shows a commonly used fast SE-CEST MRI method along with the proposed RF irradiation-segmented GE CEST MRI pulse sequence. The conventional sequence includes three periods: relaxation recovery, RF irradiation, and fast image acquisition (). It is important to note that the RF irradiation can be either continuous wave (CW) or RF pulse train (17
). Using fast image acquisition, one can obtain multi-slice images after a single long RF irradiation, and the relaxation-induced loss of contrast can be corrected during post-processing (24
). In comparison, the proposed sequence utilizes the long primary RF irradiation module to generate the steady state CEST contrast, and short secondary RF pulses applied immediately after each slice acquisition to maintain the steady state CEST contrast (). As such, whereas magnetization recovers towards the equilibrium state during image readout, following the intrinsic longitudinal relaxation rate of bulk water (R1w
), the secondary RF irradiation module re-saturates the magnetization towards the steady state CEST contrast at a rate governed by the apparent longitudinal relaxation rate of bulk water (r1w
). Because multi-slice acquisition and signal averaging are conducted with the short secondary saturation pulse rather than with the long primary RF irradiation, its total scan time can be shown to be t = Tr + TS1
+ NA * NS * TS2
, where Tr is the pre-saturation delay, NA and NS being the number of averages and number of slices, with TS1
being the primary and secondary RF saturation duration. In comparison, the total scan time for the conventional CEST MRI is equal to NA * (Tr + TS1
). In addition, if the maximal pulse duration is limited by RF amplifier, the proposed sequence can be divided into multiple sets of averages. The total scan time will become t = NA2
* (Tr + TS1
* NS * TS2
) and NA=NA1
compares multi-slice CEST Z-spectra and MTRasym obtained with both the conventional and proposed modified sequences. Specifically, shows Z-spectra of the inner pH compartment, as acquired using the conventional multi-slice CEST (B1=1.5μT). It is clear that longitudinal relaxation induced noticeable signal recovery (loss of contrast). Specifically, whereas the signal intensity at water resonance was 1% during acquisition of the first slice, it relaxed to about 11% when the final slice was acquired. The MTRasym was found to be 10.8 ± 0.4% (mean ± SD) at 1.9 ppm from water resonance (). In comparison, Z-spectra obtained using the proposed sequence nearly overlapped for all 5 slices (TS2=1 s, ). In addition, the MTRasym () appeared more symmetrical around the labile proton frequency. The results confirmed that although the duration of multi-slice image acquisition is relatively short, there is still significant change in the MR signal, which can be effectively compensated by the secondary RF saturation pulse. Using the modified sequence, the total acquisition time for the Z-spectrum was about 20, 18, 16, 14 and 12 min for TS2 times of 2.5, 2, 1.5, 1 and 0.5 s, respectively, equal to or shorter than the conventional sequence (~20 min). The CEST contrast at 1.9 ppm was found to be 11.3 ± 0.4%, slightly above that obtained with the conventional method. The fact that the modified CEST sequence showed large improvement in Z-spectra while only subtle change in MTRasym was observed is likely due to the short image acquisition time (~60 ms per slice) relative to T1. Indeed, T1 was found to be 2.59 ± 0.03 s and 2.54 ± 0.03 s, respectively, for the inner (pH=6.7) and outer (pH=5.7) compartments, while the respective T2 of these compartments were 68 ± 8 ms and 73 ± 5 ms. Nevertheless, the significant improvement in Z-spectra and the reduction of the total scan time suggested that the modified fast multi-slice RF-segmented CEST sequence, if optimized, may indeed augment CEST MRI.
Fig. 2 Comparison of CEST MRI obtained with the conventional and modified sequences. Z-spectra and MTRasym were obtained with the conventional CEST MRI (a and b) and those obtained using the proposed RF-segmented GE CEST MRI sequence (c and d). Whereas relaxation (more ...)
shows the obtained CEST contrast as a function of the secondary RF irradiation time (TS2
). Specifically, the CEST contrast for the inner pH compartment was higher than that of the outer compartment, which is consistent with the fact that amine proton exchange is dominantly base-catalyzed (5
). For the B1
amplitude of 0.75 μT, the CEST contrast was found to be 10.9%+0.3%*TS2
, and 6.2%-0.04%*TS2
for pH of 6.7 and 5.7, respectively (). A similar relationship was found for B1
of 1.5 μT, where CEST was measured at 11%+0.7%*TS2
(). Linear regression analysis (ANOVA) showed that the dependence of CEST contrast over TS2
is insignificant (F>0.05). Hence, the CEST contrast obtained from the modified fast sequence is comparable to that obtained using the conventional method, and with significantly reduced scan time.
Fig. 3 Dependence of CEST contrast (mean ± S.D.) as a function of TS2. CEST contrast obtained with conventional sequence was shown in gray. The CEST contrast showed very little change with TS2 for both pH compartments, suggesting that the short secondary (more ...)
Given that a secondary RF irradiation pulse as short as 0.5 s may be sufficient to maintain CEST contrast for multi-slice acquisition (), the effective repetition time may be significantly reduced from that of the conventional CEST MRI method. Hence, to take the advantage of fast repetition time, we postulate that the GE sequence should be used, and that its excitation angle must be optimized. We repeated CEST imaging by systematically varying the RF flip angle, from 15° to 90° in six steps. shows multi-slice MTRasym maps obtained with the conventional sequence and the modified sequence. The CEST contrast appeared to be maximal at 15°, while its contrast-to-noise ratio (CNR) seemed to be very poor, suggesting that the imaging flip angle must be optimized such that both large CEST contrast and high CNR could be simultaneously obtained. Indeed, shows that the CEST contrast was maximal at 15°, decreasing slightly with flip angle for both compartments. This change may be attributed to the fact that large flip angle significantly perturbs the CEST steady state, which may not fully recover under a short secondary RF irradiation, as used here (TS2= 0.5 s). In comparison, the CEST CNR initially increased with flip angle, peaking at around 60°, and then decreased for larger flip angles (i.e., 75° and 90°, ). It is important to note that the CEST MRI CNR reflects not only the CEST contrast, but also the signal-to-noise ratio (SNR) of the image. Therefore, whereas a small flip angle minimally perturbs the spin state, leading to maximal CEST contrast, image intensity is low, and hence, suffers from poor SNR. In sum, we showed that for the gel CEST phantom undergoing slow and intermediate chemical exchange, comparable CEST contrast can be obtained with either sequence, while the modified sequence significantly improved the CNR over the conventional CEST MRI sequence.
Fig. 4 Evaluation of the CEST MRI contrast as a function of the GE excitation angle. a) Multi-slice MTRasym map (±1.9 ppm) obtained using the conventional SE CEST MRI and the modified fast GE CEST MRI with the excitation angle varied from 15°, (more ...)
shows apparent diffusion coefficient (ADC) and APT maps of a representative stroke animal, about 1 hr after MCAO. The stroke lesion appeared as hypointensity in the ADC map, which also showed reduction in MTRasym
maps, both the conventional and modified APT MRI. Two regions of interest (ROI) were selected in the ADC map, one in the contralateral area (cROI) and another one in the ipsilateral stroke lesion (iROI). Their ADCs were 0.73 ± 0.05 μm2
/ms and 0.59 ± 0.06 μm2
/ms, respectively. For the conventional APT MRI, the MTRasym
for cROI and iROI was −1.5% ± 0.8% and −3.3% ± 0.8% and, while being −1.4% ± 0.7% and −2.9% ± 0.6% for the proposed method, respectively. It is important to whereas long CW RF irradiation is used, its average SAR for the head was estimated to be about 0.7 W/kg, assuming 100% RF duty cycle, for an RF amplitude of 0.75 μT (27
). This shows that for weak RF power used in our study, the energy deposition is well within the SAR limit, feasible for in vivo applications and clinical translation.
Fig. 5 Diffusion and pH-weighted endogenous APT MRI of a representative acute stroke animal. a) Ischemic lesion appeared as hypointensity in the ADC map. Two ROIs were manually drawn in a representative slice for lesion analysis. b) pH-weighted APT MRI with (more ...)