**3.2 TrueFISP**

The specificity of bSSFP (balanced Steady-State Free Precession) type sequences, also known as TrueFISP or FIESTA, is their perfect symmetry, with an echo time (TE) equal to half the repetition time (TR). This maintains the magnetization in the transverse plane. Due to spin dephasing, the signal generated is more intense than with gradient-echo sequences. This allows 3D images to be constructed with good spatial resolution within a reasonable acquisition time. Besides, the tissue contrast generated is proportional to the T1/T2 ratio. The alternating phase RF pulse method must be used with 4 or 8 Δφ phase values (180°, 0°, 90°, 270°; 45°, 135°, 225°, 315°). Image reconstruction is based on the Sum-Of-Square (SOS) method, i.e. calculation of the square root of the sum of squares of the magnitude signal.

Fig. 4. 3D TrueFISP sequence chronogram. The RF pulse phase indicated generates images corresponding to the following Δφ values: 180°, 0°, 90°, 270°. The sequence is perfectly symmetrical about the center of the echo. Thus, the echo time (TE) is equal to half the repetition time (TR).

The following sequence parameters are used:


#### **3.3 Theory**

130 Advances in the Biology, Imaging and Therapies for Glioblastoma

T2-weighted sequences are the most widely used for imaging-based tumor detection. These are accelerated spin-echo sequences (RARE, or Rapid Acquisition with Refocused Echoes) which are generally acquired in two dimensions (2D), in multi-slice mode. When these sequences are used for clinical imaging, pulses are often added to suppress fluid signals

TE/TR = 70/5,000 ms; FOV: 22.5 x 22.5 mm; matrix: 192 x 128; spatial resolution: 117 x 175 µm; slice thickness: 750 µm; excitation pulse: Hermite 1 ms, 90°; refocusing pulse: Hermite 1 ms, 180°; reception bandwidth: 260 Hertz/pixel; RARE factor: 32; number of

The specificity of bSSFP (balanced Steady-State Free Precession) type sequences, also known as TrueFISP or FIESTA, is their perfect symmetry, with an echo time (TE) equal to half the repetition time (TR). This maintains the magnetization in the transverse plane. Due to spin dephasing, the signal generated is more intense than with gradient-echo sequences. This allows 3D images to be constructed with good spatial resolution within a reasonable acquisition time. Besides, the tissue contrast generated is proportional to the T1/T2 ratio. The alternating phase RF pulse method must be used with 4 or 8 Δφ phase values (180°, 0°, 90°, 270°; 45°, 135°, 225°, 315°). Image reconstruction is based on the Sum-Of-Square (SOS) method, i.e. calculation of the square root of the sum of squares of the magnitude signal.

Fig. 4. 3D TrueFISP sequence chronogram. The RF pulse phase indicated generates images corresponding to the following Δφ values: 180°, 0°, 90°, 270°. The sequence is perfectly symmetrical about the center of the echo. Thus, the echo time (TE) is equal to half the

**3. Sequence 3.1 RARE 2D** 

in 2D

**3.2 TrueFISP** 

repetition time (TR).

(FLAIR, or Fluid-Attenuated Inversion Recovery).

To image small animals, the following parameters are used:

averages: 32, total acquisition time: 10 min 40 sec; transverse orientation.

Simulations of the state of magnetization with TrueFISP, gradient-echo and spin-echo sequences were performed in Igor Pro using well-known equations (Eq. [4], [5] and [6)]. They were performed as a function of flip angle α, TR, TE or the T1 and T2 values of tissues. At 4.7 T, the T1 and T2 values of brain was equal to 1,295 ms and 53 ms, respectively, and for tumors, 1,525 and 72 ms, respectively [8].


$$S\_{\text{TrozPIS}} = \frac{\text{(1 - \exp^{\text{TR/Tl}}) \sin a}}{\text{1 - (\exp^{\text{TR/Tl}} - \exp^{\text{TR/Tl}}) \cos a - (\exp^{\text{TR/Tl}} \exp^{\text{TR/Tl}})} \tag{4}$$


$$\mathbf{S}\_{\text{GE}} = \frac{\langle \mathbf{1} \text{ - } \mathbf{e} \mathbf{x} \mathbf{p}^{\text{-} \text{TR/T1}} \rangle \sin \alpha}{\mathbf{1} \text{ -} \cos \alpha \text{ (exp} \mathbf{p}^{\text{-} \text{TR/T1}} \text{)}} \, \text{ } \mathbf{e} \mathbf{x} \mathbf{p}^{\text{-} \text{TR/T2}} \, \text{ } \tag{5}$$

with TE = 2.5 ms and T2\* = 25 ms


A 1/6.32 correction factor was applied to 2D RARE (Eq. [6]), corresponding to the voxel size, the number of averages and the number of k-space samples by comparison with 3D TrueFISP acquisition.

$$\mathbf{S}\_{\rm SE} = \left(1 \cdot 2 \exp^{\rm{TE/2-TR/IT}}\right) + \exp^{-\rm{TR/IT}}\right) \cdot \exp^{\rm{TE/TE/}}\tag{6}$$

S/N was simulated for the brain and tumor, and contrast was evaluated according to Eq. [7].

$$\mathbf{\color{red}{Contrast}} = \mathbf{S\_{Tuncor} - \mathbf{S\_{Brain}}} \tag{7}$$

The signal-to-noise ratio was evaluated for both tumor and brain tissues. For the TrueFISP sequence, the maximal signal was obtained with the shortest possible TE and a flip angle between approximately 15° and 35°, as shown in Figs. 5ab. The slight S/N difference between the healthy brain and the tumor is also observable. The gradient-echo sequence generates a much lower S/N compared with the TrueFISP sequence for all flip angles.

3D TrueFISP MRI Provides Accurate Longitudinal Measurements of Glioma Volumes in Mice 133

To conclude on these simulations (S/N and contrast), a very high S/N can be expected with the TrueFISP sequence. This method provides adequate contrast between the brain and tumor with flip angles around 30° and short TEs. Yet, contrast should be improved with the T2-weighted accelerated spin-echo sequence (RARE), but this method is generally used to acquire 2D images only, thus limiting its capacity to measure tumor volumes. Using it for 3D imaging can produce artifacts due to movements, and the acquisition time is much

Fig. 6. Simulation of the contrast between tumor and brain using a) the 3D TrueFISP sequence, b) the 3D gradient-echo sequence, and c) the 2D spin-echo sequence. The contrast is estimated as a function of the flip angle and TR for the TrueFISP and gradient-echo

TrueFISP images were acquired at 4.7 T using a cross-polarized antenna. A U87 glioma was

Fig. 7.a shows the image acquired using the TrueFISP sequence with a TE of 2.5 ms, a flip angle of 35°, and a Δφ value of 180°. As expected, black-signal bands are clearly visible in the image. These hinder visualization of parts of the animal's brain. Modifying the Δφ value (to 0°, 90°, and 270°) shifts the positions of the null-signal bands. For some of these values (Δφ = 270°), the tumor is clearly visible, while for others (Δφ = 90°), the null-signal zone covers the area containing the tumor, making all subsequent analyses of the tumor

sequences, and as a function of TE and TR for the spin-echo sequence.

implanted in a mouse, and imaging was performed 4 days later.

**4.1 Correction of TrueFISP banding artifacts** 

**4. Results** 

impossible.

longer than with the TrueFISP sequence.

Fig. 5. Modeling of the signal-to-noise ratio using the above equations for: ab) the TrueFISP sequence, c) the gradient-echo sequence, and d) the spin-echo sequence. The signal was estimated as a function of the flip angle and TR for a), b), and c). For the spin-echo sequence, the signal was estimated as a function of the TEs and TRs of the sequence. The T1 and T2 values for the brain (1,295 ms and 53 ms, respectively) were used in a), c), and d). The T1 and T2 values for the tumor (1,525 ms and 72 ms, respectively) were used in b). The same color scale was used in the 4 simulations. To allow for the 2-dimensional nature of the spinecho sequence, a correction factor was applied.

The spin-echo sequence should provide a high S/N, provided the TR is long and TE very short. However, these acquisition conditions do not provide sufficient contrast, as shown in the following figure.

We can thus clearly see the advantage of the TrueFISP sequence, as far as the S/N is concerned, for an equivalent total acquisition time, compared with both a standard 3D gradient-echo sequence and a 2D RARE spin-echo sequence.

#### **3.4 Contrast**

The contrast was then assessed theoretically, based on the signal difference between the tumor and the healthy brain. For the TrueFISP sequence (Fig. 6a), optimal contrast was achieved with a short TE and a flip angle between 25° and 50°.

The gradient-echo sequence provided almost no contrast compared with the TrueFISP sequence, while the spin-echo sequence provided improved contrast for TRs over 3,500 ms and TEs greater than 50 ms.

To conclude on these simulations (S/N and contrast), a very high S/N can be expected with the TrueFISP sequence. This method provides adequate contrast between the brain and tumor with flip angles around 30° and short TEs. Yet, contrast should be improved with the T2-weighted accelerated spin-echo sequence (RARE), but this method is generally used to acquire 2D images only, thus limiting its capacity to measure tumor volumes. Using it for 3D imaging can produce artifacts due to movements, and the acquisition time is much longer than with the TrueFISP sequence.

Fig. 6. Simulation of the contrast between tumor and brain using a) the 3D TrueFISP sequence, b) the 3D gradient-echo sequence, and c) the 2D spin-echo sequence. The contrast is estimated as a function of the flip angle and TR for the TrueFISP and gradient-echo sequences, and as a function of TE and TR for the spin-echo sequence.
