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

Abstract

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.

Keywords: PET; RMD; [18F]-FDG; glucose metabolism; myositis; osteoarthritis; rheumatoid arthritis; skeletal muscle.

Figure 1

Schematic illustration of the applied methodology. (A) Muscles of interest that were analysed in this study are important for movement and posture and include the deltoid, biceps, triceps, psoas, quadriceps, and hamstrings. (B) Fixed volume of interest (VOI) method makes use of the anatomic position that is at 50% of the plane between the proximal and distal end of a bone. The VOI is drawn in the axial plane, ensuring it does not overlap with any veins or arteries. (C) Hottest VOI method makes use of the qualitative assessment of the muscle, where the VOI is drawn at the position of the most visually apparent [¹⁸F]-FDG uptake, with the consideration that the VOI should not overlap with any veins or arteries. The image was created with BioRender. Jansen, G. (2025) https://BioRender.com/w00w379 (accessed on 8 February 2025) and PET/CT images were added separately.

Figure 2

Representative illustration of homogeneous vs. heterogeneous [¹⁸F]-FDG muscle uptake. (A) Homogeneous [¹⁸F]-FDG uptake in the deltoid muscle is represented: a homogeneous red color can be observed. (B) Heterogeneous [¹⁸F]-FDG uptake in the quadriceps and hamstrings: multifocal red patches can be observed. Muscles are indicated by yellow dotted lines. Tracer uptake is represented in red. Scaling of [¹⁸F]-FDG uptake intensity is indicated by the scale-bar on the right: SUV is set between 0.4 and 3.5 for optimal visualization of tracer uptake.

Figure 3

Investigation of the difference in intramuscular uptake of [¹⁸F]-FDG between the fixed and the hotspot methods in the quadriceps muscle across all RMDs and controls. (A) Visualization of the Spearman correlation between the fixed VOI and hotspot methods (R² = 0.745). (B) Bland–Altman plot of the differences between fixed and hotspot VOI methods vs. the mean of the two methods.

Figure 4

Intramuscular uptake of [¹⁸F]-FDG as assessed with the hotspot VOI in the psoas, hamstrings, and quadriceps of patients with RA, OA, and IIM in comparison to the controls. Quantification of [¹⁸F]-FDG uptake is represented by SUV_peak in (A) the psoas, (B) the hamstrings, and (C) the quadriceps for (from left to right) control persons, patients with RA, OA, and IIM. Quantitative data are presented as mean ± SEM, N = 7–11/group, * p < 0.05, ** p < 0.01, Kruskal–Wallis test with multiple comparison of the mean rank differences.