**2.3. Positron emission tomography**

**4.** Dynamic acquisition as a function of time: a number of successive static images used to reconstruct a video to study some interesting dynamic biological processes. Interesting applications are: kidney and bone phase's vascular scans and scintigraphy of the heart

10 Imaging and Radioanalytical Techniques in Interdisciplinary Research - Fundamentals and Cutting Edge Applications

This medical imaging method was introduced in 1963 by Kuhl and Edwards [10]. Known by the acronym SPECT (Single Photon Emission Computerized Tomography), this imaging method is equivalent in scintigraphy to Computed Tomography (CT) in radiology. The injected radioactive tracers emit during their disintegration gamma photons which are detected by an external detector, after passing through the surrounding tissue. Because the gamma photons emission is isotropic, a collimator is placed before the detector to select the direction of the photons to be detected. Thus, if we call f(x, y, z) the distribution of radioactivity emitted point {x, y, z} per unit solid angle, the number of photons detected at the point {x',y'}

Where L is the line given by the direction of the channel's collimator and passing through the point (x',y'). As in CT, the various projections are obtained by rotating the detector around the

**<sup>y</sup>**(x',y')

L

acquisition synchronized by the heartbeat which is recorded by ECG.

¢ ¢ <sup>=</sup> ò L

f(x,y,z)

Object

**2.2. Single photon emission computed tomography**

of the detector is equal to (Figure 6) [11]:

**Figure 6.** Detection principle in SPECT imaging.

1 ECG : Electrocardiogram.

 gated acquisition: used for tomographic myocardial scintigraphy. In this applica‐ tion, detectors are arranged in the shape of an "L» and simultaneously record the radio‐ activity from the myocardium and the electrical activity of the heart. Thus it is a dynamic

N(x , y ) f(x, y,z)ds (1)

**x** 

**s** 

Collimator

ventricle.

object (patient).

**5.** ECG1

Positron emission tomography (PET) is a medical imaging modality that measures the threedimensional distribution of a molecule labelled with a positron emitter. The acquisition is carried out by a set of detectors arranged around the patient. The detectors consist of a scintillator which is selected according to many properties, to improve the efficiency and the signal on noise. The coincidence circuit measures the two 511 keV gamma photons emitted in opposite directions resulting from the annihilation of the positron. The sections were recon‐ structed by algorithms, the same but more complex than those used for conventional CT, to accommodate the three-dimensional acquisition geometries. Correction by considering the physical phenomena provides an image representative of the distribution of the tracer. In PET scan an effective dose of the order of 8 mSv is delivered to the patient. This technique is in permanent evolution, both from the point of view of the detector and that of the used image reconstruction algorithms. A new generation of hybrid scanner "PET-CT" provides additional information for correcting the attenuation, localize lesions and to optimize therapeutic procedures. All these developments make one PET fully operational tool that has its place in medical imaging.

**•** Toxicology (carcinogen and mutagenic substances).

**2.4. PET and SPECT images processing and analysis**

The realization of a PET scan is the result of a set of operations, since the production of the isotope, the synthesis of the molecule, the injection of the radioactive tracer, the detection of radiation, the tomographic reconstruction, and finally the application of a series of corrections

**Isotopes 11C 15N 15O 18F 76Br**

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Period (mn) 20.4 10.0 2.1 109.8 972

Maximum kinetic energy of β+ (MeV) 0.98 1.19 1.72 0.63 3.98

Maximum Free path in water (mm) 3,9 5 7,9 2,3 20

**Table 1.** Physical characteristics of the main isotopes positron emitters used in positron emission tomography (PET).

The principle of PET is based coincidence 511 keV Gamma-photons detection (created by positron annihilation) by considering the parallelepiped joining any two detector elements as a volume of response (Figure 8, a). In the absence of physical effects such as attenuation, scattered and accidental coincidences, detector efficiency variations, or count-rate dependent effects, the total number of coincidence events detected will be proportional to the total amount of tracer contained in the tube or volume of response. Both Two and three dimensional modalities are available for one scan and it depends on the collimator-Detector system used. In two dimensional PET imaging, only lines of response lying within a specified imaging plane are considered (Figure 8, b). The lines of response are then organized into sets of projections. The collection of all projections obtained by rotation around the patient forms a two dimen‐ sional function called a sonogram which will be used for 2D image reconstruction. Multiple 2-D planes are can be stacked to form a 3-D volume. In fully three-dimensional PET imaging, the acquisition is performed both in the direct planes as well as the line-integral data lying on 'oblique' imaging planes that cross the direct planes, as shown in figure 8 c. PET scanners operating in fully 3-D mode increase sensitivity, and thus reduce the statistical noise associated with photon counting and improve the signal-to-noise ratio in the reconstructed image.

Tomographic slices are reconstructed from the acquired projection data using either analytic or iterative algorithms. Analytic reconstructions represent an exact mathematic solution, and there is a general solution for true projection data: filtered backprojection. Although filtered backprojection is a relatively efficient operation, it does not always perform well on noisy projections and, as is the case with SPECT and PET data, it generates artifacts when the projections are not line integrals of the internal activity. Iterative algorithms are a preferred alternate method for performing SPECT reconstruction, and over the past 10 years there has been a shift from filtered backprojection to iterative reconstruction in most clinics [23-26]. The

to provide image representative of the distribution of the tracer within the patient.

The main physical characteristics of isotopes used in PET are summarized in Table 1.

**Figure 7.** Different kinds of collimators used with SPECT imaging system (O: object, I: image).

Positron emitters are radioactive isotopes (11C, 13N, 15O, 18F) which can easily be incorporated molecules without altering their biological properties [15-22]. The first 18F labelled molecules were synthesized to late 1970s. At the same time, were built the first emission tomography scanners (PET cameras) used in a clinical setting. Since the 1970, many studies conducted by research centres and industrialists have allowed the development of PET to perform tests whole body, in conditions of resolution and adapted sensitivity. Until the last decade, PET was available only in centres equipped with a cyclotron capable of producing the different isotopes. However, today's growing role PET in oncology is reflected in the rapid spread of this medical imaging modality in hospitals. The operation of these structures is based on the installation of PET machine, and the implementation a network distribution radio-pharmaceutical marked by 18F, characterized by a half life of 110 minutes. The most widely used molecule is the Fluorodeoxyglucose (FDG) labelled with fluorine 18 (18F-FDG) due to its many properties and advantages. Generally to find the right tracer molecule, a close look into the designated processes and the related biochemistry is necessary, the following gives a short overview:


**•** Toxicology (carcinogen and mutagenic substances).

The realization of a PET scan is the result of a set of operations, since the production of the isotope, the synthesis of the molecule, the injection of the radioactive tracer, the detection of radiation, the tomographic reconstruction, and finally the application of a series of corrections to provide image representative of the distribution of the tracer within the patient.

The main physical characteristics of isotopes used in PET are summarized in Table 1.


**Table 1.** Physical characteristics of the main isotopes positron emitters used in positron emission tomography (PET).

The principle of PET is based coincidence 511 keV Gamma-photons detection (created by positron annihilation) by considering the parallelepiped joining any two detector elements as a volume of response (Figure 8, a). In the absence of physical effects such as attenuation, scattered and accidental coincidences, detector efficiency variations, or count-rate dependent effects, the total number of coincidence events detected will be proportional to the total amount of tracer contained in the tube or volume of response. Both Two and three dimensional modalities are available for one scan and it depends on the collimator-Detector system used. In two dimensional PET imaging, only lines of response lying within a specified imaging plane are considered (Figure 8, b). The lines of response are then organized into sets of projections. The collection of all projections obtained by rotation around the patient forms a two dimen‐ sional function called a sonogram which will be used for 2D image reconstruction. Multiple 2-D planes are can be stacked to form a 3-D volume. In fully three-dimensional PET imaging, the acquisition is performed both in the direct planes as well as the line-integral data lying on 'oblique' imaging planes that cross the direct planes, as shown in figure 8 c. PET scanners operating in fully 3-D mode increase sensitivity, and thus reduce the statistical noise associated with photon counting and improve the signal-to-noise ratio in the reconstructed image.

### **2.4. PET and SPECT images processing and analysis**

Positron emitters are radioactive isotopes (11C, 13N, 15O, 18F) which can easily be incorporated molecules without altering their biological properties [15-22]. The first 18F labelled molecules were synthesized to late 1970s. At the same time, were built the first emission tomography scanners (PET cameras) used in a clinical setting. Since the 1970, many studies conducted by research centres and industrialists have allowed the development of PET to perform tests whole body, in conditions of resolution and adapted sensitivity. Until the last decade, PET was available only in centres equipped with a cyclotron capable of producing the different isotopes. However, today's growing role PET in oncology is reflected in the rapid spread of this medical imaging modality in hospitals. The operation of these structures is based on the installation of PET machine, and the implementation a network distribution radio-pharmaceutical marked by 18F, characterized by a half life of 110 minutes. The most widely used molecule is the Fluorodeoxyglucose (FDG) labelled with fluorine 18 (18F-FDG) due to its many properties and advantages. Generally to find the right tracer molecule, a close look into the designated processes and the related biochemistry is necessary, the following gives a short overview:

12 Imaging and Radioanalytical Techniques in Interdisciplinary Research - Fundamentals and Cutting Edge Applications

**Figure 7.** Different kinds of collimators used with SPECT imaging system (O: object, I: image).

**•** Metabolism and general biochemical function;

**•** Receptor-ligand biochemistry;

**•** Enzyme function and inhibition;

**•** Immune reaction and response;

**•** Pharmaceutical effects.

Tomographic slices are reconstructed from the acquired projection data using either analytic or iterative algorithms. Analytic reconstructions represent an exact mathematic solution, and there is a general solution for true projection data: filtered backprojection. Although filtered backprojection is a relatively efficient operation, it does not always perform well on noisy projections and, as is the case with SPECT and PET data, it generates artifacts when the projections are not line integrals of the internal activity. Iterative algorithms are a preferred alternate method for performing SPECT reconstruction, and over the past 10 years there has been a shift from filtered backprojection to iterative reconstruction in most clinics [23-26]. The

**7.** Segmentation: process of partitioning a digital image into multiple segments to simplify and/or change the representation of an image into something that is more meaningful and

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In addition to these pre-processing methods which have an impact on the interpretation of the results, there are other processing methods that must be applied to SPECT image to extract essential information according to the studied pathologic case. Thus, SPECT images can be processed by various methods such as: 1) "Principal Components Analysis (PCA) which is a multivariate analysis method that aims at revealing the trends in the data by representing the data in a dimensionally lower space[27], 2) "Discrimination Analysis (DA)" used to identify a discrimination vector such that projecting each data set onto this vector provides the best possible separation between population groups subject to SPECT study and 3) Bootstrap Resampling which is applied to evaluate the robustness and the predictive accuracy of the

**3. Recent development in nuclear imaging and image analysis**

The key technology in the development of SPECT and PET systems for static or dynamic image acquisition is embodied in the development of the detector, or rather, the detector chain. Although it has already reached a high degree of perfection, continuous improvements are still increasing the performance of, for example, the scintillator material, which is a critical component in the chain. The time of flight camera, introduced by Philips Medical Systems in the 1980s, is replacing the conventional Anger camera and offers significant improvements in image quality. The trend here is towards higher resolution where, for certain applications, 2048 x 2048 pixel matrices will be used. In addition to continuous improvements in the detector chain, there are also radically novel approaches which dispense with the need for a semicon‐ ductor detector. A detector based on scintillator crystals coupled to hybrid photodetectors that provides full 3D reconstruction in PET imaging with high resolution and avoiding parallax

Another improvement is SPECT systems provision on a single stand of rotation of several (two or three) detecting heads, allowing examination time reduction and detection sensitivity increasing. In addition, one of the heads can record a transmission coefficient image induced by a radioactive external gamma source photons of the same energy as those issued by the tracer during the examination. These acquisitions are then used to correct the effect of self-

Development of SPECT and PET systems much more efficient enable major advances in the clinical use of these techniques with very widespread applications field. Additional develop‐ ment may include research on more efficient scintillators, the use of more adequate recording

**3.1. Recent advances in SPECT and PET imaging systems**

errors developed during last ten years are actually available [29, 30].

easier to analyze;

PCA and DA approach [28].

absorption.

**8.** Volume fraction calculation.

**Figure 8.** Principle of PET imaging and 2D and full 3D image acquisition modes.

big advantage of the iterative approach is that accurate corrections can be made for all physical properties of the imaging system and the transport of γ-rays that can be mathematically modeled. This includes attenuation, scatter, septal penetration in the case of SPECT, and spatial resolution. In addition, streak artifacts common to filtered backprojection are largely elimi‐ nated with iterative algorithms. A major advance was the introduction of the ordered-subset expectation maximization approach, which produces usable results with a small number of iterations.

In each study, the PET or SPECT images selected for statistical analysis are registered, smoothed and intensity normalized and this because of the following objectives:


Key PET and SPECT image processing parameters include also the following:


big advantage of the iterative approach is that accurate corrections can be made for all physical properties of the imaging system and the transport of γ-rays that can be mathematically modeled. This includes attenuation, scatter, septal penetration in the case of SPECT, and spatial resolution. In addition, streak artifacts common to filtered backprojection are largely elimi‐ nated with iterative algorithms. A major advance was the introduction of the ordered-subset expectation maximization approach, which produces usable results with a small number of

14 Imaging and Radioanalytical Techniques in Interdisciplinary Research - Fundamentals and Cutting Edge Applications

**(a) (b) (c)** 

Detectors

Coïncidence lines

In each study, the PET or SPECT images selected for statistical analysis are registered,

**•** Registration is required to align the data sets, which is an important step for any kind of

**•** Smoothing effectively reduces differences in the data, which cannot be compensated for by registration alone, such as intrapatient variations in pathology, and the resolution of the

**•** Intensity values of the data sets may vary significantly, depending on the individual physiology of the patient (e.g., injected dose, body mass, washout rate, metabolic rate). These factors are not relevant in the study of the disease, and need to be eliminated using intensity normalization, to obtain meaningful statistical comparisons during multivariate analysis.

reconstruction of scans. Another reason for smoothing is the reduction of noise.

Key PET and SPECT image processing parameters include also the following:

**3.** Motion correction: recommended to reduce motion blur due to object motion; **4.** Attenuation correction: identifying source of attenuation for image correction;

**6.** Normal database: reference used for calculation of extent and severity of defect;

**5.** Quantification: assessment by image quantification of the affected area;

**1.** Filtering: improve image quality by removing noise and blur;

**2.** Reconstruction: by analytical or iterative methods;

smoothed and intensity normalized and this because of the following objectives:

iterations.

voxel-by-voxel-based image analysis.

Coïncidence lines Detectors corona

**Figure 8.** Principle of PET imaging and 2D and full 3D image acquisition modes.

In addition to these pre-processing methods which have an impact on the interpretation of the results, there are other processing methods that must be applied to SPECT image to extract essential information according to the studied pathologic case. Thus, SPECT images can be processed by various methods such as: 1) "Principal Components Analysis (PCA) which is a multivariate analysis method that aims at revealing the trends in the data by representing the data in a dimensionally lower space[27], 2) "Discrimination Analysis (DA)" used to identify a discrimination vector such that projecting each data set onto this vector provides the best possible separation between population groups subject to SPECT study and 3) Bootstrap Resampling which is applied to evaluate the robustness and the predictive accuracy of the PCA and DA approach [28].
