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The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development., (© 2024. The Author(s).)

Background: The use of advanced magnetic resonance imaging (MRI) techniques in MS research has led to new insights in lesion evolution and disease outcomes. It has not yet been determined if, or how, pre-lesional abnormalities in normal-appearing white matter (NAWM) relate to the long-term evolution of new lesions., Objective: To investigate the relationship between abnormalities in MRI measures of axonal and myelin volume fractions (AVF and MVF) in NAWM preceding development of black-hole (BH) and non-BH lesions in people with MS., Methods: We obtained magnetization transfer and diffusion MRI at 6-month intervals in patients with MS to estimate MVF and AVF during lesion evolution. Lesions were classified as either BH or non-BH on the final imaging visit using T 1 maps., Results: Longitudinal data from 97 new T 2 lesions from 9 participants were analyzed; 25 lesions in 8 participants were classified as BH 6-12 months after initial appearance. Pre-lesion MVF, AVF, and MVF/AVF were significantly lower, and T 1 was significantly higher, in the lesions that later became BHs ( p  < 0.001) compared to those that did not. No significant pre-lesion abnormalities were found in non-BH lesions ( p  > 0.05)., Conclusion: The present work demonstrated that pre-lesion abnormalities are associated with worse long-term lesion-level outcome.

Background: Wave-CAIPI Visualization of Short Transverse relaxation time component (ViSTa) is a recently developed, short-T 1 -sensitized MRI method for fast quantification of myelin water fraction (MWF) in the human brain. It represents a promising technique for the evaluation of subtle, early signals of demyelination in the cerebral white matter of multiple sclerosis (MS) patients. Currently however, few studies exist that robustly assess the utility of ViSTa MWF measures of myelin compared to more conventional MRI measures of myelin in the brain of MS patients. Moreover, there are no previous studies evaluating the sensitivity of ViSTa MWF for the non-invasive detection of subtle tissue damage in both normal-appearing white matter (NAWM) and white matter lesions of MS patients. As a result, a central purpose of this study was to systematically evaluate the relationship between myelin sensitivity of T 1 -based ViSTa MWF mapping and a more generally recognized metric, Magnetization Transfer Saturation (MT sat ), in healthy control and MS brain white matter., Methods: ViSTa MWF and MT sat values were evaluated in automatically-classified normal appearing white matter (NAWM), white matter (WM) lesion tissue, cortical gray matter, and deep gray matter of 29 MS patients and 10 healthy controls using 3T MRI. MWF and MT sat were also assessed in a tract-specific manner using the Johns Hopkins University WM atlas. MRI-derived measures of cerebral myelin content were uniquely compared by employing non-normal distribution-specific measures of median, interquartile range and skewness. Separate analyses of variance were applied to test tissue-specific differences in MT sat and ViSTa MWF distribution metrics. Non-parametric tests were utilized when appropriate. All tests were corrected for multiple comparisons using the False Discovery Rate method at the level, α=0.05., Results: Differences in whole NAWM MS tissue damage were detected with a higher effect size when using ViSTa MWF (q = 0.0008; ƞ 2  = 0.34) compared to MT sat (q = 0.02; ƞ 2 = 0.24). We also observed that, as a possible measure of WM pathology, ViSTa-derived NAWM MWF voxel distributions of MS subjects were consistently skewed towards lower MWF values, while MT sat voxel distributions showed reduced skewness values. We further identified tract-specific reductions in mean ViSTa MWF of MS patients compared to controls that were not observed with MT sat . However, MT sat (q = 1.4 × 10 -21 ; ƞ 2 = 0.88) displayed higher effect sizes when differentiating NAWM and MS lesion tissue. Using regression analysis at the group level, we identified a linear relationship between MT sat and ViSTa MWF in NAWM (R 2  = 0.46; p = 7.8 × 10 -4 ) lesions (R 2  = 0.30; p = 0.004), and with all tissue types combined (R 2  = 0.71; p = 8.4 × 10 -45 ). The linear relationship was also observed in most of the WM tracts we investigated. ViSTa MWF in NAWM of MS patients correlated with both disease duration (p = 0.02; R 2  = 0.27) and WM lesion volume (p = 0.002; R 2  = 0.34)., Conclusion: Because ViSTa MWF and MT sat metrics exhibit differential sensitivities to tissue damage in MS white matter, they can be collected in combination to provide an efficient, comprehensive measure of myelin water and macromolecular pool proton signals. These complementary measures may offer a more sensitive, non-invasive biopsy of early precursor signals in NAWM that occur prior to lesion formation. They may also aid in monitoring the efficacy of remyelination therapies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Most voxels in white matter contain multiple fiber populations with different orientations and levels of myelination. Conventional T 1 mapping measures 1 T 1 value per voxel, representing a weighted average of the multiple tract T 1 times. Inversion-recovery diffusion-weighted imaging (IR-DWI) allows the T 1 times of multiple tracts in a voxel to be disentangled, but the scan time is prohibitively long. Recently, slice-shuffled IR-DWI implementations have been proposed to significantly reduce scan time. In this work, we demonstrate that we can measure tract-specific T 1 values in the whole brain using simultaneous multi-slice slice-shuffled IR-DWI at 3T., Methods: We perform simulations to evaluate the accuracy and precision of our crossing fiber IR-DWI signal model for various fiber parameters. The proposed sequence and signal model are tested in a phantom consisting of crossing asparagus pieces doped with gadolinium to vary T 1 , and in 2 human subjects., Results: Our simulations show that tract-specific T 1 times can be estimated within 5% of the nominal fiber T 1 values. Tract-specific T 1 values were resolved in subvoxel 2 fiber crossings in the asparagus phantom. Tract-specific T 1 times were resolved in 2 different tract crossings in the human brain where myelination differences have previously been reported; the crossing of the cingulum and genu of the corpus callosum and the crossing of the corticospinal tract and pontine fibers., Conclusion: Whole-brain tract-specific T 1 mapping is feasible using slice-shuffled IR-DWI at 3T. This technique has the potential to improve the microstructural characterization of specific tracts implicated in neurodevelopment, aging, and demyelinating disorders., (© 2021 International Society for Magnetic Resonance in Medicine.)

The fiber g-ratio is the ratio of the inner to the outer diameter of the myelin sheath of a myelinated axon. It has a limited dynamic range in healthy white matter, as it is optimized for speed of signal conduction, cellular energetics, and spatial constraints. In vivo imaging of the g-ratio in health and disease would greatly increase our knowledge of the nervous system and our ability to diagnose, monitor, and treat disease. MRI based g-ratio imaging was first conceived in 2011, and expanded to be feasible in full brain white matter with preliminary results in 2013. This manuscript reviews the growing g-ratio imaging literature and speculates on future applications. It details the methodology for imaging the g-ratio with MRI, and describes the known pitfalls and challenges in doing so., (Copyright © 2017 Elsevier Inc. All rights reserved.)