Feasibility of ¹⁸F-FDG PET as a Noninvasive Diagnostic Tool of Muscle Denervation: A Preliminary Study

Abstract

The purpose of this study was to confirm glucose hypermetabolism in denervated muscle and investigate the feasibility of 18 F-FDG PET scanning for the detection of muscle denervation. Method: A sciatic neuropathy model in rats was created by nerve resection of the left sciatic nerve and sham operation on the other side. Eight days after denervation, small-animal PET/CT scans of the hindlimbs were acquired. Muscle denervation was confirmed by electrophysiologic and histologic study. Results: All rats showed increased 18 F-FDG uptake in the muscles of the left (denervated) lower legs. The calculated maximum lesion-to-normal counts ratio of the left lower leg anterolateral (left, 11.02 ± 2.08; right, 1.81 ± 0.40, n 5 6, P , 0.01) and posterior (left, 9.81 ± 4.58; right, 1.87 ± 0.44, n 5 6, P , 0.01) compartment were significantly increased. The electrophysiologic and histologic study verified muscle denervation. Conclusion: Glucose hypermetabolism in muscle denervation is an obvious phenomenon. 18 F-FDG PET scanning can be used to visualize muscle denervation. Needl e electromyography was the first electrophysiologic technique to evaluate peripheral neuromuscular disorder; it has been used as a main electrodiagnostic tool (1). Electromyography can detect muscle denervation resulting from various causes, such as trauma, neuropathies, and neoplasm. Although needle electromyography is currently considered as a standard test, it is an invasive and painful procedure for patients (2). Therefore, a new noninvasive diagnostic modality would be of great use. MR imaging can visualize acute and subacutely denervated muscles through high signal intensity of the muscle in fluid-sensitive MR sequences (3,4). Furthermore, MR imaging mirrors the electrophysiologic changes after denervation and also has several advantages, including the ability to detect an injured nerve itself (3,4). However, MR imaging has not been a routine study to evaluate muscle denervation and therefore cannot substitute for electromyography. Recently, increased 18 F-FDG uptake in the denervated muscle was reported incidentally (5). To our knowledge, there has not been a study that explored a direct correlation between muscle denervation and increased 18 F-FDG uptake. The purpose of this study was to confirm glucose hypermetabolism in a denervated muscle using a sciatic nerve injury rat model and to investigate the feasibility of 18 F-FDG PET scanning as a noninvasive diagnostic tool for muscle denervation. MATERIALS AND METHODS Animal ModelSix male Sprague-Dawley rats (7 wk old) were used. They were anesthetized, and the left sciatic nerve was exposed by splitting the gluteal muscles. A 10-mm nerve segment was resected just proximal to the bifurcation into the common peroneal and tibial nerves. Sham operation, exposing the sciatic nerve without resection, was performed on the right side of the rats. Additionally, one more rat was used for a tibial neuropathy model by resection of the left tibial division of the sciatic nerve around the bifurcation level wit...

Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis

“…The elevated perfusion in group HID is slight and is tended to decrease. Actually, due to huge molecular changes and apoptotic reaction, denervation is an energy-consuming process [ 27 ]. After denervation, cell death occurs with the denervated muscle fibers undergone atrophy and structural changes[ 28 ].…”

Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT

“…Moreover, the overexpression of nNOS results in secondary oxidative stress of the injured spinal cord and correlates with motoneuron apoptosis [ 11 , 12 ]. The pathological changes from the oxidative stress and apoptosis have been considered as the energy-consuming processes [ 49 ] that could be accompanied by an increase in 18 F-FDG [ 50 ]. Our data showed that the I/C ratio in the 18 F-FDG PET/CT imaging of the ipsilateral sides of the spinal cord was significantly and positively correlated with the number of nNOS positive motoneurons in the ipsilateral ventral horn, which suggests that avulsion-induced oxidative stress can be accompanied by 18 F-FDG uptake.…”

“…Combining non-invasive positron emission tomography (PET) with [ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG), a widely used PET tracer, has allowed in vivo imaging of specific biological pathways, such as increased glucose utilization in tumour cells [ 15 ], the high uptake of inflammatory cellular elements and blood supply in the clinic. In laboratory studies, 18 F-FDG micro-PET-CT (computed tomography) imaging, due to its inherent imaging characteristics, has allowed scientists to investigate whole body metabolic activity and acquire images reflecting quantitative metabolic information in regions of interests (ROIs) in small-animal models of different diseases [ 14 , 16 , 17 ]. Our recent study demonstrated that changes in 18 F-FDG micro-PET-CT images can reflect the size of ischemia and neuronal loss in the prefrontal cortex 2 weeks after cerebral ischemia/reperfusion of adult rats [ 18 ].…”

18F‐FDG uptake in denervated muscles of patients with peripheral nerve injury

“…These findings are in line with those in previous studies, although LNRmean values in this study were smaller than those in former reports. In rat models of complete sciatic nerve injury, the denervated muscles showed about 5 to 10‐times higher uptake than contralateral muscles in FDG‐PET . In a human case series of patients with spinal accessory neuropathy, their denervated trapezius muscles showed about 2 to 3‐times higher mean uptake than the unaffected side in FDG‐PET .…”

“…Behera et al reported that denervated muscles showed increased uptake in 18 F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) in an animal model . We clarified this phenomenon in a controlled animal study . Our recent study investigated its mechanisms and temporal characteristics to explore its potential as a diagnostic tool for peripheral nerve injury .…”