Evaluation of Amyotrophic Lateral Sclerosis-Induced Muscle Degeneration Using Magnetic Resonance-Based Relaxivity Contrast Imaging (RCI)

Abstract

(1) Background: This work characterizes the sensitivity of magnetic resonance-based Relaxivity Contrast Imaging (RCI) to Amyotrophic Lateral Sclerosis (ALS)-induced changes in myofiber microstructure. Transverse Relaxivity at Tracer Equilibrium (TRATE), an RCI-based parameter, was evaluated in the lower extremities of ALS patients and healthy subjects. (2) Methods: In this IRB-approved study, 23 subjects (12 ALS patients and 11 healthy controls) were scanned at 3T (Philips, The Netherlands). RCI data were obtained during injection of a gadolinium-based contrast agent. TRATE, fat fraction and T2 measures, were compared in five muscle groups of the calf muscle, between ALS and control populations. TRATE was also evaluated longitudinally (baseline and 6 months) and was compared to clinical measures, namely ALS Functional Rating Scale (ALSFRS-R) and Hand-Held Dynamometry (HHD), in a subset of the ALS population. (3) Results: TRATE was significantly lower (p < 0.001) in ALS-affected muscle than in healthy muscle in all muscle groups. Fat fraction differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.01), tibialis posterior (p = 0.004), and peroneus longus (p = 0.02) muscle groups but were not statistically significant for the medial (p = 0.07) and lateral gastrocnemius (p = 0.06) muscles. T2 differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.004), peroneus longus (p = 0.004) and lateral gastrocnemius (p = 0.03) muscle groups but were not statistically significant for the tibialis posterior (p = 0.06) and medial gastrocnemius (p = 0.07) muscles. Longitudinally, TRATE, averaged over all patients, decreased by 28 ± 16% in the tibialis anterior, 47 ± 18% in the peroneus longus, 25 ± 19% in the tibialis posterior, 29 ± 14% in the medial gastrocnemius and 35 ± 18% in the lateral gastrocnemius muscles between two timepoints. ALSFRS-R scores were stable in two of four ALS patients. HHD scores decreased in three of four ALS patients. (4) Conclusion: RCI-based TRATE was shown to consistently differentiate ALS-affected muscle from healthy muscle and also provide a quantitative measure of longitudinal muscle degeneration.

Quantitative MRI Analysis of Brachial Plexus and Limb‐Girdle Muscles in Upper Extremity Onset Amyotrophic Lateral Sclerosis

“…Fat quantification based on the Dixon sequence is widely used to objectively assess the extent of fat infiltration into soft tissues 17,38 . We discovered that patients with ALS had significantly increased FF in the SSC, SSP, and ISP muscles, which is consistent with previous findings 15,39,40 . Increased FF, an indicator of increased fat infiltration in muscles, may reflect muscle steatosis, and is a valuable index for detecting ALS.…”

“…17,38 We discovered that patients with ALS had significantly increased FF in the SSC, SSP, and ISP muscles, which is consistent with previous findings. 15,39,40 Increased FF, an indicator of increased fat infiltration in muscles, may reflect muscle steatosis, and is a valuable index for detecting ALS. Our study also found a significantly lower CSA in the limb girdle muscles of patients with ALS, indicating the presence of muscle atrophy, 27 which may be related to muscle denervation due to dysfunctional neuromuscular connections.…”