Magnetization transfer ratio: a quantitative imaging biomarker for 5q spinal muscular atrophy

In this exploratory study, we used magnetization transfer contrast (MTC) imaging, an MRI technique that provides information about protons bound to macromolecular structures such as myelin lipids or collagen, to quantify sciatic nerve lesions in patients with spinal muscular atrophy (SMA) 3a and 3b. Our results show that the calculated magnetization transfer ratio (MTR) reliably differentiated between healthy controls, SMA 3a, and SMA 3b, while correlating well with clinical scores and compound motor action potentials. MTR might become a new imaging biomarker that potentially helps to better monitor SMA patients on causative pharmacotherapies in the future. Background and purpose We quantified peripheral nerve lesions in adults with 5q‐linked spinal muscular atrophy (SMA) type 3 by analysing the magnetization transfer ratio (MTR) of the sciatic nerve, and tested its potential as a novel biomarker for macromolecular changes. Methods Eighteen adults with SMA 3 (50% SMA 3a, 50% SMA 3b) and 18 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging in a 3‐Tesla magnetic resonance scanner. Two axial three‐dimensional gradient echo sequences, with and without an off‐resonance saturation rapid frequency pulse, were performed at the right distal thigh. Sciatic nerve regions of interest were manually traced on 10 consecutive axial slices in the images generated without off‐resonance saturation, and then transferred to corresponding slices generated by the sequence with the off‐resonance saturation pulse. Subsequently, MTR and cross‐sectional areas (CSAs) of the sciatic nerve were analysed. In addition, detailed neurologic, physiotherapeutic and electrophysiologic examinations were conducted in all patients. Results Sciatic nerve MTR and CSA reliably differentiated between healthy controls and SMA 3, 3a or 3b. MTR was lower in the SMA 3 (P