Measuring longitudinal myelin water fraction in new multiple sclerosis lesions

Abstract

ObjectivesInvestigating the potential of myelin repair strategies in multiple sclerosis (MS) requires an understanding of myelin dynamics during lesion evolution. The objective of this study is to longitudinally measure myelin water fraction (MWF), an MRI biomarker of myelin, in new MS lesions and to identify factors that influence their subsequent myelin content.MethodsTwenty-three MS patients were scanned with whole-brain Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) MWF mapping at baseline and median follow-up of 6 months. Eleven healthy controls (HC) confirmed the reproducibility of FAST-T2 in white matter regions of interests (ROIs) similar to a lesion size. A random-effect-model was implemented to determine the association between baseline clinical and lesion variables and the subsequent MWF.ResultsROI-based measurements in HCs were highly correlated between scans [mean r = 0.893 (.764–.967)]. In MS patients, 38 gadolinium enhancing (Gd+) and 25 new non-enhancing (Gd−) T2 hyperintense lesions (5.7 months, ±3.8) were identified. Significant improvement in MWF was seen in Gd+ lesions (0.035 ± 0.029, p < 0.001) as compared to Gd− lesions (0.006 ± 0.017, p = 0.065). In the model, a higher baseline MWF (p < 0.001) and the presence of Gd (p < 0.001) were associated with higher subsequent MWF.ConclusionsFAST T2 provides a clinically feasible method to quantify MWF in new MS lesions. The observed influence of baseline MWF, which represents a combined effect of both resolving edema and myelin change within acute lesions, suggests that the extent of initial inflammation impacts final myelin recovery.

Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions

“…For quantitative assessment of tissue damage in white matter MS lesions, MWF is regarded as an indirect measure of myelin with a relatively high specificity given the strong pathological correlation. 26–28 We recognize that an increase susceptibility within a chronic lesion can be due to demyelination or iron deposition, which limits direct iron quantification by QSM. 17 We identify QSM rim+ lesions as having a rim of iron based upon the susceptibility gradient between the rim and core regions.…”

“…MWF is a well-validated quantitative MRI biomarker for myelin, 26, 27 which can be mapped efficiently and reproducibly with FAST-T2. 25, 28 The QSM0 algorithm improves QSM zero reference selection by enforcing susceptibility homogeneity of CSF within the brain ventricles and eliminating the need for manual drawing of CSF region-of-interest (ROI). QSM0 and MWF were used to identify MS lesions with a hyperintense rim pattern consistent with iron deposition and to assess the extent of myelin damage found within these lesions.…”

Myelin water imaging to detect demyelination and remyelination and its validation in pathology

“…mcDESPOT-derived MWF shows a positive correlation between physical activity level and MWF in the right parahippocampal cingulum (16) and one study found regional differences in MWF of the corpus callosum between males and females (91). Reproducibility and reliability of MWF in healthy controls, both at a single site and multiple sites is very good (14,103,171,174).…”

Brain Myelin Water Fraction and Diffusion Tensor Imaging Atlases for 9‐10 Year‐Old Children

“…Myelin water fraction (MWF), defined as the fraction of the total signal which has T 2 < 40 milliseconds at 3 Tesla, has been histologically validated as a marker of myelin density in human tissue, 30–32 and has good scan‐rescan reproducibility (coefficient of variation 4% in cerebral white matter) 33 . MWI has been used to investigate myelin in a wide range of diseases including multiple sclerosis, neuromyelitis optica spectrum disorder, schizophrenia, Niemann‐Pick disease, prenatal alcohol exposure, amyotrophic and primary lateral sclerosis, Krabbe disease, autism, stroke, and traumatic brain injury 34–47 . Rapid myelination has been demonstrated in early childhood and adolescence using multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT), an alternate approach to MWI using a steady‐state acquisition 48–53 .…”

“…33 MWI has been used to investigate myelin in a wide range of diseases including multiple sclerosis, neuromyelitis optica spectrum disorder, schizophrenia, Niemann-Pick disease, prenatal alcohol exposure, amyotrophic and primary lateral sclerosis, Krabbe disease, autism, stroke, and traumatic brain injury. [34][35][36][37][38][39][40][41][42][43][44][45][46][47] Rapid myelination has been demonstrated in early childhood and adolescence using multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT), an alternate approach to MWI using a steadystate acquisition. [48][49][50][51][52][53] Adult multi-echo T 2 -based MWF atlases in both brain and cervical spinal cord have recently been published, 54,55 but, to our knowledge, no such atlases exist for children.…”