Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time (T_1D) filtering

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.

A multiparametric analysis of white matter maturation during late childhood and adolescence

“…QihMT is correlated with VF m (Geeraert et al, ), but these measures assess myelin through different methods. The mcDESPOT model estimates the fraction of water bound within the myelin sheath based on the unique T1 and T2 characteristics of water in that environment (Deoni et al, ), while ihMT provides contrast based upon dipolar coupling in lipid bilayers, and is primarily driven by myelin in white matter tissue (Manning, Chang, MacKay, & Michal, ; Prevost et al, ; Swanson et al, ). While no other studies have used ihMT to probe white matter development, previous MT studies have found slight decreases or no change in MTR during adolescence (Moura et al, ; Pangelinan et al, ; Perrin et al, ).…”

“…Histological research has revealed that myelination continues throughout adolescence (Benes, ; Yakovlev & Lecours, ), thus it remains possible that MT and ihMT measures applied to date have lacked the sensitivity required to describe myelination during this period. Optimizations to ihMT methods have been identified which may enable future studies to address myelination trajectories during adolescence with greater clarity (McHinda et al, ; Prevost et al, ). When considered together, our VF m and qihMT findings suggest that myelin sheaths may be incorporating more water between a relatively stable number of wrapped membranes during adolescence.…”

Whole brain inhomogeneous magnetization transfer (ihMT) imaging: Sensitivity enhancement within a steady‐state gradient echo sequence

“…) teaches us that increasing RF power becomes counterproductive above a certain point, and interleaving mixing periods with short saturation bursts allows a more efficient use of available RF energy. This effect was actually not initially expected because free relaxation periods were considered counterproductive for ihMT signal buildup because of the short lifetime of dipolar order, as in the case of long interpulse delays (i.e., long Δt) . Numerical simulations confirmed the optimal TR value's sensitivity, not only to T 1D but also to the exchange rate R, which taken together could explain the higher optimal TR values observed for simulations.…”

Region‐specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer)

“…The ihMT technique provides a new means to enhance the selectivity of MRI by properly weighting the signal to a specific T 1D range. Hence, thanks to its long T 1D , the dipolar order contribution of the myelinated structures can be isolated from the broad MT signal, giving rise to an enhanced myelinated tissue contrast relative to conventional MT . Although extensive work is still ongoing for the full characterization of this technique, it has already been used to assess brain and SC tissue demyelination in normal aging and multiple sclerosis .…”