The proposed sensitivity-boosted and time-efficient steady-state ihMT-gradient echo sequence, implemented and optimized at 1.5T, allowed robust high-resolution 3D ihMT imaging of the whole brain within a clinically compatible scan time. Magn Reson Med 79:2607-2619, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

• Inhomogeneous magnetization transfer (ihMT) was validated as a myelin sensitive imaging technique against fluorescence microscopy • ihMT signal was strongly and significantly correlated with myelin-related plp-GFP (proteolipid-Green Fluorescence Protein) signal • Short dipolar relaxation time (T1D) filtering is an efficient way to reduce non-myelin contribution in ihMT signal • MT signal was more weakly correlated with plp-GFP signal and had a much larger nonmyelin contribution • ihMT contrast can be varied with pulse timing, leading to different signal properties in terms of sensitivity and specificity for myelin content Data availability statement Data (Bruker format file) will be shared by request from any qualified investigator.

No abstract

A pulsed inhomogeneous magnetization transfer (ihMT)-prepared fast imaging sequence was implemented at 11.75 T for preclinical studies on mouse central nervous system. A strategy based on filtering the ihMT signal originating from short dipolar relaxation time (T ) components is proposed. It involves increasing the repetition time of consecutive radiofrequency (RF) pulses of the dual saturation and allows improved signal specificity for long T myelinated structures. Furthermore, frequency offset, power and timing saturation parameters were adjusted to optimize the ihMT sensitivity. The optimization of the ihMT sensitivity, whilst preserving the strong specificity for the long T component of myelinated tissues, allowed measurements of ihMT ratios on the order of 4-5% in white matter (WM), 2.5% in gray matter (GM) and 1-1.3% in muscle. This led to high relative ihMT contrasts between myelinated tissues and others (~3-4 between WM and muscle, and ≥2 between GM and muscle). Conversely, higher ihMT ratios (~6-7% in WM) could be obtained using minimal T filtering achieved with short saturation pulse repetition time or cosine-modulated pulses for the dual-frequency saturation. This study represents a first stage in the process of validating ihMT as a myelin biomarker by providing optimized ihMT preclinical sequences, directly transposable and applicable to other preclinical magnetic fields and scanners. Finally, ihMT ratios measured in various central nervous system areas are provided for future reference.

BACKGROUND AND PURPOSE:Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer.

T 1D , the relaxation time of dipolar order, is sensitive to slow motional processes. Thus T 1D is a probe for membrane dynamics and organization that could be used to characterize myelin, the lipid-rich membrane of axonal fibers. A mono-component T 1D model associated with a modified ihMT sequence was previously proposed for in vivo evaluation of T 1D with MRI. However, experiments have suggested that myelinated tissues exhibit multiple T 1D components probably due to a heterogeneous molecular mobility. A bi-component T 1D model is proposed and implemented. ihMT images of ex-vivo, fixed rat spinal cord were acquired with multiple frequency alternation rate. Fits to data yielded two T 1D s of about 500 µs and 10 ms. The proposed model seems to further explore the complexity of myelin organization compared to the previously reported mono-component T 1D model.

To minimize the sensitivity of inhomogeneous magnetization transfer gradient-echo (ihMT-GRE) imaging to radiofrequency (RF) transmit field (B + 1 ) inhomogeneities at 3 T. Methods:The ihMT-GRE sequence was optimized by varying the concentration of the RF saturation energy over time, obtained by increasing the saturation pulse power while extending the sequence repetition time (TR). Different protocols were tested using numerical simulations and human in vivo experiments in the brain white matter (WM) of healthy subjects at 3 T. The sensitivity of the ihMT ratio (ihMTR) to B + 1 variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global B + 1 drop. The resulting relative variations (δ ihMTR ) were evaluated voxelwise as a function of the local B + 1 distribution. The reproducibility of the protocol providing minimal B + 1 bias was assessed in a test-retest experiment. Results: In line with simulations, ihMT-GRE experiments conducted at high concentration of the RF energy over time demonstrated strong reduction of the B + 1 inhomogeneity effects in the human WM. Under the optimal conditions of 350-ms TR and 3-µT root mean square (RMS) saturation power, 73% of all WM voxels presented δ ihMTR below 10%. Reproducibility analysis yielded a close-tozero systematic bias (ΔihMTR = −0.081%) and a high correlation (ρ² = 0.977) between test and retest experiments. Conclusion:Concentrating RF saturation energy in ihMT-GRE sequences mitigates the sensitivity of the ihMTR to B + 1 variations and allows for clinical-ready