Methodology Development for Investigating Pathophysiological [¹⁸F]-FDG Muscle Uptake in Patients with Rheumatic...

Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([¹⁸F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [¹⁸F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [¹⁸F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [¹⁸F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [¹⁸F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [¹⁸F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [¹⁸F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland-Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [¹⁸F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [¹⁸F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [¹⁸F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUV_peak are recommended for quantitative assessment. High [¹⁸F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles.