Laule, Cornelia; Cohen-Adad, Julien; Witt, Atlee A.; De Luca, Gabriele C.; Granziera, Cristina; Keegan, B. Mark; Kerbrat, Anne; Klawiter, Eric C.; Kolind, Shannon; O鈥橤rady, Kristin P.; Oh, Jiwon; Schilling, Kurt G.; Sivakolundu, Dinesh K.; Smith, Seth A.; Tozlu, Ceren; Vavasour, Irene M.; Bagnato, Francesca; Gauthier, Susan A.; Mainero, Caterina; Alonso-Ortiz, Eva; Bakshi, Rohit; Beck, Erin S.; Brier, Matthew R.; Hemond, Christopher C.; Krieger, Stephen; Li, David K. B.; Shinohara, Russell T.; Henry, Roland G. (2026).听.听Multiple Sclerosis Journal.听
The spinal cord plays an important role in multiple sclerosis, or MS, but it has not been studied as much as the brain. This review summarizes the main takeaways from a 2025 workshop on spinal cord imaging in MS, including recent progress, ongoing problems, and future directions. It explains how damage to the spinal cord, such as lesions and shrinkage, can help doctors diagnose MS, predict how the disease may progress, and monitor how well treatment is working. The review also highlights new markers that may help track disease worsening even when patients are not having relapses. Studies comparing magnetic resonance imaging, or MRI, with tissue samples and patient outcomes support the usefulness of newer spinal cord imaging methods. At the same time, the review notes that spinal cord imaging still faces technical challenges, including the need for better analysis pipelines and more consistent results across studies. Overall, the authors argue that advanced, quantitative spinal cord imaging should be used more widely in clinical trials, research, and, when possible, patient care, because it can help show the full extent of MS and improve outcomes.
Figure 1. Spinal cord pathological features and MRI-pathology correlations. (a) Lesion frequency heatmaps of total demyelinated lesions in the cervical (top), thoracic (middle), and lumbar (bottom) spinal cord. Lesion predilection sites include the dorsal columns, lateral columns, and gray matter as a whole, with relative sparing of the subpial surface. (b) Myelin (proteolipid protein) and (c) fibrin(ogen) immunostaining in adjacent spinal cord sections from an MS case. Fibrin(ogen) deposition is consistently found in the central part of the cord, including gray matter, and mesial aspects of the lateral columns and central part of the dorsal column in areas outside demyelinated lesions. (d) Hematoxylin and eosin鈥搒tained section with magnified inset (e), demonstrating thickened vasculature in the MS spinal cord, a finding consistently found in younger cases. Perivascular space dilatation is also a common feature (not shown). (f) and (g) Palmgren silver-stained sections showing reduced axonal density in an MS case (g) compared with control (f), with predilection for loss of small diameter axons. (h) Luxol Fast Blue stain for myelin and (i) Bielschowsky stain for axons in the secondary progressive MS section demonstrate reduced staining in a focal lesion (arrow), which is visualized on 7 Tesla ex vivo MRI as (j) T2-weighted hyperintensity and (k) myelin water fraction imaging hypointensity. Comparison between Luxol Fast Blue myelin staining optical density and quantitative MRI, (l) radial diffusivity (RD), (m) inhomogeneous magnetization transfer (ihMT) and (n) myelin water fraction (MWF) show strong quantitative correlations between histology and MRI markers for myelin in the spinal cord. (a) Adapted from Waldman et al.,聽Acta Neuropathol听2024; (f) and (g) adapted from DeLuca et al.,聽Brain听2004.