Tract-specific analysis improves sensitivity of spinal cord diffusion MRI to cross-sectional and longitudinal changes in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord. Corticospinal tract degeneration is a defining feature of ALS. However, there have been very few longitudinal, controlled studies assessing diffusion MRI (dMRI) metrics in different fiber tracts along the spinal cord in general or the corticospinal tract in particular. Here we demonstrate that a tract-specific analysis, with segmentation of ascending and descending tracts in the spinal cord white matter, substantially increases the sensitivity of dMRI to disease-related changes in ALS. Our work also identifies the tracts and spinal levels affected in ALS, supporting electrophysiologic and pathologic evidence of involvement of sensory pathways in ALS. We note changes in diffusion metrics and cord cross-sectional area, with enhanced sensitivity to disease effects through a multimodal analysis, and with strong correlations between these metrics and spinal components of ALSFRS-R.

Tract‐Specific Spinal Cord Diffusion Tensor Imaging in Friedreich's Ataxia

“…A similar observation was recognized in longitudinal spinal cord DTI analyses in ALS, where authors found longitudinal changes only in more inferior spinal levels, suggesting, therefore, a dying-forward mechanism. 19 Our findings also correlate with the late presentation of upper motor neuron signs (such as weakness and spasticity) in FRDA patients. Nevertheless, it is important to highlight that our findings were limited to a cross-sectional analysis and further longitudinal studies are required to confirm these hypotheses, as well as to evaluate whether these results are reproducible and applicable to other segments of the spinal cord.…”

“…Recently, specific DTI protocols for the spinal cord were developed and proved sensitive to detect abnormalities in several conditions, such as adrenoleukodystrophy, 11,12 Hirayama disease, 13 amyotrophic lateral sclerosis (ALS), 14,15 multiple sclerosis 16,17 as well as traumatic and non‐traumatic spinal cord injury 18 . Additionally, analysis of individual fiber tracts, referred to as tract‐specific DTI analysis, has been used to increase the sensitivity of spinal cord imaging to capture longitudinal changes in conditions such as ALS 19 …”

Spinal cord MRI and MRS Detect Early-stage Alterations and Disease Progression in Friedreich Ataxia

“…From these pairs the susceptibility-induced off-resonance field was estimated and corrected using a method similar to that described in 37 . Subject motion and eddy-current induced distortions were corrected 38 as previously reported 23 .…”

“…Diffusion tensor imaging (DTI) models diffusion MRI data by assuming Gaussian diffusion at each location of the imaged tissue. Diffusion MRI of the spinal cord is challenging and has only recently received growing attention and seen new developments in the neuroimaging community 20-26 , with applications in disorders such as degenerative cord compression 27 , multiple sclerosis 28 , amyotrophic lateral sclerosis 23 and traumatic spinal cord injury 29 . To the best of our knowledge, only one study has reported cross-sectional data using dMRI in the spinal cord in FRDA 30 , and no longitudinal dMRI data have been published.…”

HARDI-ZOOMit protocol improves specificity to microstructural changes in presymptomatic myelopathy

“…Although C3–C6 WM or GM ROIs are quite large and coarse, it is feasible to proceed to finer analysis of tract-specific dMRI metrics utilizing a template and tract-specific atlas co-registration 37 , 40 . Tract-specific changes within our studied group of patients might be investigated, as demonstrated in the case of DCM 41 – 43 or ALS 44 patients.…”