T_1D‐weighted ihMT imaging – Part II. Investigating the long‐ and short‐T_1D components correlation with myelin content. Comparison with R₁ and the macromolecular proton fraction

Abstract

To investigate the long-and short-T 1D components correlation with myelin content using inhomogeneous magnetization transfer (ihMT) high-pass and band-pass T 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 1Dfilters is proposed as an MRI biomarker for myelin content. Future studies should | METHODS | Animal experimentsAnimal studies were conducted in agreement with the French guidelines for animal care from the French Department of Agriculture (Animal Rights Division), the directive 2010/63/EU of the European Parliament and of enable the investigation of the sensitivity of ihMT T 1D -filters for demyelinating processes.

T1D‐weighted ihMT imaging – Part I. Isolation of long‐ and short‐T1D components by T1D‐filtering

“…A detailed analysis on the explored filters’ selectivity to certain T 1D components and their impact on the specificity and sensitivity of ihMT to myelin concerns the Part II of this work 43 …”

Inhomogeneous Magnetization Transfer (ihMT) imaging in the acute cuprizone mouse model of demyelination/remyelination

“…A comprehensive theoretical and experimental analysis of the T 1D -weighting associated with ihMT was described and allowed the generation of high-pass and band-pass T 1D -filters dedicated to brain tissues ( Hertanu et al, 2022a ). Furthermore, a second study performed on healthy mice focused on the validation of the sensitivity and specificity to myelination of these T 1D -filters by comparing brain ihMT MRI data with histology ( Hertanu et al, 2022b ). Consistent with a dominant contribution of the long T 1D component in myelin, high specificity to healthy myelinated tissues was obtained for the high-pass T 1Dfilter selective for the long T 1D component.…”

“…• TA = 4 min 32 s • TA = 9 min 30 s • TA = 1 min 59 s T 2 -weighted (T 2 w) anatomical images were acquired along with specific sequences for the generation of the semi-quantitative and quantitative metrics of interest to assess myelination: ihMTsat, MPF and R 1 . The protocols have been thoroughly described in previous work ( Hertanu et al, 2022b ). In brief, a slab-selective 3D low duty cycle Mchinda et al, 2018 ) ihMT rapid gradient echo (ihMTRAGE) ( Varma et al, 2020 ) sequence was used with various values of the dual-frequency offset switching time ( ∆t) (see Fig.…”

“…Consistent with a dominant contribution of the long T 1D component in myelin, high specificity to healthy myelinated tissues was obtained for the high-pass T 1Dfilter selective for the long T 1D component. In addition an increasing trend in specificity was noticed as the ihMT T 1D -filter was weighted towards longer T 1D ranges by Δt lengthening ( Duhamel et al, 2019 ;Hertanu et al, 2022b ). In contrast, for the band-pass T 1D -filter isolating short T 1D components in the 100 μs to 1 ms range, lower specificity and poor correlation with histology myelin biomarkers suggested a dominant contribution of non-myelin signal source ( Hertanu et al, 2022b ).…”

“…In addition an increasing trend in specificity was noticed as the ihMT T 1D -filter was weighted towards longer T 1D ranges by Δt lengthening ( Duhamel et al, 2019 ;Hertanu et al, 2022b ). In contrast, for the band-pass T 1D -filter isolating short T 1D components in the 100 μs to 1 ms range, lower specificity and poor correlation with histology myelin biomarkers suggested a dominant contribution of non-myelin signal source ( Hertanu et al, 2022b ). Therefore, by providing access to different microstructural tissue components and features, ihMT might allow the evaluation of distinct biophysical mechanisms underlying myelin pathology.…”