Region‐specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer)

Abstract

In this preliminary study, our objective was to investigate the potential of high-resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template-extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age-matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T *-weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R = -0.75, p = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p < 0.005), and λ (axial diffusivity) decreased significantly in CST (p = 0.0004) and PST (p = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < |R| < 0.87, p < 0.05). Altogether, these preliminary results suggest that high-resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.

Chitotriosidase, a biomarker of amyotrophic lateral sclerosis, accentuates neurodegeneration in spinal motor neurons through neuroinflammation

“…Conditioned medium from glial cells exposed to ALS-CSF also resulted in reduced viability of NSC-34 cells [31,41]. The reduction in the white matter area observed with staining by phospohorylated neurofilaments can be correlated to white matter atrophy observed in ALS patient spinal cord [49]. Based on these data, it could be assumed that CHIT-1 primarily activates microglia while astrocytes respond to activated microglia and join to evoke a sustained toxicity resulting in the release of proinflammatory molecules, which can further lead to neuronal death (Fig.…”

Evaluation of Intra‐ and Interscanner Reliability of MRI Protocols for Spinal Cord Gray Matter and Total Cross‐Sectional Area Measurements

“…The first approach is JIM v6 (Xinapse Systems, http://www.xinapse.com) that was previously used in different studies . The second approach is the open source Spinal Cord Toolbox (SCT) (https://sourceforge.net/p/spinalcordtoolbox/wiki/Home/) that has seen recent utilization …”

Validating the sensitivity of inhomogeneous magnetization transfer (ihMT) MRI to myelin with fluorescence microscopy

“…In addition to this strong contrast for myelinated tissues, the ihMT technique also benefits from trivial processing, simply based on the subtraction of a minimum of 2 MT images obtained with different radiofrequency (RF) irradiation parameters. Overall, these properties have made ihMT an attractive method to assess myelin-related information in vivo, in the clinical context of demyelinating diseases (Rasoanandrianina et al, 2017;Van Obberghen et al, 2018) or in the context of aging studies (Geeraert et al, 2017;Taso et al, 2016). In addition, other studies have shown that the ihMT signal correlates with established myelin-sensitive MR imaging techniques such as myelin water fraction (MWF) (Ercan et al, 2018;Geeraert et al, 2017).…”