronic systems are adapted to get the information of the signal extraction by the radiation detectors. After an analog and digital treatment of the detector plus electronics waveform; a data acquisition system (DAQ) is accumulating the data for further analysis and study.

#### 2.6.1 Signal processing and analysis: types of electronics, signal collection and amplification, particle discrimination, spatial and time resolution

It is often desirable to change the shape of the pulse signal from radiation detectors, in some predetermined fashion. It is the most common application in processing a train of pulses produced by a preamplifier. In order to ensure that complete charge collection occurs, preamplifiers are normally adjusted to provide a decay time for the pulse, which is quite long, typically 50 μs. Depending of the rate of interaction in the detector these pulses will tend to overlap one another and give rise to a pulse train. The ideal shape is to eliminate the long tails of the pulses, but

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

the information carried by the maximum amplitude of the pulse has been preserved. The pulses have been shaped in the sense that their total length has been reduced drastically but not affecting the maximum amplitude. The nuclear pulse shaping, it is conventional to make an important distinction between differentiator or CR networks and integrator or RC. Both operations can also be thought of as filtering in the frequency domain, for pulse shaping to improve signal-to-noise ratio by limiting the response of the instrumentation to those frequency ranges in which the signal has useful components. This type of pulse shaping is conventionally carried out in the linear amplifier element of a nuclear pulse signal chain and then to the digital pulse processing, for getting a digitized version of the input waveform for further analysis. A linear pulse is defined as a signal pulse that carries information through its amplitude, and sometimes by its shape as well. A sequence of linear pulses may therefore differ widely in size and shape characteristics. In addition, a logic pulse is a signal pulse of standard size and shape that carries information only by its presence or absence, or by the precise time of its appearance. Usually, all radiation detector signal chains start out with linear pulses, which after passing fixed amplitude discrimination, a digital conversion provides the logic pulses by the ADC (Analog to Digital Converter) elements. The information on the precise arrival time of a quantum of radiation in the detector is of particular interest. The accuracy of the timing information to be performed depends both on the properties of the specific detector, where the signal charge is collected rapidly and the type of electronics used to process the signal. The timing characteristics of a certain system depend greatly on the dynamic range, ratio of maximum to minimum pulse height, of the signal pulses. The time resolution is defined by the time measurement accuracy of the system. Similar spatial resolution of a nuclear chain is defined for acquiring the discrimination of two same radiation quanta passing in nearby places of a detector.

### 2.6.2 Multi-channel analysis and measurements: principle of measurements, spectrometry, common detection instrumentations, applications in nuclear engineering and R&D

A measurement of the differential pulse height spectrum from a radiation detector can yield important information on the nature of the incident radiation or the properties of the detector itself and is therefore one of the most important functions to be performed in nuclear measurements. By definition, the differential pulse height spectrum is a continuous curve that plots the value of dN/dH, the differential number of pulses observed within a differential increment of pulse height H, versus the value of the pulse height H.

The multichannel analyzer (MCA) is comprised of basic electronics components chain setup. The major task of its operation is based on the principle of converting an analog signal (the pulse amplitude) to an equivalent digital number. Then, an extensive technology available for the storage and display of the digital information provides the recording pulse height spectra. As a result, the analog to-digital converter (ADC) is a key element in determining the performance characteristics of the analyzer.

The nuclear instrumentation, mainly, based by the detector, the electronic system, the MCA and the data storage-analysis medium, can be properly adapted for several applications. Those applications are starting form the nuclear engineering instrumentation for nuclear reactors monitoring and safety, to various research instrumentations for accelerators or detector systems and so on. All these

developed to achieve this goal in Germanium, but not in Silicon. The process of Lithium ion drifting has been applied in both Silicon, Si(Li), and Germanium, Ge (Li), crystals to compensate the material after the crystal has been grown. Detectors that are manufactured from this ultrapure Germanium are usually called high purity Germanium (HPGe) detectors, and they have become available with depletion depths of several centimeters. The room-temperature operation of Germanium detectors is impossible because of the large thermally induced leakage current, due to the small band gap (1 eV). So, the Germanium detectors must be cooled to reduce the leakage current to the point that the associated noise does not spoil their excellent energy resolution. Normally, the operation temperature is at 77 K through the use of an insulated Dewar vessel, which a reservoir of liquid Nitrogen is kept in thermal contact with the detector. For Ge(Li) detectors, the low temperature must be maintained continuously to prevent a catastrophic redistribution of the drifted

The approach to obtain two-dimensional position information from a single sided silicon detector is to fabricate the top electrode as a checkerboard pattern of individual small elements that are electrically isolated from each other. If the electrode dimensions are smaller than 1 mm, the common terminology is pixel detector. Electrical connection must be made to each individual electrode and separate electronic readout channels provided for each. This approach has the advantage that the small size of each individual electrode results in a relatively small capacitance and leakage current, and thus the electronic noise is reduced considerably from that observed from microstrip detectors of equivalent dimensions. In the usual approach, a pixel detector chip is connected to a separate readout chip using flip chip solder bonding or Indium bump bonds. The readout chip is fabricated with exactly the same pitch as the detector pixels, so each bump provides an electrical connection between a single pixel and its corresponding readout electronics. Pixel detectors typically have active areas that are limited to the order of square centimeters. Larger detector areas can be achieved by assembling individual modules into arrays, although at the expense of increasing complexity in what is already a

Complicated electronic systems are adapted to get the information of the signal extraction by the radiation detectors. After an analog and digital treatment of the detector plus electronics waveform; a data acquisition system (DAQ) is accumulat-

2.6.1 Signal processing and analysis: types of electronics, signal collection and amplification, particle discrimination, spatial and time resolution

It is often desirable to change the shape of the pulse signal from radiation detectors, in some predetermined fashion. It is the most common application in processing a train of pulses produced by a preamplifier. In order to ensure that complete charge collection occurs, preamplifiers are normally adjusted to provide a decay time for the pulse, which is quite long, typically 50 μs. Depending of the rate of interaction in the detector these pulses will tend to overlap one another and give rise to a pulse train. The ideal shape is to eliminate the long tails of the pulses, but

lithium that will rapidly take place at room temperature.

Medical Imaging - Principles and Applications

2.5.4 Pixel detectors

complex device.

54

2.6 Electronics and DAQ

ing the data for further analysis and study.

experience of the nuclear instrumentation, accumulated the last decades, is implemented to the medical applications and indeed to the nuclear medical imaging techniques.

(radiopharmaceuticals) to human body assess tissue functions and to diagnose and treat properly various diseases but mainly malignant tissues. Specially designed cameras track the path of these radioactive tracers. Single Photon Emission Computed Tomography or SPECT and Positron Emission Tomography or PET scans are the two most common imaging modalities in nuclear medicine. The PET-CT scan is a combination of the PET and the CT-computed tomography, described above, which give excellent results of the cancer spots inside the body not viewed via PET or CT separately. Approved tracers are called radiopharmaceuticals since they must

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

for the approved clinical use. The proper tracer is selected to provide the most specific and reliable information for a patient's particular problem. The used tracer

The SPECT imaging scanner provides three-dimensional tomographic images of the distribution of radioactive tracer molecules that have been introduced into the patient's body. The 3D images are computer generated from a large number of projection images of the body recorded at different angles. The SPECT imagers have gamma camera detectors that can detect the gamma ray emissions from the tracers that have been injected into the patient [18]. The camera sensor detectors are mounted on a rotating gantry that allows them to be moved in a tight circle around a patient who is lying motionless on a moving bed [19]. The SPECT scans are primarily used to diagnose and track the progression of heart disease, such as blocked coronary arteries. There are also radiotracers to detect disorders in bone, gall bladder disease and intestinal tuberculosis or bleeding. The SPECT agents have recently become available for aiding in the diagnosis of Parkinson's disease in the brain, and distinguishing this disease from other anatomically related movement disorders and dementias [20]. The gamma camera has usually a set of photomultipliers on a scintillating crystal in front of which the collimator defines the image quality to be obtained, Figure 10. The collimator localizing the origin of the gamma ray forms a projection image by allowing only those gamma rays traveling in certain directions

The PET scan also uses special radiopharmaceuticals to create three-dimensional images. These radiopharmaceuticals are labeled with radioisotopes (11C, 18F, 15O or 13N) of very short life-time (minutes to few hours) and they emit positrons by their decay. The positrons are anti-particles of the electrons having positive charge. The positrons with electrons annihilate each other, in the human tissue where have been injected, emitting two gamma rays of equal energy 512 keV each in opposite directions due to the conservation of energy and momentum [20, 21]. The detectors in the PET scanner facility measure these photons emitted in time coincidence and in 180° angle. The PET camera also allows determining where they two photons are coming from, the position of the nucleus when it decayed, and also knowing where the nucleus moves inside the body. The data of the detectors obtained are processed

for providing the information to create images of internal organs or tissues.

<sup>3</sup> EMA: EUROPEAN MEDICINES AGENCY, https://www.ema.europa.eu/

<sup>2</sup> FDA: U.S. FOOD & DRUG ADMINISTRATION, https://www.fda.gov/MedicalDevices/NewsEvents/

is determined by the SPECT or PET scan to be applied to the patient [17].

<sup>3</sup> exacting standards for safety and appropriate performance

meet FDA's

4.1 SPECT imaging

<sup>2</sup> or EMA's

DOI: http://dx.doi.org/10.5772/intechopen.84356

to reach the scintillating crystal.

WorkshopsConferences/ucm429282.htm

57

4.2 PET imaging

## 3. The X-ray computed tomography imaging

The X-rays are high-energy photons produced via special vacuum tubes. The Xrays are proportionally attenuated when passing through various media; being the major advantage for the X-ray imaging. The updated medical diagnosis result of this technology is the three-dimensional (3D) X-ray computed tomography (CT), used in medical diagnosis.

#### 3.1 X-ray generation and interaction with matter

A typical X-ray tube consists of a cathode providing, by thermal emission, beam of electrons accelerated due to the anode voltage. Kinetic energy loss of the electrons at an anode is converted to X-rays. The relative position of the excited electron in the anode determines the frequency and energy of the emitted X-ray. The X-rays interact with matter in several ways, as the photon interaction mechanisms, reported in paragrap. 1.4; meaning the Photoelectric effect, Compton scattering and Pair production. The major effect in diagnostic imaging is the photoelectric effect; where an orbital electron, mainly for elements of large atomic number, absorbs the energy of an X-ray photon.

#### 3.2 CT imaging

The established X-ray imaging technique is useful for clinical diagnosis in cases of a view of the bone system. The technique offers only low soft-tissue contrast and is not very quantitative. The X-ray CT tomography relies on taking a large number of X-rays at multiple angles, getting many measurements of the incident X-ray attenuation through the plane of the human body. The attenuation measurements provide the fraction of X-ray removed in passing through a given amount of a specific material of thickness. The data obtained provide the X-ray tomography information and reconstruct a 3D image after a heavy and well elaborated data processing. The computed tomography (CT) is the method for reconstructing and providing the image of a thin cross section on the basis of measurements of X-ray attenuation. Instead, the plain film X-ray image, CT images are free of superimposing tissues and are capable of much higher contrast due to elimination of scatter. Major upgrading improvements have led to higher-resolution images, which the diagnosis process. The small size nodules or tumors can be visualized, by the CT scan, which they could not be seen with a plain X-ray film. To help soft tissues providing clear image, a special contrast material is needed to block the X-rays, in a CT scan, so highlighting blood vessels, organs, or other structures.

#### 4. The nuclear medicine SPECT, PET and PET-CT tomography imaging

Nuclear medicine is a branch of medical imaging applying non-invasive, diagnostic imaging techniques for visualization of internal organs, tissue, etc. and monitoring the functioning of them. Major modalities of imaging are the X-ray Radiography (projection), the X-ray Computed Tomography (CT) and the Nuclear Medicine (SPECT, PET and PET-CT) [15, 16]. The injected radioactive tracers

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

(radiopharmaceuticals) to human body assess tissue functions and to diagnose and treat properly various diseases but mainly malignant tissues. Specially designed cameras track the path of these radioactive tracers. Single Photon Emission Computed Tomography or SPECT and Positron Emission Tomography or PET scans are the two most common imaging modalities in nuclear medicine. The PET-CT scan is a combination of the PET and the CT-computed tomography, described above, which give excellent results of the cancer spots inside the body not viewed via PET or CT separately. Approved tracers are called radiopharmaceuticals since they must meet FDA's <sup>2</sup> or EMA's <sup>3</sup> exacting standards for safety and appropriate performance for the approved clinical use. The proper tracer is selected to provide the most specific and reliable information for a patient's particular problem. The used tracer is determined by the SPECT or PET scan to be applied to the patient [17].

#### 4.1 SPECT imaging

experience of the nuclear instrumentation, accumulated the last decades, is

3. The X-ray computed tomography imaging

Medical Imaging - Principles and Applications

3.1 X-ray generation and interaction with matter

number, absorbs the energy of an X-ray photon.

techniques.

in medical diagnosis.

3.2 CT imaging

56

implemented to the medical applications and indeed to the nuclear medical imaging

The X-rays are high-energy photons produced via special vacuum tubes. The Xrays are proportionally attenuated when passing through various media; being the major advantage for the X-ray imaging. The updated medical diagnosis result of this technology is the three-dimensional (3D) X-ray computed tomography (CT), used

A typical X-ray tube consists of a cathode providing, by thermal emission, beam of electrons accelerated due to the anode voltage. Kinetic energy loss of the electrons at an anode is converted to X-rays. The relative position of the excited electron in the anode determines the frequency and energy of the emitted X-ray. The X-rays interact with matter in several ways, as the photon interaction mechanisms, reported in paragrap. 1.4; meaning the Photoelectric effect, Compton scat-

tering and Pair production. The major effect in diagnostic imaging is the

attenuation. Instead, the plain film X-ray image, CT images are free of

superimposing tissues and are capable of much higher contrast due to elimination of scatter. Major upgrading improvements have led to higher-resolution images, which the diagnosis process. The small size nodules or tumors can be visualized, by the CT scan, which they could not be seen with a plain X-ray film. To help soft tissues providing clear image, a special contrast material is needed to block the X-rays, in a CT scan, so highlighting blood vessels, organs, or other structures.

4. The nuclear medicine SPECT, PET and PET-CT tomography imaging

Nuclear medicine is a branch of medical imaging applying non-invasive, diagnostic imaging techniques for visualization of internal organs, tissue, etc. and mon-

Radiography (projection), the X-ray Computed Tomography (CT) and the Nuclear Medicine (SPECT, PET and PET-CT) [15, 16]. The injected radioactive tracers

itoring the functioning of them. Major modalities of imaging are the X-ray

photoelectric effect; where an orbital electron, mainly for elements of large atomic

The established X-ray imaging technique is useful for clinical diagnosis in cases of a view of the bone system. The technique offers only low soft-tissue contrast and is not very quantitative. The X-ray CT tomography relies on taking a large number of X-rays at multiple angles, getting many measurements of the incident X-ray attenuation through the plane of the human body. The attenuation measurements provide the fraction of X-ray removed in passing through a given amount of a specific material of thickness. The data obtained provide the X-ray tomography information and reconstruct a 3D image after a heavy and well elaborated data processing. The computed tomography (CT) is the method for reconstructing and providing the image of a thin cross section on the basis of measurements of X-ray

The SPECT imaging scanner provides three-dimensional tomographic images of the distribution of radioactive tracer molecules that have been introduced into the patient's body. The 3D images are computer generated from a large number of projection images of the body recorded at different angles. The SPECT imagers have gamma camera detectors that can detect the gamma ray emissions from the tracers that have been injected into the patient [18]. The camera sensor detectors are mounted on a rotating gantry that allows them to be moved in a tight circle around a patient who is lying motionless on a moving bed [19]. The SPECT scans are primarily used to diagnose and track the progression of heart disease, such as blocked coronary arteries. There are also radiotracers to detect disorders in bone, gall bladder disease and intestinal tuberculosis or bleeding. The SPECT agents have recently become available for aiding in the diagnosis of Parkinson's disease in the brain, and distinguishing this disease from other anatomically related movement disorders and dementias [20]. The gamma camera has usually a set of photomultipliers on a scintillating crystal in front of which the collimator defines the image quality to be obtained, Figure 10. The collimator localizing the origin of the gamma ray forms a projection image by allowing only those gamma rays traveling in certain directions to reach the scintillating crystal.

#### 4.2 PET imaging

The PET scan also uses special radiopharmaceuticals to create three-dimensional images. These radiopharmaceuticals are labeled with radioisotopes (11C, 18F, 15O or 13N) of very short life-time (minutes to few hours) and they emit positrons by their decay. The positrons are anti-particles of the electrons having positive charge. The positrons with electrons annihilate each other, in the human tissue where have been injected, emitting two gamma rays of equal energy 512 keV each in opposite directions due to the conservation of energy and momentum [20, 21]. The detectors in the PET scanner facility measure these photons emitted in time coincidence and in 180° angle. The PET camera also allows determining where they two photons are coming from, the position of the nucleus when it decayed, and also knowing where the nucleus moves inside the body. The data of the detectors obtained are processed for providing the information to create images of internal organs or tissues.

<sup>2</sup> FDA: U.S. FOOD & DRUG ADMINISTRATION, https://www.fda.gov/MedicalDevices/NewsEvents/ WorkshopsConferences/ucm429282.htm

<sup>3</sup> EMA: EUROPEAN MEDICINES AGENCY, https://www.ema.europa.eu/

#### Figure 10.

The gamma camera setup (principle), A is the organ, and under examination, with the radiopharmaceutical compound emitting gamma rays, B is the collimator, C is the scintillating crystal and D is the array of the photomultipliers.

have the potential to provide important information to guide the biopsy of a mass to active regions of the tumor and to provide better tissue mapping [22]. The wide array of clinical applications of ionizing radiation is grouped into diagnostic and

The comparison between the CT image and the combined PET-CT image; where the avid tumor is well and

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

clearly viewed on the right image (https://www.nibib.nih.gov/) [22].

DOI: http://dx.doi.org/10.5772/intechopen.84356

The radiation dose and the diagnostic radiology procedures are of concern to the health care professions, the public, and regulators. The radiation dose depends on various factors, including the weight of the patient, the radiation sensitivity of the image tissue receptor, the energy of the radiation, the exposure rate, and the total time of radiation. Measurements of equivalent collective dose are taken for the individual patients and populations. The radiation dose from nuclear medicine procedures depends on the radiopharmaceutical, the administered activity, and individual patient metabolism. For clinical applications, dosimetry estimates of

radiopharmaceuticals are provided based on standardized adult and child metabolic and anatomic models. Recently, the use of electron accelerators as radiation source equipped with an X-ray converter is increasing. However, gamma sources are difficult to replace, especially for use with non-uniform, high-density products [24]. Fourth generation of light sources are the X-ray free electron lasers (XFELs) [25]. They provide bright bursts of X-rays, where these pulses are both spatially coherent and ultra short in duration. New techniques have been developed, including diffract-before-destruction methods; where the short X-ray pulse scatters from the sample, providing the radiation-damage-free structures measurement. They have been applied to develop a technique called serial femtosecond crystallography (SFX), where a stream of tiny protein crystals is delivered into the focus of the XFEL [26]. The Crystal Clear is an international collaboration at CERN, active on research and development on inorganic scintillation materials for novel ionizing radiation detectors, for high-energy physics, better quality medical imaging

therapeutic use [23].

Figure 11.

59

(PET-SPECT) and industrial applications [27].

The PET scan is manly used for the patients with conditions affecting the brain, heart, certain types of cancer, Alzheimer's disease and some neurological disorders. The major purpose of PET scans is to detect cancer and monitor its progression, response to treatment, and to detect metastases. Glucose utilization depends on the intensity of cellular and tissue activity so it is greatly increased in rapidly dividing cancer cells. In the last years, slightly modified radiolabeled glucose molecules (F-18 labeled deoxyglucose or FDG) have been shown to be the best available tracer for detecting cancer and its metastatic spread in the body. Different colors or degrees of brightness on a PET image represent different levels of tissue or organ function. The healthy tissues use glucose for energy, accumulating some of the tagged glucose, which will show up on the PET images. However, the tumors use more glucose than normal tissue, accumulate more of the substance and appear brighter than normal tissue on the PET images.

### 4.3 PET-CT imaging

A combination instrument that produces both PET and CT scans of the same body regions in one examination (PET/CT scanner) has become the primary imaging tool for the staging of most cancers worldwide. The images of the PET and the PET-CT combined are shown in Figure 11 [22]; where the results of the PET-CT image are extremely interesting. The incremental diagnostic value of integrated positron emission tomography-computed tomography (PET/CT) compared with PET tomography are summarized: (i) imaging quality improvement in tumors detection on both CT and PET, (ii) imaging quality improvement to the loci up taking tracer in better ratio between physiological from pathologic tissue, (iii) precise localization of the malignant foci, in various body places, i.e., bones, soft tissues, etc. (iv) improvement of spatial resolution for defining small size or unusual tumors. The use of PET/CT technique can occur at the time of initial diagnosis, in assessing the early response of disease to treatment, at the conclusion of treatment, and in continuing follow-up of patients. The PET/CT fused images

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

#### Figure 11.

The PET scan is manly used for the patients with conditions affecting the brain, heart, certain types of cancer, Alzheimer's disease and some neurological disorders. The major purpose of PET scans is to detect cancer and monitor its progression, response to treatment, and to detect metastases. Glucose utilization depends on the intensity of cellular and tissue activity so it is greatly increased in rapidly dividing cancer cells. In the last years, slightly modified radiolabeled glucose molecules (F-18 labeled deoxyglucose or FDG) have been shown to be the best available tracer for detecting cancer and its metastatic spread in the body. Different colors or degrees of brightness on a PET image represent different levels of tissue or organ function. The healthy tissues use glucose for energy, accumulating some of the tagged glucose, which will show up on the PET images. However, the tumors use more glucose than normal tissue, accumulate more of the substance and appear brighter than normal

The gamma camera setup (principle), A is the organ, and under examination, with the radiopharmaceutical compound emitting gamma rays, B is the collimator, C is the scintillating crystal and D is the array of the

A combination instrument that produces both PET and CT scans of the same body regions in one examination (PET/CT scanner) has become the primary imaging tool for the staging of most cancers worldwide. The images of the PET and the PET-CT combined are shown in Figure 11 [22]; where the results of the PET-CT image are extremely interesting. The incremental diagnostic value of integrated positron emission tomography-computed tomography (PET/CT) compared with PET tomography are summarized: (i) imaging quality improvement in tumors detection on both CT and PET, (ii) imaging quality improvement to the loci up taking tracer in better ratio between physiological from pathologic tissue, (iii) precise localization of the malignant foci, in various body places, i.e., bones, soft tissues, etc. (iv) improvement of spatial resolution for defining small size or unusual tumors. The use of PET/CT technique can occur at the time of initial diagnosis, in assessing the early response of disease to treatment, at the conclusion of treatment, and in continuing follow-up of patients. The PET/CT fused images

tissue on the PET images.

4.3 PET-CT imaging

58

Figure 10.

photomultipliers.

Medical Imaging - Principles and Applications

The comparison between the CT image and the combined PET-CT image; where the avid tumor is well and clearly viewed on the right image (https://www.nibib.nih.gov/) [22].

have the potential to provide important information to guide the biopsy of a mass to active regions of the tumor and to provide better tissue mapping [22]. The wide array of clinical applications of ionizing radiation is grouped into diagnostic and therapeutic use [23].

The radiation dose and the diagnostic radiology procedures are of concern to the health care professions, the public, and regulators. The radiation dose depends on various factors, including the weight of the patient, the radiation sensitivity of the image tissue receptor, the energy of the radiation, the exposure rate, and the total time of radiation. Measurements of equivalent collective dose are taken for the individual patients and populations. The radiation dose from nuclear medicine procedures depends on the radiopharmaceutical, the administered activity, and individual patient metabolism. For clinical applications, dosimetry estimates of radiopharmaceuticals are provided based on standardized adult and child metabolic and anatomic models. Recently, the use of electron accelerators as radiation source equipped with an X-ray converter is increasing. However, gamma sources are difficult to replace, especially for use with non-uniform, high-density products [24]. Fourth generation of light sources are the X-ray free electron lasers (XFELs) [25]. They provide bright bursts of X-rays, where these pulses are both spatially coherent and ultra short in duration. New techniques have been developed, including diffract-before-destruction methods; where the short X-ray pulse scatters from the sample, providing the radiation-damage-free structures measurement. They have been applied to develop a technique called serial femtosecond crystallography (SFX), where a stream of tiny protein crystals is delivered into the focus of the XFEL [26]. The Crystal Clear is an international collaboration at CERN, active on research and development on inorganic scintillation materials for novel ionizing radiation detectors, for high-energy physics, better quality medical imaging (PET-SPECT) and industrial applications [27].

Medical Imaging - Principles and Applications

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Wiley & Sons; 1999

Heidelberg: Springer; 1993

325-400

1954;4:315-350

2018;98:030001

1937;A15:39-41

1982

61

[1] Enge H. Introduction to Nuclear Physics. Boston: Addison-Wesley; 1972

[3] William R. Leo, Techniques fro Nuclear and Particle Physics

New York: Springer Verlag; 1994

[2] Kleinknecht K. Detectors for Particle Radiation. Cambridge UK: Cambridge

DOI: http://dx.doi.org/10.5772/intechopen.84356

[12] Marmier P, Sheldon E. Physics of Nuclei and Particles. Vol. 1. New York:

[13] Evans RD. The Atomic Nucleus. New York: McGraw-Hill; 1955

[14] Grodstein GW. X-Ray attenuation coefficients from 10 keV to 100 MeV.

[15] Hine GJ. Instrumentation in Nuclear Medicine. 1st ed. Cambridge MA:

Fundamentals of Nuclear Medicine. 2nd ed. New York: The Society of Nuclear

[18] Khoshakhlagh M et al. Development of scintillators in nuclear medicine. World Journal of Nuclear Medicine.

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Biomedical Imaging. Hoboken NJ: John

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[16] Alazraki NP, Mishkin FS.

[17] Edward L. Alpen, Radiation Biophysics. 2nd Edition. San Diego CA:

Academic Press; 1969

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging…

Academic Press; 1967

Academic Press; 1998

2015;14(3):156-159

(Supplement 2):2828

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[5] Sitar B, Merson GI, Chechin VA, Budagov YA. Ionization Measurements in High Energy Physics. Springer Tracts in Modern Physics. Vol. 124. Berlin/

[6] Bethe HA. Theorie des Durchgangs schneller Korpuskularstrahlen durch Materie. Annalen der Physik. 1930;5:

[7] Bloch F. Bremsvermogen von Atomen mit mehreren Elektronen. Zeitschrift für Physik. 1933;81:363-376

[8] Uehling EA. Penetration of heavy charged particles in matter. Annual Review of Nuclear and Particle Science.

[9] Particle Data Group. Review of particle properties. Physical Review D.

[11] Sauter E. Grundlagen des Strahlenschutzes. Berlin/München: Siemens AG; 1971. Grundlagen des Strahlenschutzes. Thiemig/München;

[10] Marshall JS, Ward AG. Absorption curves and ranges for homogeneous βrays. Canadian Journal of Research.

## Author details

Evangelos Gazis National Technical University of Athens, Athens, Greece

\*Address all correspondence to: evangelos.gazis@cern.ch

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Ionizing Radiation Interaction with Matter, the X-ray Computed Tomography Imaging… DOI: http://dx.doi.org/10.5772/intechopen.84356

## References

[1] Enge H. Introduction to Nuclear Physics. Boston: Addison-Wesley; 1972

[2] Kleinknecht K. Detectors for Particle Radiation. Cambridge UK: Cambridge University Press; 1986

[3] William R. Leo, Techniques fro Nuclear and Particle Physics Experiments. 2nd ed. Berlin, Heidelberg, New York: Springer Verlag; 1994

[4] Knoll GF. Radiation Detection and Measurement. 3rd ed. New York: John Wiley & Sons; 1999

[5] Sitar B, Merson GI, Chechin VA, Budagov YA. Ionization Measurements in High Energy Physics. Springer Tracts in Modern Physics. Vol. 124. Berlin/ Heidelberg: Springer; 1993

[6] Bethe HA. Theorie des Durchgangs schneller Korpuskularstrahlen durch Materie. Annalen der Physik. 1930;5: 325-400

[7] Bloch F. Bremsvermogen von Atomen mit mehreren Elektronen. Zeitschrift für Physik. 1933;81:363-376

[8] Uehling EA. Penetration of heavy charged particles in matter. Annual Review of Nuclear and Particle Science. 1954;4:315-350

[9] Particle Data Group. Review of particle properties. Physical Review D. 2018;98:030001

[10] Marshall JS, Ward AG. Absorption curves and ranges for homogeneous βrays. Canadian Journal of Research. 1937;A15:39-41

[11] Sauter E. Grundlagen des Strahlenschutzes. Berlin/München: Siemens AG; 1971. Grundlagen des Strahlenschutzes. Thiemig/München; 1982

[12] Marmier P, Sheldon E. Physics of Nuclei and Particles. Vol. 1. New York: Academic Press; 1969

[13] Evans RD. The Atomic Nucleus. New York: McGraw-Hill; 1955

[14] Grodstein GW. X-Ray attenuation coefficients from 10 keV to 100 MeV. National Bureau of Standards Supplement to Circular. 1957;583:1

[15] Hine GJ. Instrumentation in Nuclear Medicine. 1st ed. Cambridge MA: Academic Press; 1967

[16] Alazraki NP, Mishkin FS. Fundamentals of Nuclear Medicine. 2nd ed. New York: The Society of Nuclear Medicine; 1988

[17] Edward L. Alpen, Radiation Biophysics. 2nd Edition. San Diego CA: Academic Press; 1998

[18] Khoshakhlagh M et al. Development of scintillators in nuclear medicine. World Journal of Nuclear Medicine. 2015;14(3):156-159

[19] Fockler A, Voslar A, Guilbault J. Spatial resolution of gamma cameras for whole body bone imaging. Journal of Nuclear Medicine. 2016;57 (Supplement 2):2828

[20] Webb A. Introduction to Biomedical Imaging. Hoboken NJ: John Wiley & Sons; 2003

[21] Hendee WR, Ritenour ER. Medical Imaging Physics. 4th Edition. New York: Wiley; 2002

[22] NIBIB-National Institute of Biomedical Imagine and Bioengineering Health & Human Services. Available from: https://www.nibib.nih.gov/scie nce-education/science-topics/nuclearmedicine

Author details

Evangelos Gazis

60

National Technical University of Athens, Athens, Greece

\*Address all correspondence to: evangelos.gazis@cern.ch

provided the original work is properly cited.

Medical Imaging - Principles and Applications

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

[23] Gottfried K-LD, Penn G, editors. Radiation in Medicine, A Need For Regulatory Reform, Institute of Medicine (US) Committee for Review and Evaluation of the Medical Use Program of the Nuclear Regulatory Commission. Washington DC: National Academic Press; 1996

[24] Sun Y, Chmielewski AG. Chapter: Future developments in radiation processing. In: Applications of Ionizing Radiation in Materials Processing. 1st ed. Warszawa: Institute of Nuclear Chemistry and Technology; 2017

[25] Pellegrini C, Marinelli A, Reiche S. The physics of X-ray free-electron lasers. Reviews of Modern Physics. 2016;88:015006

[26] Martin-Garcia JM et al. Serial femtosecond crystallography: A revolution in structural biology. Archives of Biochemistry and Biophysics. 2016;602:32-47

[27] Medjoubi K et al. Performances and Applications of the CdTe- and Si-XPAD3 photon counting 2D detector. Journal of Instrumentation. 2011;6: C01080

**63**

**Chapter 4**

**Abstract**

Management

**Keywords:** lung cancer, PET-CT

**1. Lung cancer: an overview**

**1.1 Clinical features**

**1.2 Classification**

*1.2.1 Non-small cell lung cancer (NSCLC)*

PET-CT Principles and

*Long Chen, Hua Sun and Yunchao Huang*

content will benefit the clinical doctors as well as radiologists.

Applications in Lung Cancer

Lung cancer is the most common malignant cancer throughout the world; the positron emission tomography/computed tomography (PET-CT) combines both the metabolism information from PET and anatomy details from CT, which is the state of the art. This manuscript introduced the PET-CT and applications in lung cancer diagnosing, staging, and treatment. Several aspects including clinical features, classification, grading and pathology of the lung cancer, principles of PET-CT, and evaluation of diagnosing and treatment had been covered. Detailed demonstration of each cancer subtype, staging criteria, and classification was described. The

Totally lung cancer remains the first leading cause of cancer incidence and mortality, with about 2.1 million incidence and 1.8 million deaths in 2018 among 185 countries [1]. In 2018, an estimated 234,030 new cases of lung and bronchial cancer will be diagnosed, and 154,050 deaths are estimated to occur because of the disease [2]. The 5-year over survival rate is <20% once diagnosed [3]. Lung cancer is a unique disease for its etiologic agent is an addictive product cigarette, made and produced by an industry. Voluntary or involuntary (secondhand) cigarette smoking leads to nearly 90% cases, suggesting that effective public health policies to prevent initiation of smoking, oversight of tobacco products, and other tobacco control measures will play crucial roles in reducing lung cancer mortality [4]. Increased exposure to smoke from the burning of charcoal for heating and cooking is believed to contribute to the high lung cancer incidence, rather than smoking that is thought to be the leading cause of high lung cancer incidence in western countries [5].

There are four major cell types of lung cancer according to the World Health Organization (WHO) classification: adenocarcinoma (ADC), squamous cell

## **Chapter 4**

[23] Gottfried K-LD, Penn G, editors. Radiation in Medicine, A Need For Regulatory Reform, Institute of Medicine (US) Committee for Review and Evaluation of the Medical Use Program of the Nuclear Regulatory Commission. Washington DC: National

Medical Imaging - Principles and Applications

[24] Sun Y, Chmielewski AG. Chapter: Future developments in radiation processing. In: Applications of Ionizing Radiation in Materials Processing. 1st ed. Warszawa: Institute of Nuclear Chemistry and Technology; 2017

[25] Pellegrini C, Marinelli A, Reiche S. The physics of X-ray free-electron lasers. Reviews of Modern Physics.

[26] Martin-Garcia JM et al. Serial femtosecond crystallography: A revolution in structural biology. Archives of Biochemistry and Biophysics. 2016;602:32-47

[27] Medjoubi K et al. Performances and Applications of the CdTe- and Si-XPAD3 photon counting 2D detector. Journal of Instrumentation. 2011;6:

Academic Press; 1996

2016;88:015006

C01080

62

## PET-CT Principles and Applications in Lung Cancer Management

*Long Chen, Hua Sun and Yunchao Huang*

## **Abstract**

Lung cancer is the most common malignant cancer throughout the world; the positron emission tomography/computed tomography (PET-CT) combines both the metabolism information from PET and anatomy details from CT, which is the state of the art. This manuscript introduced the PET-CT and applications in lung cancer diagnosing, staging, and treatment. Several aspects including clinical features, classification, grading and pathology of the lung cancer, principles of PET-CT, and evaluation of diagnosing and treatment had been covered. Detailed demonstration of each cancer subtype, staging criteria, and classification was described. The content will benefit the clinical doctors as well as radiologists.

**Keywords:** lung cancer, PET-CT

## **1. Lung cancer: an overview**

## **1.1 Clinical features**

Totally lung cancer remains the first leading cause of cancer incidence and mortality, with about 2.1 million incidence and 1.8 million deaths in 2018 among 185 countries [1]. In 2018, an estimated 234,030 new cases of lung and bronchial cancer will be diagnosed, and 154,050 deaths are estimated to occur because of the disease [2]. The 5-year over survival rate is <20% once diagnosed [3]. Lung cancer is a unique disease for its etiologic agent is an addictive product cigarette, made and produced by an industry. Voluntary or involuntary (secondhand) cigarette smoking leads to nearly 90% cases, suggesting that effective public health policies to prevent initiation of smoking, oversight of tobacco products, and other tobacco control measures will play crucial roles in reducing lung cancer mortality [4]. Increased exposure to smoke from the burning of charcoal for heating and cooking is believed to contribute to the high lung cancer incidence, rather than smoking that is thought to be the leading cause of high lung cancer incidence in western countries [5].

### **1.2 Classification**

## *1.2.1 Non-small cell lung cancer (NSCLC)*

There are four major cell types of lung cancer according to the World Health Organization (WHO) classification: adenocarcinoma (ADC), squamous cell

carcinoma (SCC), large cell carcinoma, and small cell carcinoma [6]. The first three types are also called non-small cell lung cancer, consisting of the most majority of all lung cancers. This molecular-based classification is important for therapeutic decision-making for several reasons: (i) overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with ADC (12.6 versus 10.9 months, respectively). In contrast, in SCC patients, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/ pemetrexed (10.8 versus 9.4 months, respectively) [7]. (ii) SCC patients receiving treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) are prone to suffering from life-threatening major hemoptysis [8]. (iii) ADC patients are likely to harbor epidermal growth factor receptor (EGFR) mutations which are predictive of responsiveness to tyrosine kinase inhibitors (TKI).

Age, smoking history, previous cancer history, family history, occupational exposures, other lung diseases (chronic obstructive pulmonary disease [COPD], pulmonary fibrosis), exposure to infectious agents (e.g., endemic areas of fungal infections, tuberculosis) or risk factors, or history suggestive of infection are all potential or obvious risk factors.

#### *1.2.2 Small cell lung cancer*

Neuroendocrine tumors account for about 20% of lung cancers, and most are small cell lung cancer (SCLC) [9]. SCLC is sometimes called oat cell cancer, accounting for approximately 10–15% of lung cancers, and is considered as a separate entity from NSCLC due to its early metastases and relative response to chemotherapy and radiation. Unfortunately, although small cell lung cancer usually responds very well initially to treatment, long-term survival remains low. To be specific, the 5-year survival rate is 31% for stage I, 19% for stage II, 8% for stage IV, and only 2% for stage IV disease. There is no significant difference in the AJCC TNM staging system between NSCLC and SCLC. In fact, in addition to the TNM staging, SCLC can also be defined as "limited stage" when the tumor is encompassed within a tolerable radiation field or defined as "extensive stage" when the tumor is too large or too widespread to be encompassed within tolerable radiation field, according to the older Veterans Administration (VA) [10]. Then the NCCN Panel adopted a combined approach for staging SCLC using both the AJCC TNM staging system and the VA scheme for SCLC. In applying the TNM classifications to the VA system, the so-called limited-stage SCLC is defined as stage I to III (any T, any N, M0) which can be effectively treated with definitive radiation therapy, while extensive-stage SCLC is defined as stage IV (any T, any N, M1a/b) or T3-T4 harboring multiple lung nodules or having tumor volume that is too large to be encompassed in a tolerable radiation plan. Positron emission tomographycomputed tomography (PET-CT) scan will be useful to assess for distant metastases when limited-stage disease is suspected, and a bone scan can be performed if PET-CT is ambiguous or not available; bone biopsy can be applied if the bone scan is equivocal. Although PET-CT is superior to PET or CT alone in detecting most metastatic sites, it is inferior to MR for the detection of brain metastases [11].

#### *1.2.3 Rare carcinoma of the lung*

Adenosquamous carcinoma (ASC) is a rare subtype of lung cancer, making up 0.4–4% of all lung cancer cases, and it is made up of two of the main tumor types: adenocarcinoma and squamous [12]. People suffering from ASC are prone to survive within a shorter time than those with pure lung adenocarcinomas or squamous cell carcinomas of the lung, no matter whether it is diagnosed earlier or later. In addition, the proportion of the adenocarcinoma/squamous cell component

**65**

**Figure 1.**

*PET-CT Principles and Applications in Lung Cancer Management*

has no effect on the outcome. Cisplatin (a chemotherapy drug used in the squamous cancer cell) rather than the pemetrexed (commonly used in adenocarcinomas) tends to be more effective in the treatment of ASC. Some studies have shown that ASC has its own clinical characteristics: patients are mainly males, the average age is 68.7 years old, most patients with ASC have smoking history, and most of the diseases are located in the peripheral rather than the central segment [12].

Carcinoid tumors are a type of tumor that relates to the neuroendocrine system, accounting for about 1–6% of all lung tumors, and approximately a quarter of patients suffering from carcinoid have no symptoms at the time of discovery. Although a common X-ray or chest CT scan can detect this disease, 18F-FDG PET-CT scans are not sensitive enough to discover it or see if they have spread distantly because no obvious uptake can be discovered. Consequently, octreotide rather than

Granular cell lung tumors are extremely rare, accounting for approximately 0.2% of all lung tumors. Narrowed airways, which are caused by small, firm, and solitary nodules, can always be found. However, in most situations, this kind of disease is benign. Malignant or cancerous granular cell lung is even rarer [14].

Sarcomatoid carcinomas are another rare lung carcinoma, making up 0.3–3% of all NSCLC. Some studies have shown that heavy smoking and exposure to asbestos

Traditionally, according to histological features, NSCLC has been classified into small cell and non-small cell lung cancers and further was subdivided into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Historically, little attention was given to the differentiation of the specific subtypes because there are no therapeutic implications, especially prior to the 2004 WHO classification. Various driver mutations have been associated with these cancers over time [16]; the genetic alterations and specific protein expression level have attracted much attention (**Figure 1**).

*Classifications of lung cancer: from histology to molecular based [16] (Reprinted with permission. © 2013 by* 

*the American Society of Clinical Oncology. All rights reserved).*

FDG will be given if some are suspected of having a carcinoid tumor [13].

possibly, at least partially, are responsible for this disease [15].

**1.3 Molecular pathology of lung cancer**

*DOI: http://dx.doi.org/10.5772/intechopen.88717*

#### *PET-CT Principles and Applications in Lung Cancer Management DOI: http://dx.doi.org/10.5772/intechopen.88717*

*Medical Imaging - Principles and Applications*

potential or obvious risk factors.

*1.2.2 Small cell lung cancer*

carcinoma (SCC), large cell carcinoma, and small cell carcinoma [6]. The first three types are also called non-small cell lung cancer, consisting of the most majority of all lung cancers. This molecular-based classification is important for therapeutic decision-making for several reasons: (i) overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with ADC (12.6 versus 10.9 months, respectively). In contrast, in SCC patients, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/ pemetrexed (10.8 versus 9.4 months, respectively) [7]. (ii) SCC patients receiving treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) are prone to suffering from life-threatening major hemoptysis [8]. (iii) ADC patients are likely to harbor epidermal growth factor receptor (EGFR) mutations which are

Age, smoking history, previous cancer history, family history, occupational exposures, other lung diseases (chronic obstructive pulmonary disease [COPD], pulmonary fibrosis), exposure to infectious agents (e.g., endemic areas of fungal infections, tuberculosis) or risk factors, or history suggestive of infection are all

Neuroendocrine tumors account for about 20% of lung cancers, and most are small cell lung cancer (SCLC) [9]. SCLC is sometimes called oat cell cancer, accounting for approximately 10–15% of lung cancers, and is considered as a separate entity from NSCLC due to its early metastases and relative response to chemotherapy and radiation. Unfortunately, although small cell lung cancer usually responds very well initially to treatment, long-term survival remains low. To be specific, the 5-year survival rate is 31% for stage I, 19% for stage II, 8% for stage IV, and only 2% for stage IV disease. There is no significant difference in the AJCC TNM staging system between NSCLC and SCLC. In fact, in addition to the TNM staging, SCLC can also be defined as "limited stage" when the tumor is encompassed within a tolerable radiation field or defined as "extensive stage" when the tumor is too large or too widespread to be encompassed within tolerable radiation field, according to the older Veterans Administration (VA) [10]. Then the NCCN Panel adopted a combined approach for staging SCLC using both the AJCC TNM staging system and the VA scheme for SCLC. In applying the TNM classifications to the VA system, the so-called limited-stage SCLC is defined as stage I to III (any T, any N, M0) which can be effectively treated with definitive radiation therapy, while extensive-stage SCLC is defined as stage IV (any T, any N, M1a/b) or T3-T4 harboring multiple lung nodules or having tumor volume that is too large to be encompassed in a tolerable radiation plan. Positron emission tomographycomputed tomography (PET-CT) scan will be useful to assess for distant metastases when limited-stage disease is suspected, and a bone scan can be performed if PET-CT is ambiguous or not available; bone biopsy can be applied if the bone scan is equivocal. Although PET-CT is superior to PET or CT alone in detecting most metastatic sites, it is

predictive of responsiveness to tyrosine kinase inhibitors (TKI).

inferior to MR for the detection of brain metastases [11].

Adenosquamous carcinoma (ASC) is a rare subtype of lung cancer, making up 0.4–4% of all lung cancer cases, and it is made up of two of the main tumor types: adenocarcinoma and squamous [12]. People suffering from ASC are prone to survive within a shorter time than those with pure lung adenocarcinomas or squamous cell carcinomas of the lung, no matter whether it is diagnosed earlier or later. In addition, the proportion of the adenocarcinoma/squamous cell component

*1.2.3 Rare carcinoma of the lung*

**64**

has no effect on the outcome. Cisplatin (a chemotherapy drug used in the squamous cancer cell) rather than the pemetrexed (commonly used in adenocarcinomas) tends to be more effective in the treatment of ASC. Some studies have shown that ASC has its own clinical characteristics: patients are mainly males, the average age is 68.7 years old, most patients with ASC have smoking history, and most of the diseases are located in the peripheral rather than the central segment [12].

Carcinoid tumors are a type of tumor that relates to the neuroendocrine system, accounting for about 1–6% of all lung tumors, and approximately a quarter of patients suffering from carcinoid have no symptoms at the time of discovery. Although a common X-ray or chest CT scan can detect this disease, 18F-FDG PET-CT scans are not sensitive enough to discover it or see if they have spread distantly because no obvious uptake can be discovered. Consequently, octreotide rather than FDG will be given if some are suspected of having a carcinoid tumor [13].

Granular cell lung tumors are extremely rare, accounting for approximately 0.2% of all lung tumors. Narrowed airways, which are caused by small, firm, and solitary nodules, can always be found. However, in most situations, this kind of disease is benign. Malignant or cancerous granular cell lung is even rarer [14].

Sarcomatoid carcinomas are another rare lung carcinoma, making up 0.3–3% of all NSCLC. Some studies have shown that heavy smoking and exposure to asbestos possibly, at least partially, are responsible for this disease [15].

#### **1.3 Molecular pathology of lung cancer**

Traditionally, according to histological features, NSCLC has been classified into small cell and non-small cell lung cancers and further was subdivided into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Historically, little attention was given to the differentiation of the specific subtypes because there are no therapeutic implications, especially prior to the 2004 WHO classification. Various driver mutations have been associated with these cancers over time [16]; the genetic alterations and specific protein expression level have attracted much attention (**Figure 1**).

#### **Figure 1.**

*Classifications of lung cancer: from histology to molecular based [16] (Reprinted with permission. © 2013 by the American Society of Clinical Oncology. All rights reserved).*

## **1.4 TNM staging**

The primary tumor (T), regional lymph node involvement (N), and distant metastasis (M) are the bases of staging for lung cancer. The International Association Society of Lung Cancer (IASLC) recommends the TNM classification of malignant tumors published by the Union Internationale Contre Le Cancer (UICC) and the American Joint Committee on Cancer (AJCC), and the latest eighth edition was published in 2016 [17]. Based on the different T, N, and M combinations, patients are grouped into different stages, which will determine the clinical treatments and can also predict various prognoses. The staging system is described in **Table 1**, and the stage groupings based on the TNM are listed in **Table 2**.


**67**

**Table 2.**

**1.5 Synoptic reporting of lung cancer**

*Stage groupings in the eighth edition of TNM staging system for lung cancer.*

Synoptic reporting for lung cancer aimed to standardize diagnostic reports, including recommended clinical and histopathologic variables. This includes the

*PET-CT Principles and Applications in Lung Cancer Management*

or supraclavicular lymph node(s)

N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension

N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene,

M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules

related to the tumor, the effusion should be excluded as a staging descriptor

M1b Single extrathoracic metastasis in a single organ (including involvement of a single

**Stage group T N M** Stage IA T1 N0 M0 Stage IA1 T1mi, T1a N0 M0 Stage IA2 T1b N0 M0 Stage IA3 T1c N0 M0 Stage IB T2a N0 M0 Stage IIA T2b N0 M0 Stage IIB T1a-c, T2a, b N1 M0

Stage IIIA T1a-c, T2a, b N2 M0

Stage IIIB T1a-c, T2a, b N3 M0

Stage IIIC T3, T4 N3 M0 Stage IVA Any T Any N M1a, b Stage IVB Any T Any N M1c

T3 N0 M0

T3 N1 M0 T4 N0, N1 M0

T3, T4 N2 M0

M1c Multiple extrathoracic metastases in a single organ or in multiple organs

or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not

N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)

*DOI: http://dx.doi.org/10.5772/intechopen.88717*

M criteria

nonregional node)

M0 No distant metastasis M1 Distant metastasis

*The eighth edition of TNM for lung cancer.*

M category

**Table 1.**

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis

#### *PET-CT Principles and Applications in Lung Cancer Management DOI: http://dx.doi.org/10.5772/intechopen.88717*


#### **Table 1.**

*Medical Imaging - Principles and Applications*

T0 No evidence of primary tumor

dimension

main bronchus)

T1b Tumor >1 cm but ≤2 cm in greatest dimension T1c Tumor >2 cm but ≤3 cm in greatest dimension

ment of the carina

T2a Tumor >3 cm but ≤4 cm in greatest dimension T2b Tumor >4 cm but ≤5 cm in greatest dimension

T2 Tumor >3 cm but ≤5 cm or having any of the following features:

• Invades visceral pleura (PL1 or PL2)

involving part or all of the lung

and T2b if >4 cm but ≤5 cm in greatest dimension

T3 Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following:

pericardium; or separate tumor nodule (s) in the same lobe as the primary T4 Tumor >7 cm or tumor of any size invading one or more of the following: the diaphragm,

Squamous cell carcinoma in situ (SCIS)

Tis Carcinoma in situ

The primary tumor (T), regional lymph node involvement (N), and distant metastasis (M) are the bases of staging for lung cancer. The International Association Society of Lung Cancer (IASLC) recommends the TNM classification of malignant tumors published by the Union Internationale Contre Le Cancer (UICC) and the American Joint Committee on Cancer (AJCC), and the latest eighth edition was published in 2016 [17]. Based on the different T, N, and M combinations, patients are grouped into different stages, which will determine the clinical treatments and can also predict various prognoses. The staging system is described

in **Table 1**, and the stage groupings based on the TNM are listed in **Table 2**.

Tx Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy

T1 Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without

bronchus; also is classified as T1a, but these tumors are uncommon

T1mi Minimally invasive adenocarcinoma: adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤ 5 mm invasion in greatest dimension T1a Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose

Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, ≤3 cm in greatest

bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the

invasive component is limited to the bronchial wall and may extend proximal to the main

• Involves the main bronchus regardless of distance to the carina, but without involve-

• Associated with atelectasis or obstructive pneumonitis that extends to the hilar region,

T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined

parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal

mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary

**1.4 TNM staging**

T—Primary tumor T category T criteria

**66**

N—Regional lymph N category N criteria *The eighth edition of TNM for lung cancer.*


#### **Table 2.**

*Stage groupings in the eighth edition of TNM staging system for lung cancer.*

## **1.5 Synoptic reporting of lung cancer**

Synoptic reporting for lung cancer aimed to standardize diagnostic reports, including recommended clinical and histopathologic variables. This includes the


**69**

*PET-CT Principles and Applications in Lung Cancer Management*

**2.1 Surgical management of primary lung cancer**

treatment of incurable NSCLC patients [21–23].

**2.3 Immunotherapy and targeted therapy**

clinical details and macroscopic, microscopic, and pathological staging as essential requirements. In addition, there should be an assessment of lymphovascular invasion and neurotropism and the presence of absence of satellite lesions; all these are

Generally speaking, surgery is the best chance for stage I or II lung cancer patients [18]. Surgical oncology consultation is necessary for any patient being considered for local therapy. The general treatment plan, the essential imaging studies, and laboratory results should be determined before any nonemergency treatment is started. If patients cannot tolerate surgery or are inoperable, minimally invasive techniques, such as sublobar resection, can be a better choice [19]. Selected patients, including those who are not eligible for lobectomy and those with a peripheral nodule 2 cm or less with very low-risk features, are recommended to go through sublobar resection, either segmentectomy (preferred) or wedge resection. On the other hand, segmentectomy (preferred) or wedge resection should achieve parenchymal resection margins that are (1) 2 cm or more or (2) the size of the

The principles of radiation therapy in the NSCLC algorithm has been described

Specific targeted therapies can be used to treat advanced NSCLC. Bevacizumab

is a monoclonal antibody, targeting vascular endothelial growth factor, while ramucirumab is a recombinant monoclonal antibody that targets VEGF receptors. Cetuximab is a monoclonal antibody that targets EGFR. Erlotinib, gefitinib, and afatinib inhibit EGFR-sensitizing mutations; osimertinib inhibits both EGFR-sensitizing mutations and T790 M. ALK rearrangement, ROS1 rearrangement, and MET were all inhibited by crizotinib. Patients with ALK rearrangement are recommended to ceritinib which inhibits the IGF-1 receptor. Alectinib inhibits ALK and RET rearrangement. Brigatinib inhibits various ALK rearrangements and other targets. Dabrafenib/ trametinib inhibits the BRAF V600E mutation; trametinib also inhibits MEK; both drugs inhibit different kinases in the RAS/RAF/MEK/ERK pathway [24, 25].

thoroughly, including the following: general principles for early-stage, locally advanced, and advanced NSCLC; target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced NSCLC; and RT simulation, planning, and delivery [20]. Treatment recommendations should be made by a multidisciplinary team. Because of the potential role of radiotherapy in all stages of NSCLC, whether it is a definitive treatment or palliative treatment is not known. Radiotherapy uses for NSCLC include, but are not limited to, (1) definitive treatment of locally advanced NSCLC, usually combined with chemotherapy; (2) definitive treatment of early NSCLC in patients with surgical contraindications; (3) partial preoperative or postoperative treatment of surgical patients; (4) treatment of limited recurrence and metastasis; and/or (5) palliative

*DOI: http://dx.doi.org/10.5772/intechopen.88717*

**2. Management of lung cancer**

shown in **Table 3**.

nodule or more.

**2.2 Radiotherapy**

Residual tumor status Completeness of surgical resection Diagnostic summary

#### **Table 3.**

*Synoptic reporting of lung cancer.*

clinical details and macroscopic, microscopic, and pathological staging as essential requirements. In addition, there should be an assessment of lymphovascular invasion and neurotropism and the presence of absence of satellite lesions; all these are shown in **Table 3**.

## **2. Management of lung cancer**

*Medical Imaging - Principles and Applications*

Clinical information provided on request

Details of previous cancer diagnosis

New primary cancer or recurrence Pathology accession number

Attached anatomical structures Accompanying specimens Block identification key

Maximum tumor dimension

*Site(s) and number of lymph nodes* Atelectasis/obstructive pneumonitis

Other relevant information and comments

Pathological staging (AJCC seventh edition)

Macroscopic appearance of pleura overlying tumor Extent of direct spread of tumor to other tissues Distance of tumor to closest resection margin Tumor involves main bronchus within 20 mm of carina

Principal clinician caring for the patient Other clinical information received

Results of previous cytological investigations or biopsies Details of any previous treatment of the current tumor

Risk factors for lung cancer (e.g., smoking history, ethnicity, and asbestos exposure)

Nature of the resection Additional extrapulmonary tissue Site and laterality of tumor

Clinical tumor stage

Macroscopic Operative procedure Specimen laterality

Tumor site Tumor location Separate tumor nodules *Number of tumors*

*Site*

Lymph nodes

*Extent* Nonneoplastic lung

Microscopic

Suffixes

Primary tumor (T) Regional lymph nodes (N) Distant metastasis (M) Residual tumor status

Diagnostic summary

*Synoptic reporting of lung cancer.*

Completeness of surgical resection

Histological tumor type *Adenocarcinoma classification*

Histological grade Visceral pleural invasion *Extent of pleural involvement* Lymphovascular invasion *Vessel(s) involved Type of involvement* Perineural invasion

**Terms** Clinical details

**68**

**Table 3.**

## **2.1 Surgical management of primary lung cancer**

Generally speaking, surgery is the best chance for stage I or II lung cancer patients [18]. Surgical oncology consultation is necessary for any patient being considered for local therapy. The general treatment plan, the essential imaging studies, and laboratory results should be determined before any nonemergency treatment is started. If patients cannot tolerate surgery or are inoperable, minimally invasive techniques, such as sublobar resection, can be a better choice [19]. Selected patients, including those who are not eligible for lobectomy and those with a peripheral nodule 2 cm or less with very low-risk features, are recommended to go through sublobar resection, either segmentectomy (preferred) or wedge resection. On the other hand, segmentectomy (preferred) or wedge resection should achieve parenchymal resection margins that are (1) 2 cm or more or (2) the size of the nodule or more.

## **2.2 Radiotherapy**

The principles of radiation therapy in the NSCLC algorithm has been described thoroughly, including the following: general principles for early-stage, locally advanced, and advanced NSCLC; target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced NSCLC; and RT simulation, planning, and delivery [20]. Treatment recommendations should be made by a multidisciplinary team. Because of the potential role of radiotherapy in all stages of NSCLC, whether it is a definitive treatment or palliative treatment is not known. Radiotherapy uses for NSCLC include, but are not limited to, (1) definitive treatment of locally advanced NSCLC, usually combined with chemotherapy; (2) definitive treatment of early NSCLC in patients with surgical contraindications; (3) partial preoperative or postoperative treatment of surgical patients; (4) treatment of limited recurrence and metastasis; and/or (5) palliative treatment of incurable NSCLC patients [21–23].

## **2.3 Immunotherapy and targeted therapy**

Specific targeted therapies can be used to treat advanced NSCLC. Bevacizumab is a monoclonal antibody, targeting vascular endothelial growth factor, while ramucirumab is a recombinant monoclonal antibody that targets VEGF receptors. Cetuximab is a monoclonal antibody that targets EGFR. Erlotinib, gefitinib, and afatinib inhibit EGFR-sensitizing mutations; osimertinib inhibits both EGFR-sensitizing mutations and T790 M. ALK rearrangement, ROS1 rearrangement, and MET were all inhibited by crizotinib. Patients with ALK rearrangement are recommended to ceritinib which inhibits the IGF-1 receptor. Alectinib inhibits ALK and RET rearrangement. Brigatinib inhibits various ALK rearrangements and other targets. Dabrafenib/ trametinib inhibits the BRAF V600E mutation; trametinib also inhibits MEK; both drugs inhibit different kinases in the RAS/RAF/MEK/ERK pathway [24, 25].

## **3. Role of PET-CT in lung cancer**

## **3.1 Principles of PET-CT**

PET-CT is a nuclear medicine technique that combines a positron emission tomography (PET) scanner with an X-ray computed tomography (CT) scanner. The anatomical imaging obtained by CT scan and the functional imaging obtained by PET (which depicts the spatial distribution of metabolic or biochemical activity in vivo) can achieve the same machine fusion more accurately, and the generated fusion image can be based on general software and control system to obtain 2D and 3D image reconstruction. Previously pure PET imaging cannot provide accurate anatomical positioning, and thus its value was limited, while PET-CT revolutionized medical diagnosis in many areas by increasing the accuracy of anatomical positioning in functional imaging. For example, the diagnosis and classification of benign and malignant tumors, the development of surgical plans, and the delineation of radiotherapy target areas have rapidly changed under the influence of PET-CT availability [26]. PET-CT-based grading staging has significantly changed clinical decisions; so many hospitals' nuclear medicine departments have gradually reduced the usage of traditional PET devices and replaced them with PET-CT. One of the barriers to the wider use of PET-CT is its relatively expensive price. Another obstacle is the difficulty and cost of producing and transporting of radiopharmaceuticals for PET imaging, which usually have a short half-life (e.g., radioactive fluorine-18). The half-life of (18F) is used to track glucose metabolism (using fluorodeoxyglucose (FDG)) for only 106 minutes, and its production requires very expensive cyclotrons and radiopharmaceutical production lines [27].

#### **3.2 Preoperative staging**

Identifying the stage of lung cancer not only helps determine the appropriate treatment but also is essential for prognosis. Incorrect staging of lung cancer can lead to mistaken resections of benign nodules and early local or distant relapse after surgery with curative intent. Barbara randomly assigned patients referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone followed until death or for at least 12 months. They defined ineffective thoracotomy as any of the following: thoracotomy, pathologically confirmed mediastinal lymph node involvement (stage IIIA [N2]), stage IIIB or IV disease, or benign lung disease; exploratory thoracic incision; or thoracotomy in patients who have relapsed or died for any reason within 1 year after randomization. Ninety-eight patients were assigned to the PET-CT group and 91 to the conventional staging group. Sixty patients in the PET-CT group and 73 in the conventional staging group underwent thoracotomy (P = 0.004). Among these thoracotomies, 21 in the PET-CT group and 38 in the conventional staging group were futile (P = 0.05). Both groups had a reasonable thoracotomy and had similar survival. The use of PET-CT in the preoperative staging of NSCLC reduced the total number of thoracotomy and the number of ineffective thoracotomy, but did not affect overall mortality [28] (**Figure 2**).

#### **3.3 Evaluation of treatment effect**

Franco et al. conducted research aiming to evaluate the utility between PET-CT and the contrast-enhanced (CE) CT. The low-dose CT scans were performed for attenuation correction of the PET images, and the PET scanner was fully crosscalibrated, allowing accurate standard uptake value measurements. The protocols

**71**

lung cancer [29].

**Figure 2.**

**3.4 Surveillance**

**3.5 Guiding biopsy**

*PET-CT Principles and Applications in Lung Cancer Management*

for CE-CT are the following: (1) all chest CT scans were performed according to the conventional low-dose chest multi-detection CT protocol, including headto-tail orientation, arms raised on the head, single breath, and the amount of scan from the diaphragm level to the level directly above the chest entrance; and (2) the injected volume of contrast medium was tailored to the individual body weight: 60 mL at 2 mL/s for <50 kg or 80 mL at 2.5 mL/s at 50 kg or heavier with a fixed contrast delay of 35 seconds. The study enrolled 96 patients who received curative-intent treatment, and the results showed that the sensitivity, specificity, and positive predictive value for detecting cancer recurrence (95% confidence interval) were 0.88, 0.62, and 0.56 for PET-CT and 0.93, 0.72, and 0.64 for CE-CT, respectively, indicating that PET-CT is not superior to CE-CT in detecting cancer recurrence during 2 years after curative-intent treatment of non-small cell

*Preoperative staging of NSCLC between PET-CT group and conventional staging group.*

Using systematic review and meta-analysis, Nie et al. evaluated the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for small cell lung cancer and used the pooled hazard ratio (HR) to measure the influence of MTV and TLG on survival. They found that patients with high MTV are associated with a significantly poorer prognosis OS and PFS, while high TLG is associated with

When lung cancer is discovered, accurate staging at baseline is necessary to maximize patient benefit and cost-effective use of healthcare resources. Although CT remains a powerful tool for the staging of lung cancer, advances in combined imaging modalities, specifically PET-CT, have improved the baseline staging accuracy over that of CT alone [31]. FDG PET-CT has been considered a "metabolic biopsy" tool in the evaluation of nonlung lesions with indeterminate biopsy results [32]. PET-CT data coregistered with intraprocedural CT images could guide needle placement in the viable portion of the lesion and thus increase the chances of achieving a definitive diagnosis and CT-guided, fine-needle aspiration (FNA) biopsies performed with FDG PET scans of pulmonary lesions contributing sub-

stantially to the management and treatment of pulmonary disease [33].

a significantly poorer prognosis regarding OS for SCLC [30].

*DOI: http://dx.doi.org/10.5772/intechopen.88717*

*PET-CT Principles and Applications in Lung Cancer Management DOI: http://dx.doi.org/10.5772/intechopen.88717*

#### **Figure 2.**

*Medical Imaging - Principles and Applications*

**3. Role of PET-CT in lung cancer**

PET-CT is a nuclear medicine technique that combines a positron emission tomography (PET) scanner with an X-ray computed tomography (CT) scanner. The anatomical imaging obtained by CT scan and the functional imaging obtained by PET (which depicts the spatial distribution of metabolic or biochemical activity in vivo) can achieve the same machine fusion more accurately, and the generated fusion image can be based on general software and control system to obtain 2D and 3D image reconstruction. Previously pure PET imaging cannot provide accurate anatomical positioning, and thus its value was limited, while PET-CT revolutionized medical diagnosis in many areas by increasing the accuracy of anatomical positioning in functional imaging. For example, the diagnosis and classification of benign and malignant tumors, the development of surgical plans, and the delineation of radiotherapy target areas have rapidly changed under the influence of PET-CT availability [26]. PET-CT-based grading staging has significantly changed clinical decisions; so many hospitals' nuclear medicine departments have gradually reduced the usage of traditional PET devices and replaced them with PET-CT. One of the barriers to the wider use of PET-CT is its relatively expensive price. Another obstacle is the difficulty and cost of producing and transporting of radiopharmaceuticals for PET imaging, which usually have a short half-life (e.g., radioactive fluorine-18). The half-life of (18F) is used to track glucose metabolism (using fluorodeoxyglucose (FDG)) for only 106 minutes, and its production requires very

expensive cyclotrons and radiopharmaceutical production lines [27].

Identifying the stage of lung cancer not only helps determine the appropriate treatment but also is essential for prognosis. Incorrect staging of lung cancer can lead to mistaken resections of benign nodules and early local or distant relapse after surgery with curative intent. Barbara randomly assigned patients referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone followed until death or for at least 12 months. They defined ineffective thoracotomy as any of the following: thoracotomy, pathologically confirmed mediastinal lymph node involvement (stage IIIA [N2]), stage IIIB or IV disease, or benign lung disease; exploratory thoracic incision; or thoracotomy in patients who have relapsed or died for any reason within 1 year after randomization. Ninety-eight patients were assigned to the PET-CT group and 91 to the conventional staging group. Sixty patients in the PET-CT group and 73 in the conventional staging group underwent thoracotomy (P = 0.004). Among these thoracotomies, 21 in the PET-CT group and 38 in the conventional staging group were futile (P = 0.05). Both groups had a reasonable thoracotomy and had similar survival. The use of PET-CT in the preoperative staging of NSCLC reduced the total number of thoracotomy and the number of ineffective thoracotomy, but did not

Franco et al. conducted research aiming to evaluate the utility between PET-CT and the contrast-enhanced (CE) CT. The low-dose CT scans were performed for attenuation correction of the PET images, and the PET scanner was fully crosscalibrated, allowing accurate standard uptake value measurements. The protocols

**3.1 Principles of PET-CT**

**3.2 Preoperative staging**

affect overall mortality [28] (**Figure 2**).

**3.3 Evaluation of treatment effect**

**70**

*Preoperative staging of NSCLC between PET-CT group and conventional staging group.*

for CE-CT are the following: (1) all chest CT scans were performed according to the conventional low-dose chest multi-detection CT protocol, including headto-tail orientation, arms raised on the head, single breath, and the amount of scan from the diaphragm level to the level directly above the chest entrance; and (2) the injected volume of contrast medium was tailored to the individual body weight: 60 mL at 2 mL/s for <50 kg or 80 mL at 2.5 mL/s at 50 kg or heavier with a fixed contrast delay of 35 seconds. The study enrolled 96 patients who received curative-intent treatment, and the results showed that the sensitivity, specificity, and positive predictive value for detecting cancer recurrence (95% confidence interval) were 0.88, 0.62, and 0.56 for PET-CT and 0.93, 0.72, and 0.64 for CE-CT, respectively, indicating that PET-CT is not superior to CE-CT in detecting cancer recurrence during 2 years after curative-intent treatment of non-small cell lung cancer [29].

#### **3.4 Surveillance**

Using systematic review and meta-analysis, Nie et al. evaluated the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for small cell lung cancer and used the pooled hazard ratio (HR) to measure the influence of MTV and TLG on survival. They found that patients with high MTV are associated with a significantly poorer prognosis OS and PFS, while high TLG is associated with a significantly poorer prognosis regarding OS for SCLC [30].

#### **3.5 Guiding biopsy**

When lung cancer is discovered, accurate staging at baseline is necessary to maximize patient benefit and cost-effective use of healthcare resources. Although CT remains a powerful tool for the staging of lung cancer, advances in combined imaging modalities, specifically PET-CT, have improved the baseline staging accuracy over that of CT alone [31]. FDG PET-CT has been considered a "metabolic biopsy" tool in the evaluation of nonlung lesions with indeterminate biopsy results [32]. PET-CT data coregistered with intraprocedural CT images could guide needle placement in the viable portion of the lesion and thus increase the chances of achieving a definitive diagnosis and CT-guided, fine-needle aspiration (FNA) biopsies performed with FDG PET scans of pulmonary lesions contributing substantially to the management and treatment of pulmonary disease [33].

## **4. PET-CT in lung cancer: teaching cases**

## **4.1 Adenocarcinoma**

Teaching point: adenocarcinoma mainly located in the peripheral segment and shows higher FDG uptake (**Figure 3**).

## **4.2 SCC**

Teaching point: adenocarcinoma is mainly located in the central segment and shows moderate FDG uptake (**Figure 4**).

## **4.3 Large cell lung cancer**

Teaching point: large cell lung cancer always shows moderate FDG uptake and diffused distribution (**Figure 5**).

## **4.4 Small cell lung cancer**

Teaching point: small cell lung cancer shows a small mass with moderate FDG uptake (**Figure 6**).

#### **Figure 3.**

*Axial PET, CT, PET-CT, and MIP images in a patient of adenocarcinoma. An irregular mass showing higher FDG uptake in the lesion was discovered in the anterior segment of the right upper lobar.*

**73**

**Figure 5.**

*lymph node in the mediastinum.*

**Figure 4.**

*around the malignant lung lesion.*

*PET-CT Principles and Applications in Lung Cancer Management*

*Axial PET, CT, PET-CT, and MIP images in a patient of squamous cell carcinoma. An irregular mass showing moderate FDG uptake in the lesion was discovered in the central segment of the right lung, with inflammation* 

*Axial PET, CT, PET-CT, and MIP images in a patient of large cell cancer. Multisite masses showing higher FDG uptake in the lesion were discovered in the left and right lung field, with inflammation and enlarged* 

*DOI: http://dx.doi.org/10.5772/intechopen.88717*

*PET-CT Principles and Applications in Lung Cancer Management DOI: http://dx.doi.org/10.5772/intechopen.88717*

#### **Figure 4.**

*Medical Imaging - Principles and Applications*

shows higher FDG uptake (**Figure 3**).

shows moderate FDG uptake (**Figure 4**).

**4.1 Adenocarcinoma**

**4.3 Large cell lung cancer**

**4.4 Small cell lung cancer**

uptake (**Figure 6**).

diffused distribution (**Figure 5**).

**4.2 SCC**

**4. PET-CT in lung cancer: teaching cases**

Teaching point: adenocarcinoma mainly located in the peripheral segment and

Teaching point: adenocarcinoma is mainly located in the central segment and

Teaching point: large cell lung cancer always shows moderate FDG uptake and

Teaching point: small cell lung cancer shows a small mass with moderate FDG

**72**

**Figure 3.**

*Axial PET, CT, PET-CT, and MIP images in a patient of adenocarcinoma. An irregular mass showing higher* 

*FDG uptake in the lesion was discovered in the anterior segment of the right upper lobar.*

*Axial PET, CT, PET-CT, and MIP images in a patient of squamous cell carcinoma. An irregular mass showing moderate FDG uptake in the lesion was discovered in the central segment of the right lung, with inflammation around the malignant lung lesion.*

#### **Figure 5.**

*Axial PET, CT, PET-CT, and MIP images in a patient of large cell cancer. Multisite masses showing higher FDG uptake in the lesion were discovered in the left and right lung field, with inflammation and enlarged lymph node in the mediastinum.*

#### **Figure 6.**

*Axial PET, CT, PET-CT, and MIP images in a patient of small cell lung cancer. Small mass located in the right hilar with slight FDG uptake in the lesion was discovered in the right lung field.*

#### **5. Conclusions**

The current chapter focused on the PET-CT utility in lung cancer diagnosis and summarized the basic clinic utilities, including guiding to select the biopsy site, improving target delineation accuracy, evaluating disease progression on first-line therapy, and detecting hilar, mediastinal nodes and metastatic disease. PET-CT scans have been widely used to help evaluate the extent of disease and to provide more accurate staging and has been recommended by the NCCN. Patients with suspected malignant lung nodules should be scanned by PET-CT for accurate diagnosis of local or distant metastasis.

#### **Acknowledgements**

This work is supported by China Postdoctoral Science Foundation (No. 2019M653501), Initiation Foundation for Doctors of Yunnan Cancer Hospital (No. BSKY201706), Joint Special Fund from Yunnan Provincial Science and Technology Department-Kunming Medical University for Applied and Basic

**75**

**Author details**

, Hua Sun1

and Yunchao Huang2

Xishan District, Kunming, Yunnan, People's Republic of China

Xishan District, Kunming, Yunnan, People's Republic of China

\*Address all correspondence to: huangyunch2017@126.com

provided the original work is properly cited.

\*

1 Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province,

2 Department of Thoracic Surgery I, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Long Chen1

*PET-CT Principles and Applications in Lung Cancer Management*

Research (No. 2018FE001-150), the National Natural Science Foundation of China (No. 81960496) and the 100 Young and Middle-aged Academic and Technical Backbone Incubation Projects of Kunming Medical University.

*DOI: http://dx.doi.org/10.5772/intechopen.88717*

*PET-CT Principles and Applications in Lung Cancer Management DOI: http://dx.doi.org/10.5772/intechopen.88717*

Research (No. 2018FE001-150), the National Natural Science Foundation of China (No. 81960496) and the 100 Young and Middle-aged Academic and Technical Backbone Incubation Projects of Kunming Medical University.

## **Author details**

*Medical Imaging - Principles and Applications*

**74**

**5. Conclusions**

**Figure 6.**

of local or distant metastasis.

**Acknowledgements**

The current chapter focused on the PET-CT utility in lung cancer diagnosis and summarized the basic clinic utilities, including guiding to select the biopsy site, improving target delineation accuracy, evaluating disease progression on first-line therapy, and detecting hilar, mediastinal nodes and metastatic disease. PET-CT scans have been widely used to help evaluate the extent of disease and to provide more accurate staging and has been recommended by the NCCN. Patients with suspected malignant lung nodules should be scanned by PET-CT for accurate diagnosis

*Axial PET, CT, PET-CT, and MIP images in a patient of small cell lung cancer. Small mass located in the right* 

*hilar with slight FDG uptake in the lesion was discovered in the right lung field.*

This work is supported by China Postdoctoral Science Foundation (No. 2019M653501), Initiation Foundation for Doctors of Yunnan Cancer Hospital (No. BSKY201706), Joint Special Fund from Yunnan Provincial Science and Technology Department-Kunming Medical University for Applied and Basic

Long Chen1 , Hua Sun1 and Yunchao Huang2 \*

1 Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Xishan District, Kunming, Yunnan, People's Republic of China

2 Department of Thoracic Surgery I, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Xishan District, Kunming, Yunnan, People's Republic of China

\*Address all correspondence to: huangyunch2017@126.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[25] Giaccone G. Epidermal growth factor receptor inhibitors in the treatment of non-small-cell lung cancer. Journal of Clinical Oncology. 2005;**23**(14):3235-3242

[26] Shao H, Ma X, Gao Y, Wang J, Wu J, Wang B, et al. Comparison of the diagnostic efficiency for local recurrence of rectal cancer using CT, MRI, PET and PET-CT: A systematic review protocol. Medicine (Baltimore). 2018;**97**(48):e12900

[27] Bertagna F, Albano D, Giovanella L, Giubbini R, Treglia G. F18-choline/C11 choline PET/CT thyroid incidentalomas. Endocrine. 2019;**64**(2):203-208

[28] Fischer B, Lassen U, Mortensen J, Larsen S, Loft A, Bertelsen A, et al. Preoperative staging of lung cancer with combined PET-CT. The New England Journal of Medicine. 2009;**361**(1):32-39

[29] Gambazzi F, Frey LD, Bruehlmeier M, Janthur WD, Graber SM, Heuberger J, et al. Comparing two imaging methods for follow-up of lung cancer treatment: A randomized pilot study. The Annals of Thoracic Surgery. 2019;**107**(2):430-435

[30] Nie K, Zhang YX, Nie W, Zhu L, Chen YN, Xiao YX, et al. Prognostic value of metabolic tumour volume and total lesion glycolysis measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography in small cell lung cancer: A systematic review and meta-analysis. Journal of Medical Imaging and Radiation Oncology. 2019;**63**(1):84-93

[31] Islam S, Walker RC. Advanced imaging (positron emission tomography

**76**

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[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018;**68**(6):394-424

**References**

cancer. Journal of Clinical Oncology.

[9] Howlader NNA, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, et al. SEER Cancer Statistics Review, 1975-2014. National Cancer Institute; 2017

[10] Carter BW, Glisson BS, Truong MT, Erasmus JJ. Small cell lung carcinoma: Staging, imaging, and treatment considerations. Radiographics.

[11] Brink I, Schumacher T, Mix M, Ruhland S, Stoelben E, Digel W, et al. Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer. European Journal of Nuclear Medicine and Molecular Imaging.

[12] Li C, Lu H. Adenosquamous

Therapy. 2018;**11**:4829-4835

carcinoma of the lung. OncoTargets and

[13] Noel-Savina E, Descourt R. Focus on treatment of lung carcinoid tumor. OncoTargets and Therapy.

[14] Jiang M, Anderson T, Nwogu C, Tan D. Pulmonary malignant granular cell tumor. World Journal of Surgical

[15] Roesel C, Terjung S, Weinreich G,

Metzenmacher M, et al. Sarcomatoid carcinoma of the lung: A rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages. Interactive Cardiovascular and Thoracic Surgery. 2017;**24**(3):407-413

2004;**22**(11):2184-2191

2014;**34**(6):1707-1721

2004;**31**(12):1614-1620

2013;**6**:1533-1537

Oncology. 2003;**1**(1):22

Hager T, Chalvatzoulis E,

[16] Li T, Kung HJ, Mack PC,

2013;**31**(8):1039-1049

Gandara DR. Genotyping and genomic profiling of non-small-cell lung cancer: Implications for current and future therapies. Journal of Clinical Oncology.

[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018;**68**(1):7-30

[3] Johnson DH, Schiller JH, Bunn PA Jr. Recent clinical advances in lung cancer management. Journal of Clinical

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Section 3

Medical Imaging Processing

Techniques

79

## Section 3
