Relaxometry and brain myelin quantification with synthetic MRI in MS subtypes and their associations with spinal cord atrophy

• Published in: NeuroImage clinical Vol. 36; p. 103166
• Main Authors: Ladopoulos, Theodoros, Matusche, Britta, Bellenberg, Barbara, Heuser, Florian, Gold, Ralf, Lukas, Carsten, Schneider, Ruth
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2022; Elsevier
• Subjects: Atrophy - pathology; Brain - diagnostic imaging; Brain - pathology; Cross-Sectional Studies; Humans; Magnetic Resonance Imaging - methods; MRI; Multiple Sclerosis; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - pathology; Myelin imaging; Myelin Sheath - pathology; Protons; Radiology; Regular; Relaxation times; Spinal Cord - diagnostic imaging; Spinal Cord - pathology; Spinal cord atrophy; Synthetic MR; RRMS; PPMS; iMVF; MRI; Myelin imaging; Multiple Sclerosis; aMVF; QRAPMASTER; WM; CSF; Spinal cord atrophy; MUCCA; EDSS; GMF; SPMS; GM; MS; DGM; NAWM; ROI; Relaxation times; CS; WMF; PMS; Synthetic MR; BPF; MVF; ICV; Multiple sclerosis; mean upper cervical cord area; control subjects; grey matter fraction; expanded disability status scale; secondary progressive multiple sclerosis; relapsing remitting multiple sclerosis; intracranial myelin volume fraction; progressive multiple sclerosis; primary progressive multiple sclerosis; quantification of relaxation times and proton density by multi-echo acquisition of a saturation recovery using turbo spin-echo readout; cerebrospinal fluid; myelin volume fraction; magnetic resonance imaging; normal appearing white matter; average myelin volume fraction; white matter; grey matter; white matter fraction; deep grey matter; intracranial volume; region of interest; brain parenchymal fraction
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2022.103166

•Synthetic MR was able to quantify differences on MVF, R1, R2 and PD between patients with MS and CS.•Intracranial MVF has a greater impact on spinal cord volume loss compared to BPF or total brain lesion load.•MUCCA was associated with supratentorial demyelination as a result of diffuse disease activity.•Alterations in R1, R2 and PD in adjacent infratentorial ROIs were associated with spinal cord atrophy. Immune-mediated demyelination and neurodegeneration are pathophysiological hallmarks of Multiple Sclerosis (MS) and main drivers of disease related disability. The principal method for evaluating qualitatively demyelinating events in the clinical context is contrast-weighted magnetic resonance imaging (MRI). Moreover, advanced MRI sequences provide reliable quantification of brain myelin offering new opportunities to study tissue pathology in vivo. Towards neurodegenerative aspects of the disease, spinal cord atrophy – besides brain atrophy – is a powerful and validated predictor of disease progression. The etiology of spinal cord volume loss is still a matter of research, as it remains unclear whether the impact of local lesion pathology or the interaction with supra- and infratentorial axonal degeneration and demyelination of the long descending and ascending fiber tracts are the determining factors. Quantitative synthetic MR using a multiecho acquisition of saturation recovery pulse sequence provides fast automatic brain tissue and myelin volumetry based on R1 and R2 relaxation rates and proton density quantification, making it a promising modality for application in the clinical routine. In this cross sectional study a total of 91 MS patients and 31 control subjects were included to investigate group differences of global and regional measures of brain myelin and relaxation rates, in different MS subtypes, using QRAPMASTER sequence and SyMRI postprocessing software. Furthermore, we examined associations between these quantitative brain parameters and spinal cord atrophy to draw conclusions about possible pathophysiological relationships. Intracranial myelin volume fraction of the global brain exhibited statistically significant differences between control subjects (10.4%) and MS patients (RRMS 9.4%, PMS 8.1%). In a LASSO regression analysis with total brain lesion load, intracranial myelin volume fraction and brain parenchymal fraction, the intracranial myelin volume fraction was the variable with the highest impact on spinal cord atrophy (standardized coefficient 4.52). Regional supratentorial MRI metrics showed altered average myelin volume fraction, R1, R2 and proton density in MS patients compared to controls most pronounced in PMS. Interestingly, quantitative MRI parameters in supratentorial regions showed strong associations with upper cord atrophy, suggesting an important role of brain diffuse demyelination on spinal cord pathology possibly in the context of global disease activity. R1, R2 or proton density of the thalamus, cerebellum and brainstem correlated with upper cervical cord atrophy, probably reflecting the direct functional connection between these brain structures and the spinal cord as well as the effects of retrograde and anterograde axonal degeneration. By using Synthetic MR-derived myelin volume fraction, we were able to effectively detect significant differences of myelination in relapsing and progressive MS subtypes. Total intracranial brain myelin volume fraction seemed to predict spinal cord volume loss better than brain atrophy or total lesion load. Furthermore, demyelination in highly myelinated supratentorial regions, as an indicator of diffuse disease activity, as well as alterations of relaxation parameters in adjacent infratentorial and midbrain areas were strongly associated with upper cervical cord atrophy.