Deficient MWF mapping in multiple sclerosis using 3D whole-brain multi-component relaxation MRI

Abstract

Recent multiple sclerosis (MS) MRI research has highlighted the need to move beyond the lesion-centric view and to develop and validate new MR imaging strategies that quantify the invisible burden of disease in the brain and establish much more sensitive and specific surrogate markers of clinical disability. One of the most promising of such measures is myelin-selective MRI that allows the acquisition of myelin water fraction (MWF) maps, a parameter that is correlated to brain white matter (WM) myelination. The aim of our study was to apply the newest myelin-selective MRI method, multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) in a controlled clinical MS pilot trial. This study was designed to assess the capabilities of this new method to explain differences in disease course and degree of disability in subjects spanning a broad spectrum of MS disease severity. The whole-brain isotropically-resolved 3D acquisition capability of mcDESPOT allowed for the first time the registration of 3D MWF maps to standard space, and consequently a formalized voxel-based analysis of the data. This approach combined with image segmentation further allowed the derivation of new measures of MWF deficiency: total deficient MWF volume (DV) in WM, in WM lesions, in diffusely abnormal white matter and in normal appearing white matter (NAWM). Deficient MWF volume fraction (DVF) was derived from each of these by dividing by the corresponding region volume. Our results confirm that lesion burden does not correlate well with clinical disease activity measured with the extended disability status scale (EDSS) in MS patients. In contrast, our measurements of DVF in NAWM correlated significantly with the EDSS score (R2 = 0.37; p < 0.001). The same quantity discriminated clinically isolated syndrome patients from a normal control population (p < 0.001) and discriminated relapsing–remitting from secondary-progressive patients (p < 0.05); hence this new technique may sense early disease-related myelin loss and transitions to progressive disease. Multivariate analysis revealed that global atrophy, mean whole-brain myelin water fraction and white matter atrophy were the three most important image-derived parameters for predicting clinical disability (EDSS). Overall, our results demonstrate that mcDESPOT-defined measurements in NAWM show great promise as imaging markers of global clinical disease activity in MS. Further investigation will determine if this measure can serve as a risk factor for the conversion into definite MS and for the secondary transition into irreversible disease progression.

Improved determination of the myelin water fraction in human brain using magnetic resonance imaging through Bayesian analysis of mcDESPOT

“…Similarly, T 2 and Δω * TR maps were then generated according to the DESPOT 2 -FM method (36) by fitting the bSSFP datasets as a function of FA to a single component form of the signal, using the voxel-wise B 1 and T 1 values obtained as outlined above. Finally, the Δω * TR and B 1 maps, combined with the SPGR and bSSFP datasets, were used to generate f s maps reflecting MWF (18-23). …”

“…mcDESPOT has been applied to map MWF in human brain (19-23) with data acquisition sufficiently rapid to permit whole brain coverage. However, Bouhrara et al .…”

White matter development and early cognition in babies and toddlers

“…An emerging MCR approach, multicomponent Driven Equilibrium Single Pulse Observation of T 1 and T 2 (mcDESPOT), offers potential advantages over conventional MCR approaches, namely decreased acquisition times, increased volumetric coverage (i.e., whole-brain), and improved spatial resolution. Though mcDESPOT myelin water fraction measures (denoted VF M to distinguish from conventional MWF) are consistently larger than corresponding MWF values, they correspond qualitatively with histological myelin content measures in an animal model of dysmyelination [Hurley et al, 2010], and reflect the disease course and clinical variability in multiple sclerosis [Kitzler et al, 2012; Kolind et al, 2012] and other demyelinating disorders [Kolind et al, 2013]. …”

Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease

“…An imaging technique called mcDESPOT 18 (multi-component Driven Equilibrium Single Pulse Observation of T1 and T2) was used to assess regional myelin water fraction (MWF), a quantitative measure sensitive to myelin that we have previously used to investigate infant brain development 18,19 and demyelinating disorders such as multiple sclerosis. 20,21 Prior mcDESPOT investigations of white matter development throughout infancy and early childhood have mirrored the histologically established spatiotemporal pattern of myelination, 22 and histological comparisons in a dysmyelinating “shaking-pup” model 23 have demonstrated the method’s sensitivity and specificity to detect myelin. Automated voxel-based image-analysis algorithms were used to compare regional MWF and GMV to characterize and compare age-related trajectories in the 2- to 25-month-old ε4 carrier and noncarrier groups.…”