Neurovascular, Muscle, and Skin Changes on [18F]FDG PET/MRI in Complex Regional Pain Syndrome of the Foot: A Prospective Clinical Study

Abstract

Objective: The goal of this study is to demonstrate the feasibility of simultaneous [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) for noninvasive visualization of muscular, neurovascular, and skin changes secondary to complex regional pain syndrome (CRPS).

Subjects: Seven adult patients with CRPS of the foot and seven healthy adult controls participated in our [18F]FDG PET/MRI study.

Methods: All participants received whole-body PET/MRI scans 1 hour after the injection of 370MBq [18F]FDG. Resulting PET/MRI images were reviewed by two radiologists. Metabolic and anatomic abnormalities identified, were grouped into muscular, neurovascular, and skin lesions. The [18F]FDG uptake of each lesion was compared with that of corresponding areas in controls using a Mann-Whitney U-test.

Results: On PET images, muscular abnormalities were found in five patients, neurovascular abnormalities in four patients, and skin abnormalities in two patients. However, on MRI images, no muscular abnormalities were detected. Neurovascular abnormalities and skin abnormalities in the affected limb were identified on MRI in one and two patients, respectively. The difference in [18F]FDG uptake between the patients and the controls was significant in muscle (P = .018) and neurovascular bundle (P = .0005).

Conclusions: The increased uptake of [18F]FDG in the symptomatic areas likely reflects the increased metabolism due to the inflammatory response causing pain. Therefore, our approach combining metabolic [18F]FDG PET and anatomic MR imaging may offer noninvasive monitoring of the distribution and progression of inflammatory changes associated with CRPS.

Trial registration: ClinicalTrials.gov NCT03195270.

Keywords: Complex Regional Pain Syndrome; Muscle; Nerve; Skin; [18F]FDG PET/MRI.

Figure 1.

Locally high [¹⁸F]FDG uptake on foot muscles at the site of pain symptom from two patients in comparison with no abnormalities of a healthy control subject. High [¹⁸F]FDG uptake was identified (red arrows) on the left extensor digitorum brevis muscle (A: PET only, D: PET/MRI coregistered) from Patient 7 and left flexor digitorum brevis muscle (B: PET only, E: PET/MRI coregistered) from Patient 2. No structural damage or abnormal signal intensity was observed on the MRI image. The PET-only image (C) and PET/MRI coregistered image (F) at a similar slice location from a control subject do not show focally increased [¹⁸F]FDG uptake or structural abnormalities. The unit of PET signal on the images is SUV. The same color scale (0–1.7) was used for all subfigures for PET. MRI = magnetic resonance imaging; PET = positron emission tomography.

Figure 2.

Increased [¹⁸F]FDG uptake on neurovascular bundles at the site of pain symptom from a patient in comparison with no abnormalities from a healthy control. Locally increased [¹⁸F]FDG uptake was detected on the tibial neurovascular bundle passing through the scar tissue at the ankle of Patient 4 and marked by the yellow arrow (A: PET only, C: PET/MRI coregistered). Again, the PET-only image (B) and PET/MRI coregistered image (D) at a similar slice location from a healthy control subject shows no abnormalities. The unit of PET signal on the images is SUV. The same color scale (0–1.7) was used for all subfigures for PET. MRI = magnetic resonance imaging; PET = positron emission tomography.

Figure 3.

Globally Increased [¹⁸F]FDG uptake on neurovascular bundles along the site of pain symptom on maximum intensity projection PET images. Healthy controls did not present noticeably high [¹⁸F]FDG uptake on neurovascular bundles compared to the background tissues as shown in a representative control (A: PET only). However, a significantly increased [¹⁸F]FDG uptake was found bilaterally on multiple neurovascular bundles from Patient 3 with bilateral foot and leg pain (B: PET only, white arrows). The unit of PET signal on the images is SUV. The same color scale (0–1.7) was used for all subfigures. MRI = magnetic resonance imaging; PET = positron emission tomography.

Figure 4.

[¹⁸F]FDG PET and MRI abnormalities of skin and subcutaneous tissue of the symptomatic lower leg from Patient 5 (A: PET only, C: PET/MRI coregistered) in comparison with no abnormalities on the PET-only image (B) and PET/MRI coregistered image (D) from a healthy control subject. Increased uptake of [¹⁸F]FDG was identified on PET (white arrows) where edematous skin and subcutaneous tissue thickening was detected on MRI. The unit of PET signal on the images is SUV. The same color scale (0–1.7) was used for all subfigures for PET. MRI = magnetic resonance imaging; PET = positron emission tomography.

Figure 5.

Mean and standard deviation of [¹⁸F]FDG SUV_max in muscle, neurovascular bundle, and skin lesions of CRPS patients and corresponding tissues of healthy controls. SUV_max in the lesions in muscle and nerve tissues show statistically significant differences than controls (P < .05). CRPS = complex regional pain syndrome.