Abstract
PurposeAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to neuromuscular palsy and death. We propose a computational approach to [18F]-fluorodeoxyglucose (FDG) PET/CT images to analyze the structure and metabolic pattern of skeletal muscle in ALS and its relationship with disease aggressiveness.Materials and methodsA computational 3D method was used to extract whole psoas muscle’s volumes and average attenuation coefficient (AAC) from CT images obtained by FDG PET/CT performed in 62 ALS patients and healthy controls. Psoas average standardized uptake value (normalized on the liver, N-SUV) and its distribution heterogeneity (defined as N-SUV variation coefficient, VC-SUV) were also extracted. Spinal cord and brain motor cortex FDG uptake were also estimated.ResultsAs previously described, FDG uptake was significantly higher in the spinal cord and lower in the brain motor cortex, in ALS compared to controls. While psoas AAC was similar in patients and controls, in ALS a significant reduction in psoas volume (3.6 ± 1.02 vs 4.12 ± 1.33 mL/kg; p < 0.01) and increase in psoas N-SUV (0.45 ± 0.19 vs 0.29 ± 0.09; p < 0.001) were observed. Higher heterogeneity of psoas FDG uptake was also documented in ALS (VC-SUV 8 ± 4%, vs 5 ± 2%, respectively, p < 0.001) and significantly predicted overall survival at Kaplan–Meier analysis. VC-SUV prognostic power was confirmed by univariate analysis, while the multivariate Cox regression model identified the spinal cord metabolic activation as the only independent prognostic biomarker.ConclusionThe present data suggest the existence of a common mechanism contributing to disease progression through the metabolic impairment of both second motor neuron and its effector.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of adult life, characterized by a progressive impairment of motor function
As previously described, FDG uptake was significantly higher in the spinal cord and lower in the brain motor cortex, in ALS compared to controls
While psoas attenuation coefficient (AAC) was similar in patients and controls, in ALS a significant reduction in psoas volume (3.6 ± 1.02 vs 4.12 ± 1.33 mL/kg; p < 0.01) and increase in psoas N-standardized uptake value (SUV) (0.45 ± 0.19 vs 0.29 ± 0.09; p < 0.001) were observed
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of adult life, characterized by a progressive impairment of motor function. Its time course is extremely variable, with time elapsing from diagnosis to death or severe inability ranging from months to years This heterogeneity prevents an accurate outcome prediction and hampers the development of new therapeutic approaches. The lack of validated biomarkers and the limited knowledge about disease mechanisms inevitably hampers the identification of target patients and limit a correct identification of treatment effects. This uncertainty raises an urgent need to develop biomarkers able to characterize the mechanisms underlying disease progression. We recently reported the potential of a computational approach in extracting spinal cord metabolism from FDG PET/CT scanning in ALS patients [1]. This approach documented a metabolic activation of this nervous site facing an opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
