PET/MR imaging of sigma-1 receptor pinpoints previously undetectable abnormalities in chronic pelvic pain

180 Objectives: Chronic pelvic pain is a common, debilitating condition among women, affecting about 15% of those in westernized countries1, 2. Unfortunately, current diagnostic methods leave half of chronic pelvic pain cases without a clear diagnosis2, 3. For example, up to 46% of chronic pelvic pain patients presents no findings on MRI, the current imaging modality of choice, despite a gynecological structural cause on laparoscopy4. In this abstract, we report initial results from a novel PET/MRI approach for improved detection of chronic pelvic pain generators by localizing the activation of sigma-1 receptor (S1R), a molecular chaperone deeply involved with nociceptive processes. Methods: Five chronic pelvic pain patients (ages 25-69) with a minimum pain level 4 on a 1-10 Comparative Pain Scale participated in our PET/MRI study. Prior to imaging, all patients signed an informed consent form approved by the institutional review board. A whole-body PET/MRI scan was performed 30 minutes after the 10-mCi injection of highly S1R-specific radioligand (S1RR), also known as 18F-FTC-1465. In the bed position covering the pelvis, 3D axial LAVA-FLEX, 2D axial T2w-FSE-FLEX, multi-planar T1w FSE, T2w 2D FSE, and 3D axial DESS MRI sequences were simultaneously acquired with a time-of-flight PET scan. Two radiologists reviewed the MR images first for painful pathologies and then PET images to determine abnormal S1RR uptake in comparison with normal controls (n=5, ages 28-49). Finally, the co-registered PET/MRI images were reviewed using the location and laterality of pain at the time of imaging. The pelvic region was segmented in 5 tissue types (uterus, vagina, pelvic bowel, gluteus maximus, liver) and the standardized uptake value (SUV) of 18F-FTC-146 was measured for each segmented region using Horos software (https://horosproject.org/). The image findings were later matched to the findings from the follow up treatments for validation. Results: All five patients showed abnormally increased uptake of S1RR compared to normal uptake from controls as summarized in Table 1. In contrast, only 3 out of 5 patients showed MR abnormalities that were contributory to the symptoms of pelvic pain. Figure 1 compares an example case of abnormal S1RR uptake in the uterus (SUVmax = 9.5), which is markedly higher than the healthy control case (mean SUVmax = 3.9). This patient’s pain was relieved after hysterectomy with a pathological diagnosis of infarcted fibroid and endometriosis. Figure 2 demonstrates a case of abnormally increased S1RR uptake in the vagina (SUVmax = 5.5) in comparison with an example case from healthy controls (mean SUVmax = 3.0). The patient’s pain improved after a diagnostic laparoscopy, cystoscopy, and vaginal trigger point injection, and the surgical sample confirmed endometriosis on pathology. Figure 3 depicts a patient with increased uptake of a large area within a large area of the bowel (SUVmax = 5.8) compared to healthy controls (mean SUVmax = 2.4). The patient 5, who had extensive endometriosis and adhesive disease, also showed a similar bowel uptake pattern without MR abnormalities. This may suggest our approach could be useful for detecting these conditions, which are quite difficult to identify on MR imaging alone. Conclusions: In this preliminary study, our S1R PET/MRI method showed previously undetected abnormalities in chronic pelvic pain patients, yielding stronger evidence to support treatment decisions. S1R PET images revealed abnormalities in conditions difficult to identify by MR imaging alone, including adhesive disease or late stage endometriosis. In a subset of patients, our results suggest the presence of abnormally increased expression of S1R in tissues without any noticeable abnormalities on MRI. Therefore, S1R PET combined with high-resolution structural MRI can be a promising method to uncover a wide variety of painful pathologies in chronic pelvic pain. Acknowledgement: GE Healthcare, NIH P41 EB015891.