Axonal water fraction as marker of white matter injury in primary‐progressive multiple sclerosis: a longitudinal study

Abstract

Background and purpose Diffuse white matter (WM) injury is prominent in primary‐progressive multiple sclerosis (PP‐MS) pathology and is a potential biomarker of disease progression. Diffusion kurtosis imaging allows the quantification of non‐Gaussian water diffusion, providing metrics with high WM pathological specificity. The aim of this study was to characterize the pathological changes occurring in the normal‐appearing WM of patients with PP‐MS at baseline and at 1‐year follow‐up and to assess their impact on disability and short‐term disease progression. Methods A total of 26 patients with PP‐MS and 20 healthy controls were prospectively enrolled. Diffusion kurtosis imaging single‐shot echo‐planar imaging (EPI) was acquired on a 3‐T scanner (Philips Achieva, Best, The Netherlands) (voxel size, 2 × 2 × 2 mm3, 30 directions for each b‐value = 1000, 2000 s/mm2 and one b = 0 s/mm2). A two‐compartment biophysical model of WM tract integrity was used to derive spatial maps of axonal water fraction (AWF), intra‐axonal diffusivity, extra‐axonal axial and radial diffusivities (De,axial, De,radial) and tortuosity from the following WM tracts: corpus callosum (CC), corticospinal tract (CST) and posterior thalamic radiation (PTR). Results At baseline, patients with PP‐MS showed a widespread decrease of AWF, tortuosity and De,axial and an increase of De,radial in CC, CST and PTR (P ranging from 0.001 to 0.036). At 1‐year follow‐up, a significant AWF decrease was detected in the body of CC (P = 0.048), PTR (P = 0.008) and CST (P = 0.044). Baseline AWF values in CST significantly discriminated progressed from non‐progressed patients (P = 0.021; area under the curve, 0.854). Conclusion Based on its change over time and its relationship with disease progression, among the analyzed metrics, AWF seems the most sensitive metric of WM tissue damage in PP‐MS and therefore it could be considered as a marker for monitoring disease progression.

Streamline density and lesion volume reveal a postero–anterior gradient of corpus callosum damage in multiple sclerosis

“…Over the last decades, the application of advanced neuroimaging techniques and new processing methods [1] has clarified that damage of specific white matter (WM) tracts contributes to different aspects of clinical disability in multiple sclerosis (MS) [2][3][4][5][6][7]. Amongst WM tracts, the corpus callosum (CC) is one of the preferential sites of clinically eloquent damage [4][5]8], since it is the target of both direct damage from focal lesions/diffuse neurodegenerative processes and indirect damage deriving from Wallerian degeneration of axons transected by hemispheric lesions [9].…”

Approximation to pain‐signaling network in humans by means of migraine

“…To assess functional fiber integrity, we relied on V intra , which corresponds to the AWF, a dMRI parameter derived from the NODDI technique (Zhang et al, 2012). Intra‐axonal volume/water is negatively correlated to fiber damage (By et al, 2017; Margoni et al, 2019), but positively correlated to efficacious neuronal function (Genç et al, 2018). To obtain functional proof that tracked fiber bundles are indeed involved in the processing of nociceptive signals, we correlated V intra with the self‐reported levels of recent pain experiences (NTPIS, (Cook et al, 2013)).…”

“…Among the mesoscopic dMRI parameters extracted by our Bayesian approach, the best measure of functional fiber integrity turned out to be the V intra that corresponds to the axonal water fraction (AWF) of NODDI. Indeed, a reduction in V intra was the most sensitive measure of white matter damage in the cervical spinal cord (By, Xu, Box, Bagnato, & Smith, 2017) and supratentorial fiber tracts (Margoni et al, 2019) of patients suffering from multiple sclerosis. In contrast, increased intra‐neurite volume within the gray matter was associated with higher intelligence (Genç et al, 2018).…”

Advanced Diffusion MR Imaging for Multiple Sclerosis in the Brain and Spinal Cord

“…Enthusiastic readers are referred to previous publications on this topic. 66,67 WMTI has been applied in clinical studies of MS, [68][69][70][71] and these studies suggested that a decrease in AWF in the white matter correlates with clinical disability, presumably reflecting chronic axonal loss. In animal models, WMTI has been shown to be capable of distinguishing different tissue pathologies in demyelinating lesions and tracking their longitudinal courses.…”