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Purpose: To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases., Methods: The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T 1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T 2,f , T 2,b , R, and free pool T 1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T 1 ., Results: Bland-Altman analyses demonstrated a systematic underestimation of MPF (-2.5% and -1.3%, on average, in white and gray matter, respectively) and overestimation of T 1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (ΔMPF = -0.03% and ΔT 1  = -19.0 ms). The single-point methodology yielded consistent MPF and T 1 values with respective maximum relative average bias of -0.15% and -3.5 ms found in white matter., Conclusion: The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.) more...

Purpose: To identify T 1D -filtering methods, which can specifically isolate various ranges of T 1D components as they may be sensitive to different microstructural properties., Methods: Modified Bloch-Provotorov equations describing a bi-T 1D component biophysical model were used to simulate the inhomogeneous magnetization transfer (ihMT) signal from ihMTRAGE sequences at high RF power and low duty-cycle with different switching time values for the dual saturation experiment: Δt = 0.0, 0.8, 1.6, and 3.2 ms. Simulations were compared with experimental signals on the brain gray and white matter tissues of healthy mice at 7T., Results: The lengthening of Δt created ihMT high-pass T 1D -filters, which efficiently eliminated the signal from T 1D components shorter than 1 ms, while partially attenuating that of longer components (≥ 1 ms). Subtraction of ihMTR images obtained with Δt = 0.0 ms and Δt = 0.8 ms generated a new ihMT band-pass T 1D -filter isolating short-T 1D components in the 100-µs to 1-ms range. Simulated ihMTR values in central nervous system tissues were confirmed experimentally., Conclusion: Long- and short-T 1D components were successfully isolated with high RF power and low duty-cycle ihMT filters in the healthy mouse brain. Future studies should investigate the various T 1D -range microstructural correlations in in vivo tissues., (© 2022 International Society for Magnetic Resonance in Medicine.) more...

Purpose: To investigate the long- and short-T 1D components correlation with myelin content using inhomogeneous magnetization transfer (ihMT) high-pass and band-pass T ipt>1D -filters and to compare ihMT, R 1 , and the macromolecular proton fraction (MPF) for myelin specific imaging., Methods: The 3D ihMT rapid gradient echo (ihMTRAGE) sequences with increasing switching times (Δt) were used to derive ihMT high-pass T 1D -filters with increasing T 1D cutoff values and an ihMT band-pass T 1D -filter for components in the 100 µs to 1 ms range. 3D spoiled gradient echo quantitative MT (SPGR-qMT) protocols were used to derive R 1 and MPF maps. The specificity of R 1 , MPF, and ihMT T 1D -filters was evaluated by comparison with two histological reference techniques for myelin imaging., Results: The higher contribution of long-T 1D s as compared to the short components as Δt got longer led to an increase in the specificity to myelination. In contrast, focusing on the signal originating from a narrow range of short-T 1D s (< 1 ms) as isolated by the band-pass T 1D -filter led to lower specificity. In addition, the significantly lower r 2 correlation coefficient of the band-pass T 1D -filter suggests that the origin of short-T 1D components is mostly associated with non-myelin protons. Also, the important contribution of short-T 1D s to the estimated MPF, explains its low specificity to myelination as compared to the ihMT high-pass T 1D -filters., Conclusion: Long-T 1D components imaging by means of ihMT high-pass T 1D -filters is proposed as an MRI biomarker for myelin content. Future studies should enable the investigation of the sensitivity of ihMT T 1D -filters for demyelinating processes., (© 2022 International Society for Magnetic Resonance in Medicine.) more...

Purpose: 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-to-zero 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 ihMT imaging at 3 T. This feature is of particular interest for high and ultra-high field applications., (© 2021 International Society for Magnetic Resonance in Medicine.) more...

Inhomogeneous Magnetization Transfer (ihMT) is a development from the MT MRI technique. IhMT can be considered as a dipolar order relaxation time (T 1D ) weighted imaging modality whose signal has shown an enhanced selectivity for myelin-rich structures. However, a formal validation of the ihMT sensitivity relative to a gold standard myelin density measurement has not yet been reported. To address this need, we compared ihMT MRI with green fluorescence protein (GFP) microscopy, in a study performed on genetically-modified plp-GFP mice, considered as a reference technique for myelin-content assessment. Various ihMT protocols consisting of variable T 1D -filtering and radiofrequency power temporal distributions, were used for comparison with fluorescence microscopy. Strong and significant linear relationships (r 2 (0.87-0.96), p < 0.0001) were found between GFP and ihMT ratio signals across brain regions for all tested protocol variants. Conventional MT ratios showed weaker correlations (r 2 (0.24-0.78), p ≤ 0.02) and a much larger signal fraction unrelated to myelin, hence corresponding to a much lower specificity for myelin. T 1D -filtering reduced the ihMT signal fraction not attributed to myelin by almost twofold relative to zero filtering suggesting that at least half of the unrelated signal has a substantially shorter T 1D than myelin. Overall, these results strongly support the sensitivity of ihMT to myelin content., (Copyright © 2019 Elsevier Inc. All rights reserved.) more...

Purpose: Recently a new MR endogenous contrast mechanism was reported. It allows specifically imaging the magnetization transfer (MT) effect arising from inhomogeneously broadened components of the NMR spectrum, and was hence dubbed ihMT. Such unique NMR lineshape properties are presumably occurring in myelin because of its specifically ordered, multilayered sheath structure. Here, optimization of a pulsed ihMT preparation module is presented to provide guidance for future studies and improve the understanding of underlying contrast mechanisms., Methods: This study was performed at 1.5 Tesla on healthy volunteers. A pulsed ihMT preparation was implemented in combination with a HASTE readout module. The pulse width, interpulse repetition time, total saturation duration and RF saturation power were considered for optimization of the ihMT sensitivity and contrast., Results: An optimal configuration of the preparation module was derived, leading to 10% ihMT signal in internal capsule (relative to unsaturated data) and around 200% signal increase relative to gray matter, i.e., approximately 10-fold superior contrast compared with conventional MT ratios, measured under similar experimental conditions., Conclusion: Overall the ihMT sequence was robust, sensitive and very specific for white matter. These findings suggest great potential for assessing brain myelination and for better characterization of myelin related disorders., (© 2014 Wiley Periodicals, Inc.) more...