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.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive death of upper motor neurons (UMNs) of the primary motor cortex and corticospinal tract (CST), in conjunction with lower motor neurons (LMNs) associated with the anterior horns
We have demonstrated a quantitative approach to consistently differen tiate ALS-affected calf muscle from healthy muscle by comparing Transverse Relaxivity at Tracer Equilibrium (TRATE), fat fraction, an relaxometry derived T2 values
We have demonstrated a quantitative approach to consistently differentiate ALS-affected calf muscle from healthy muscle by comparing TRATE, fat fraction, and relaxometry derived T2 values
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive death of upper motor neurons (UMNs) of the primary motor cortex and corticospinal tract (CST), in conjunction with lower motor neurons (LMNs) associated with the anterior horns. Despite the recognition of UMN and LMN involvement as a characteristic signature, the mean diagnostic delay among ALS patients is around 12 months, primarily due to patients being misdiagnosed with more common diseases that might mimic the early stages of ALS [1]. The long diagnostic delay underscores the dearth of robust and sensitive clinical biomarkers in ALS. Clinical indicators of disease status, such as Revised ALS Functional Rating Scale (ALSFRS-R), electromyography (EMG), and muscle strength tests, may be confounded by inter-rater variability and/or low sensitivity to ALS; these factors are further compounded by the clinical heterogeneity of disease onset and progression. There is an urgent need to establish robust, non-invasive, and quantitative biomarkers that can serve as early and specific diagnostic and prognostic indicators of disease
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