[18F]FDG PET/MRI Of Patients With Chronic Pain Alters Management: Early Experience. Deepak Behera1, DaeHyun Yoon1, Dawn Holley1, Ma Agnes Martinez Ith2, Ian Carroll3, Matthew Smuck2, Brian Hargreaves1 and Sandip Biswal1. 1
Department of Radiology, Stanford University School of Medicine; 2Department of Orthopaedics, Stanford University SOM; 3Department of Anesthesia, Stanford University SOM. Aims Pain, whether it is back pain, arthritis, headache, etc., is now the most common reason to seek medical attention worldwide, surpassing the number of visits for heart disease, cancer and diabetes combined. The chronic pain sufferer, however, is currently faced with a lack of objective tools to identify the source of their pain. The goal of the effort described here is to develop clinical imaging methods to more accurately localize chronic pain generators/drivers so that we may objectively identify and more intelligently act upon the cause in a pain sufferer. In chronic pain, continuously or spontaneously firing neurons, as well as any associated inflamed tissues, are hypermetabolic and, therefore, glucose avid. This phenomenon can be exploited to visualize increased neural metabolism, and, therefore, increased nociceptive activity in the nervous system using [18F]FDG PET/MRI. In a rat model of neuropathic pain, Behera et al. (J Nuc Med (2011) 52(8):1308-­‐12) could localize increased FDG uptake in injured nerves using PET/MRI, which, in turn, correlated significantly with behavioral measurements of allodynia in the affected paw. The overarching goal of this work is to develop clinical [18F]FDG PET/MRI methods to more accurately localize sites of increased neuronal and muscular inflammation as it relates to neurogenic sources of pain. Ultimately, we aim to improve outcomes of chronic pain sufferers by facilitating personalized, image-­‐informed treatments of peripheral pain generators. 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 imaging findings alone (radiologist blind to patient physical exam and history) and 3) to determine whether the imaging results affect current management decisions. Methods and materials Patients suffering from chronic lower extremity neuropathic pain have been referred directly from pain physician specialists. Prior to patient recruitment, the management plan was reviewed via chart review and discussion with the referring physician. To date, 6 chronic pain patients (4 complex regional pain syndrome, 1 chronic sciatica and 1 neuropathic pain) have been imaged with a PET/MRI system (time-­‐of-­‐flight PET; 3.0T bore) from mid thorax through the feet. All patients underwent PET/MR imaging one hour after a single-­‐
injection of [18F]FDG at approximately 4-­‐8 min/bed position. MRI sequences obtained in each bed position include a coronal DESS, coronal PSIF (isotropic), axial LAVA FLEX (with water and fat separated). 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 32-­‐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 blind 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). Results 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 5 of 6 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 CRPS with dorsal ankle/foot pain, and Figure 2 is an example of a patient with chronic sciatica. The radiologist blind to the patient history/exam was able to correctly identify side/location of the symptoms in 5 out of 6 patients. Imaging results were reviewed with the referring physician, who then determined whether a modification in the management plan was needed. The modifications to the plan were as follows: 1/6 no change, 2/6 mild modification (e.g., additional diagnostic test ordered) and 3/6 significant modification (e.g., new invasive procedure or new medical therapy ordered). Discussion – Conclusion Our early experience thus far suggest that [18F]FDG PET/MRI can identify hypermetabolic or inflammatory abnormalities in patients suffering from Figure 1: Axial [18F]FDG PET/MRI of a patient with complex regional pain syndrome of the neuropathic pain. We can use this right foot shows increased [18F]FDG uptake (red arrows) in the vicinity of the right deep information to determine how to approach fibular nerve (green arrows) and surrounding soft tissues in the dorsal part of the ankle/proximal foot. the chronic pain patient and intervene in a manner that potentially improves outcome. The ongoing study will determine whether these interventions affect patient outcomes in terms of pain scores, disability indices and other outcome measures. In the few patients performed to date, we have seen new plans implemented in 5 out of 6 patients, which were not anticipated by the referring physician. Certainly, while initial results show some promise, the imaging data will have to be carefully scrutinized for non-­‐specific uptake of [18F]FDG since uptake can be affected by non-­‐painful muscle recruitment, age-­‐related arthritic changes and 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. Figure 2: Coronal MRI, PET and fused PET/MR image taken of a patient suffering from chronic right-­‐sided chronic sciatica. The MR image is a coronal DESS through the lumbosacral spine through the neuroforamina of L5-­‐S1. The white arrow points to the right L5-­‐S1 neuroforamina. Coronal PET image shows increased FDG uptake at the lumbosacral junction in the right L5-­‐S1 neuroforamina (white arrow) as confirmed by the fused PET/MR image. The patient’s symptoms were confirmed to involve the right back and leg. Ongoing work will determine if PET/MRI is a more accurate predictor of pain generators over conventional methods.