In this study, the whole brain qMT map from conventional MT imaging was compared with that from a newly proposed method, Segmented EPI readout Variable Flip angle Magnetization Transfer (EP-vfMT). The voxel-wise correlation shows a high correlation between the two maps. Compared to the conventional MT method, EP-vfMT provides similar image quality with good reproducibility. It also covers a whole brain volume in a much reduced scan time.
Introduction
In quantitative MT (qMT) imaging, signal from macromolecules is quantified using multiple sets of MT data1-4. Long scan times have impeded use of qMT among patients with neurological disease. Recently, Dortch et al. demonstrated whole-brain qMT imaging at 7T, however overall scan time is long for routine use in patients5.
Recently, a new qMT method, Segmented EPI readout Variable Flip angle Magnetization Transfer (EP-vfMT) has been proposed6. This method utilizes a 3D segmented EPI readout to cover a 3D volume rapidly and reduce EPI-associated artifacts. In order to reduce SAR while maintaining similar MT saturation to conventional MT, the flip angle of the MT RF pulse is varied as a function of the slice-encoding index. Compared to conventional methods, EP-vfMT acquires qMT data sets rapidly enough for clinical use. In this work, we compared a qMT map from EP-vfMT with results from a conventional method. The spatial distribution of the qMT map over the whole brain was compared qualitatively and quantitatively. Additionally, intra-session reproducibility was estimated using a test-retest scan.
Method
For the comparison of the whole brain qMT map, data were collected from an ex-vivo brain, 5 healthy controls and an in-situ multiple sclerosis (MS) postmortem brain (IRB approved) at 3T (Siemens Healthcare, Erlangen).
The EP-vfMT sequence diagrams are shown in Fig. 1. To cover a 3D volume rapidly and reduce EPI-associated artifacts, a 3D segmented EPI readout was utilized. In order to reduce SAR while maintaining similar MT saturation to conventional MT, the flip angle of the MT RF pulse was varied as a function of the slice-encoding index (Fig. 1(B)).
MR Scans: To demonstrate the spatial distribution of the qMT map from the EP-vfMT method, data were acquired with 10 different combinations of MT RF flip angles (212, 434, 843°) and offset frequencies (1000, 2500, 3500, 5000, 7500, 15000 Hz). The scan parameters are as follows: 1.6×1.6×4.0 mm3, NEX = 2, 200 dummy scans, TR = 32-40 ms (minimum TR depending on SAR limitations). The parallel imaging technique was not used. To generate the bound pool fraction map, the acquired data is fitted using a nonnegative least-squares fitting method proposed by Cabana et al.7
Parameter-matched conventional pulsed GRE-MT data were acquired. The scan parameters from EP-vfMT were used with the exception of TR, NEX and parallel imaging option, as follows: TR = 60-74 ms, NEX = 1, GRAPPA acceleration factor 3.
The bound pool fraction from qMT can be interpreted as a measure of myelin density. For comparison, alternative measures of myelin from ViSTa8-9 and multi-echo 3D GRASE10 were used for comparison.
Data analysis: After generating bound pool fraction maps from each method, a voxel-wise correlation was calculated in a brain mask, which was generated from the non-MT image segmented by FSL11.
Reproducibility: To test intra-session reproducibility, the EP-vfMT scan was acquired twice (7 day gap between 1st and 2nd scan) from a healthy control. An ex-vivo brain was scanned three times (on a different days) using conventional and EP-vfMT methods.
Result
EP-vfMT can achieve whole-brain coverage in a much shorter scan time (6.25 min with TR = 33ms) than the conventional method (26.2 min with TR = 62 ms).
Qualitative comparison of EP-vdMT against conventional qMT is shown in Fig. 2. Maps of bound pool fraction (F-maps) reveal similar signal distributions. In all maps, higher bound pool fraction is observed in regions with high myelin density (genu, splenium and internal capsule). When voxel-wise correlation was performed, the mean correlation coefficients were 0.95 ± 0.002 (ex-vivo brain, n = 3) and 0.81 ± 0.39 (healthy control, n = 5), suggesting a high similarity between the two maps.
A result of the reproducibility test result from a healthy control is shown in Fig. 3. Both F-maps reveal qualitatively similar signal distributions. Voxel-wise correlation was high (R = 0.96), and the slope of the trend line was 0.98, suggesting high similarity.
Figure 4 show images acquired in-situ from an MS patient within 6 hours of death. Demyelinated MS lesions demonstrated hypo-signal on the T1-weighted, ViSTa apparent myelin water fraction (aMWF) and 3D-GRASE based MWF images. The corresponding areas in the F-map demonstrated much reduced signal levels, clearly delineating T1-hypointense lesions (Fig. 4D).
Discussion and Conclusions
Compared to the conventional method, the proposed EP-vfMT provides a similar qMT map with whole brain coverage in a clinically feasible scan time. The EP-vfMT F-map shows a good correlation with the conventional method and demonstrates good reproducibility. Moreover, it maintains sensitivity to demyelinated T1-hypointense lesions. These features make the proposed method appealing for clinical neuroimaging applications.[1] Henkelman, R.M., Huang, X., Xiang, Q.S., Stanisz, G.J., Swanson, S.D., Bronskill, M.J., 1993. Quantitative interpretation of magnetization transfer. Magn Reson Med 29, 759-766.
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