To introduce early clinical results with an [18F] FDG PET/MRI method for advanced diagnosis of chronic painPain, whether it is back pain, arthritic, headache, etc., is now the most common reason to seek medical attention worldwide, surpassing the number of visits for heart disease, cancer and diabetes combined¹. The chronic pain sufferer, however, is currently faced with a lack of objective tools to identify the source of their pain. In chronic pain, neural tissues as well as any associated inflamed tissues, are hypermetabolic and, therefore, glucose avid- a phenomenon that has been previously demonstrated in pre-clinical models of neuropathic pain². Accordingly, the overarching goal of this work is to develop a clinical [18F]FDG PET/MRI method to more accurately localize sites of increased tissue inflammation as it relates to sources of pain. The aims are to 1) determine whether imaging findings correlate with location of pain symptomology (radiologist unblinded to patient exam or history), 2) determine whether location of symptoms can be determined by MR imaging findings alone or PET/MRI imaging findings (radiologist blind to patient physical exam and history) and 3) to determine whether the imaging results affect current management decisions.Patients suffering from unilateral chronic lower extremity neuropathic pain, specifically complex regional pain syndrome (CRPS) and sciatica, have been referred directly from pain physician specialists. Fourteen chronic pain patients (10 complex regional pain syndrome and 4 chronic sciatica) have been imaged with a GE SIGNA PET/MRI system (time-of-flight PET; 3.0T bore; 4-8 min/bed position) from mid thorax through the feet. All patients underwent PET/MR imaging one hour after a single 10 mCi injection of [18F]FDG. MRI sequences obtained include a coronal DESS, coronal PSIF (isotropic), axial LAVA FLEX (with water/fat separation) and axial T2W FSE with fat-saturation. Two radiologists evaluated PET/MR images (one blinded and the other unblinded to patient exam and history). Using image analysis methods (standard uptake value (SUV) measurements and target-to-background measurements) and image analysis software (OsiriX v.6.0 64-bit), the radiologist unblinded to the patient exam and history determined if increased [18F]FDG uptake occurred in the site of symptoms as well as in other areas of the body. The radiologist blinded to the patient history and exam had to name the side of the symptoms and location. Imaging results were discussed with referring physician, who then determined whether a change in the management plan would follow (i.e., no change, mild change (additional diagnostic test ordered), significant change (minimally invasive or surgical procedure performed).

ROI analysis showed focal increased [18F]FDG uptake in affected nerves and muscle (approx 2-4 times more) over background tissue in various regions of the body in 13 of 14 patients at the site of greatest pain symptoms and other areas of the body (SUVmax of Target 0.9-4.2 vs. Background 0.2-1.2).

Figure 1 is an example of a patient with complex regional pain syndrome (CRPS) with right dorsal ankle/foot pain. Increased FDG uptake was identified near the right plantaris muscle, the deep peroneal nerve, and the deep fibular nerve, correlating well with the locations of patient’s symptoms. Figure 2 is an example of a presumed scar neuroma in the left calf. Increased [18F] FDG uptake was observed near the site of pain, but no abnormality was found in MRI. Figure 3 is an example of a patient with right-sided chronic sciatica, where MRI showed low signal intensity and PET showed increased FDG uptake on herniated disc material impinging nerve roots.

The radiologist blinded to the patient history/exam was able to correctly identify side/location of the symptoms in 6 of 14 (MRI data only) and 12 out of 14 patients (PET/MRI data) (Table 1). Imaging results were reviewed with the referring physician, who then determined whether a modification in the management plan was needed as follows: 2/14 no change, 4/14 mild modification (e.g., additional diagnostic test ordered) and 8/14 significant modification (e.g., new invasive procedure or new medical therapy suggested or ordered).

Our early experience suggests that [18F]FDG PET/MRI can identify hypermetabolic or inflammatory abnormalities in patients suffering from neuropathic pain. We have seen new plans implemented in 12 out of 14 patients, which were not anticipated by the referring physician. While initial results show some promise, the imaging data will have to be carefully scrutinized for non-specific uptake of [18F]FDG which can be observed in non-painful muscle recruitment, age-related arthritic changes and atherosclerotic vascular tissue. As we recruit more patients for the study, we will gain more insight into the strengths and limitations of this approach in helping people with chronic neuropathic pain.