Abstract
Background: Biomarkers of disease progression and outcome measures are still lacking for patients with amyotrophic lateral sclerosis (ALS). Muscle MRI can be a promising candidate to track longitudinal changes and to predict response to the therapy in clinical trials.Objective: Our aim is to apply quantitative muscle MRI in the evaluation of disease progression, focusing on thigh and leg muscles of patients with ALS, and to explore the correlation between radiological and clinical scores.Methods: We enrolled newly diagnosed patients with ALS, longitudinally scored using the ALS Functional Rating Scale-Revised (ALSFRS-R), who underwent a 3T muscle MRI protocol including a 6-point Dixon gradient-echo sequence and multi-echo turbo spin echo (TSE) T2-weighted sequence for quantification of fat fraction (FF), cross-sectional area (CSA), and water T2 (wT2). A total of 12 muscles of the thigh and six muscles of the leg were assessed by the manual drawing of 18 regions of interest (ROIs), for each side. A group of 11 age-matched healthy controls (HCs) was enrolled for comparison.Results: 15 patients (M/F 8/7; mean age 62.2 years old, range 29–79) diagnosed with possible (n = 2), probable (n = 12), or definite (n = 1) ALS were enrolled. Eleven patients presented spinal onset, whereas four of them had initial bulbar involvement. All patients performed MRI at T0, nine of them at T1, and seven of them at T2. At baseline, wT2 was significantly elevated in ALS subjects compared to HCs for several muscles of the thigh and mainly for leg muscles. By contrast, FF was elevated in few muscles, and mainly at the level of the thigh. The applied mixed effects model showed that FF increased significantly in the leg muscles over time (mainly in the triceps surae) and that wT2 decreased significantly in line with worsening in the leg subscore of ALSFRS-R, mainly at the leg level and in the anterior and medial compartment of the thigh.Conclusions: Quantitative MRI represents a non-invasive tool that is able to outline the trajectory of pathogenic modifications at the muscle level in ALS. In particular, wT2 was found to be increased early in the clinical history of ALS and also tended to decrease over time, also showing a positive correlation with leg subscore of ALSFRS-R.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that targets motor neurons, though other cells may be affected as well
As for T2 times, a study by Jenkins et al found that T2 signal was increased in ALS subjects compared to controls, with muscle differences as low as 0.6% and as high as 71.4% for tibialis anterior (TA); T2 signal increased over time in ALS subjects at 4-month follow-up for TA [3]
When evaluating the evolution of quantitative MRI (qMRI) measures over time, we found that water T2 (wT2) decreased significantly over time only in the gemellus medialis and peroneal muscles
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that targets motor neurons, though other cells (including muscle cells) may be affected as well. Quantitative muscle MRI has been proposed and successfully used to provide biomarkers for tracking disease evolution and, when available, assess response to treatment in neuromuscular disorders [8,9,10,11] and for ALS [12]. In a more recent study, T2 increased at 12-month follow-up for right TA, right quadriceps, bilateral hamstrings, and gastrocnemius/soleus (by a 14–29%) [4]. They found that increase in T2 signal after 1 year correlated with progressive weakness and with the loss of motor units at EMG [4]. Muscle MRI can be a promising candidate to track longitudinal changes and to predict response to the therapy in clinical trials
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