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Identifying Partial Muscle Denervation After Nerve Root Injury Using PET Imaging
John Nguyen
2, Bashar Alsamman
*1, Jeffrey Khong
1, Rachana Suresh
1, Samarth Krishna
1, Kiara quinn
1, Alec Chen
1, Mohammad Shahid
1, Santosh Yadav
1, Zachary Zamore
1, Fares Lebbos
1, Catherine Foss
1, William Padovano
1, Sami Tuffaha
11Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD; 2Department of General Surgery, Florida Atlantic University, Boca Raton, FL
Purpose: There is a need for improved diagnosis of partial muscle denervation for optimal management of complex peripheral nerve injuries. We identified muscle expression of glutamate carboxypeptidase II (GCPII) as a biomarker of muscle denervation and demonstrated that the FDA-approved PET radiotracer [18F]DCFPyL can identify complete muscle denervation. In this study, we examined whether [18F]DCFPyL PET can identify increasing severities of partial muscle denervation and if PET uptake changes chronically after injury.
Methods: Seventy-five female Lewis rats (6-8 weeks old) were randomized into four surgical groups: unilateral (right) selective L4 transection (n = 16), L4-L5 transection (n = 16), L4-L6 transection (n = 16), and sham surgery (n = 15). At 3 and 12 weeks post-injury, animals underwent biodistribution studies to quantify [18F]DCFPyL uptake in denervated muscles. Tissue uptake was expressed as % injected dose per gram (%ID/g). In vivo PET/MRI was performed to visualize GCPII upregulation at 3 and 12 weeks in each group (n = 2-3 per group). PET uptake was determined by drawing volumes of interest around hindlimb muscles and calculating mean radioactivity (kBq/cc) for each hindlimb. Comparisons across groups were made using one-way ANOVA with Tukey post hoc test.
Results: At both 3 and 12 weeks, increased severity of denervation resulted in increased [18F]DCFPyL uptake on biodistribution studies (Figure 1A). Complete denervation (L4-L6 transection) resulted in significantly greater uptake in the right tibialis anterior compared to sham (3 week: p < 0.001, 12 week: p < 0.001), the L4 group (p = 0.002, p < 0.001), and the L4-L5 group (p = 0.004, p < 0.001). Similar findings were identified on PET/MRI (Figure 1B), with complete denervation showing greater uptake compared to sham (p = 0.03, p = 0.001), L4 (p = 0.03, p = 0.003), and L4-L5 (p = 0.09, p = 0.003).
Conclusion: Partial muscle denervation results in graded increases in [18F]DCFPyL PET, highlighting its promise as a diagnostic tool in peripheral nerve injury.
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