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Distinguishing between macromolecular-driven magnetization transfer (MTSAT) and direct water saturation (MTDIR)
Dvir Radunsky1, Tamar Blumenfeld-Katzir1, and Noam Ben-Eliezer1,2,3
1Bio-medical Engineering, Tel Aviv University, Tel Aviv, Israel, 2Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel, 3Center for Advanced Imaging Innovation and Research (CAI2R), New-York University Langone Medical Center, New York, NY, United States

Synopsis

Mapping of T2 values is highly valuable for a wide range of applications. Still, accurate mapping is challenging due to the inherent bias of rapid Multi-Echo Spin-Echo (MESE) protocols by stimulated echoes, and also by magnetization transfer (MT). In this work, we investigate the different effects of macromolecular-driven MT (MTSAT) and direct water saturation (MTDIR) mechanisms on MESE signals, and their respective influence on T2 values. The investigation includes quantitative MT measurements between protocols with different scan settings and protocol schemes, aiming to isolate the individual roles of MTSAT and MTDIR.

Introduction

To date, Multi-Echo Spin-Echo (MESE) protocols constitute the most effective tool for quantifying T2 relaxation times in vivo. Nevertheless, the extensive use of radiofrequency (RF) pulses in MESE schemes leads to magnetization transfer (MT) related bias of the measured signal, and potential distortion of the measured T2 values1,2. Traditionally, MT ratio (MTR) measures the total relative signal loss between an MT-free protocol, e.g. Single-echo SE (SSE), and an RF intensive protocol, e.g. MESE, instigating MT effects. The measured MTR includes two distinct mechanisms: macromolecular-driven MT (MTSAT) and direct water saturation (MTDIR)3 and is calculated according to: $$$MTR=\frac{S_{MT-free}-S_{saturated}}{S_{MT-free}}$$$.
MTSAT refers to the transfer of magnetization between the saturated macromolecular pool (MMP) and the free water pool and can occur via cross-relaxation or chemical exchange phenomena4. MTDIR, on the other hand, refers to signal attenuation that originates from partial recovery of water protons between consecutive TRs, or from incidental irradiation of neighboring slices due to imperfect slice profile (i.e. slice crosstalk)5.
Previously we investigated the influence of MT on quantitative mapping of T2 values and showed that MT effect on MESE decay curve is constant and does not depend on scan settings. Still, MTSAT occurring within the imaged slice does distort the measured T2 values in comparison to SSE6. In this work we further explore the individual roles of MTSAT and MTDIR in MESE acquisitions, and quantify the effect of slice ordering on the measured signal and the ensuing T2 values. Since SSE and MESE signals are essentially different7,8, we analyze the evolution of MT along the respective echo trains, rather than echo-to-echo comparison.

Methods

Phantom preparation: six tubes were doped with 0.25 [mM] of MnCl2 and a unique urea concentrations of 0, 0.5, 1, 2, 3, and 4 Molars (Fig. 1). The urea molecule [CO(NH)2] is favorable for studying MT due to the high saturation efficiency of the amide groups9, and the spectral characteristics, which allows to design targeted experiments for probing MTDIR and MTSAT10.

MRI Scans were performed on a whole-body 3T Siemens Prisma scanner and included MRS analysis (STRESS), quantitative T1 (IR) and T2 (SSE and MESE) measurements, and estimation of MTR. Scan parameters for the T2-encoding protocols: TR/TE=3000/10 ms; Nechoes =1 (SSE), 10-30 (MESE), resolution=0.8x0.8 mm ; slice=4 mm; BW=200 Hz/Px ; Nslices =1-9; inter-slice gap= 0-200%; acceleration =2xGRAPPA;

Post-processing: Quantitative T2 maps were generated using mono-exponential fit to the SSE data, and using the Echo-Modulation-Curve (EMC) algorithm for the MESE data11–13.
MTSAT evaluation was based on the single-slice T2 dispersion between SSE and MESE protocols.
MTDIR was also estimated for MESE vs. SSE, and for different variants of MESE using varying ETL, TR, number of slices, inter-slice gap, and slice ordering schemes.

Results and Discussion

Fig. 2 shows the different effects of diffusion and MTSAT on SSE and MESE signals and T2 values. An expected decrease in baseline T2 is observed due to interactions with the urea molecules14. While SSE-T2 is lower at zero concentration due to diffusion effects, MTSAT dominates at higher concentrations, causing MESE-T2 values to be underestimated. Diffusion and MTSAT effects, which correspondly cause a positive and negative signal dispersion, shortens the measured T2 values and therefore depend on the pulse scheme and the MMP content (i.e. causing the MESE signal to be higher or lower).
The individual contribution of MTDIR in this case is presented in Fig. 3, where the 1st echo MTR was measured between single-slice SSE and MESE scans with different ETLs and TRs. Full transverse relaxation occurred between consecutive sequence repetitions (T2 << T1), thus the increased MTR baseline involves only MTDIR, which, in turn, depends on the T1/T2 ratio and the absolute T1 value of each tube15. Due to the shorter recovery time in short-TR experiments, the MTDIR increases with longer ETLs (*P<0.001). Consequently, MTDIR was not present for longer TRs. For any TR, the T2 values remained stable for increasing ETLs (not shown), indicating that MTSAT attenuation build up at a constant rate along the echo train.
Fig. 4 shows the effect of slice ordering in MESE scans. Sequential ordering yields higher MTDIR, compared to the interleaved mode, due to increased slice crosstalk effect (i.e. allowing minimal recovery time before scanning adjacent slices)5,16,17. The MTR increased with the number of slices in both ordering schemes, while increasing inter-slice gap exhibits an inverse correlation with MTR. This result indicates MTDIR changes, as the urea protons are excited in the boundaries of the central slice solely (i.e. confined spectral width), thereby off-resonance MTSAT is neglected. The T2 values (result not shown) are independent of the slice ordering, number of acquires slices or the gap between them, as MTDIR causes to a uniform signal attenuation, thereby not affecting the relative decay pattern6.

Conclusions

Herein we investigate the individual contribution of MTSAT and MTDIR to the signal and T2 bias in MESE protocols. This study is also relevant for Turbo-SE schemes, and can be generalized to any sequence where multiple RF pulses are applied in a series. More ex vivo and in vivo experiments will shed light on the effect and extent of MT mechanisms in quantitative MRI measurements, and will expand the understanding on the macromolecular regime.

Acknowledgements

ISF Grant 2009/17

References

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12. Ben-Eliezer N, Sodickson DK, Block TK. Rapid and Accurate T2 mapping from Multi Spin Echo Data Using Bloch-Simulation-Based Reconstruction. Magn Reson Med. 2015;73(2):809-817.

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Figures

Figure 1: T2 weighted image (TE=50 ms) of the urea phantom MT model. The inner circles mark the regions-of-interest (ROIs), where MTR and quantitative T2 values were estimated. Each ROI includes 115 pixels. Tubes number 1-6 are corresponding to urea concentrations of 0, 0.5, 1, 2, 3 and 4 Molars.

Figure 2: Signal and T2-relaxation bias due to diffusion and MT effects. (a) T2 values for SSE and MESE exhibit inverse correlation with urea concentration due to more restricted mobility and higher dipolar coupling between water molecules in the presence of macromolecules. (b) MTSAT development along the echo train - The MTR of the experimental MESE signal relatively to theoretical MT-free MESE signal (i.e. $$$ \frac{EMC_{MESE-T_2}}{EMC_{SSE-T_2}}*100\% $$$).

Figure 3: MTR (1st echo only) for different ETL and TR in a single-slice MESE. The MTR between the 1st echo of SSE and MESE was measured with a repetition time of (a) 3 sec, and (b) 10 sec. For shorter TR, where partial T1 recovery occurs, The MTR increases with longer ETLs (*P<0.001) due to residuals of MTDIR that cross the TR. The variation between the tubes sources from the individual T1/T2 ratio and the absolute T1 value of each, as they experience different amount of MTDIR.

Figure 4: Effect of interleaved and sequential slice ordering on MTR. MTR was calculated between single-slice and the middle of a multi-slice scan for (b) increasing number of slices (inter-slice gap=0%), and (c) increasing gap (Nslices=9). Dashed curves show the mean MTR±SD across all concentrations, for both ordering schemes. MTR increases with number of slices, and decreases for larger slice gap. Overall, sequential slice ordering yielded higher MTDIR due to increased slice crosstalk.

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)
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