18F-Fluoride PET-MR Imaging of Metabolic Bone Activity in Knee Osteoarthritis

318 Objectives Osteoarthritis (OA) is a chronic, degenerative disease that affects all joint tissues and causes pain, stiffness and loss of mobility in 27 million Americans. Bone remodeling is an important aspect of OA progression; however, the role of bony metabolic activity is unclear. This study investigates the use of 18F-Fluoride PET-MR imaging to detect and characterize osseous metabolic abnormalities in patients with knee OA and correlate bony features of OA observed on MRI with 18F-Fluoride uptake on PET. Methods Both knees of 10 subjects with idiopathic or traumatic radiographic knee OA were imaged on a 3T PET-MR hybrid system following injection of 2.5-5 mCi of 18F-Fluoride. Two experienced MSK radiologists identified the following bony features of OA on MR images: Bone marrow lesions (BMLs) and osteophytes (according to MRI OA Knee Score (MOAKS)) and subchondral sclerosis. The maximum pixel standardized uptake values (SUVmax) from volumes of interest (VOI) on PET images corresponding to bone pathology identified on MRI were compared between different bony features as well as between individual pathology MOAKS grade. VOIs with SUV greater than 5 times the mean background bone SUV were identified (VOIhigh) on PET SUV maps. A Wilcoxon signed-rank test was used to compare SUVmax from different bone pathology to each other. Additionally, SUVmax from VOIhigh that didn’t correlate with MRI findings were identified and were compared to MR findings of bone pathology. Results Figure 1 displays example PET and MRI images of three patients with traumatic OA showing correlation between BMLs, osteophytes, and sclerosis on MRI with high 18F-Fluoride uptake on PET. BMLs observed on MRI consistently correlated with 18F-Fluoride PET VOIhigh (25 of 26). Furthermore, SUVmax associated with BMLs was significantly higher than that of osteophytes or sclerosis (p<0.001) (fig. 2a). This suggests that BMLs are significantly more metabolically active than osteophytes and sclerosis. Additionally, significant correlations were observed between SUVmax and BML grade based off MOAKS scoring (p<0.05) (fig. 2b). Association between 18F-Fluoride VOIhigh and MRI findings of osteophytes (49 of 70) and sclerosis (6 of 10) was less consistent. However, similar to BMLs, there were significant correlations between SUVmax and osteophyte grade (p<0.05) (fig. 2c). The sensitivity of 18F-Fluoride PET-MR to bone remodeling may help us to better understand and characterize these lesions in subchondral bone. Furthermore, many of the small osteophytes used to identify early signs of OA on radiographs did not show focal uptake of 18F-Fluoride. A lack of metabolic activity may signal that certain pathology play a reduced role in OA progression. Of significant interest, high 18F-Fluoride uptake in subchondral bone did not always correspond to structural damage detected on MRI (23 of 103 areas of VOIhigh) (fig. 1c). Subchondral bone is a region that is associated with the development of pain as well as cartilage degeneration, and 18F-Fluoride PET-MR data suggests that metabolic abnormalities in the bone may occur prior to structural changes are seen on MRI. Additionally, in subjects with unilateral ligament injuries, 1 to 3 years post injury, more regions of high 18F-Fluoride uptake were observed in the injured knee (48 VOIhigh) compared to the contralateral knee (4 VOIhigh) (fig. 3). As patients with ACL injuries have been shown to develop macromolecular changes in cartilage as early as 1-year post injury, this demonstrates that PET-MR may be an ideal tool to simultaneously examine longitudinal changes in bone and articular cartilage. Conclusions This work demonstrates the potential of 18F-Fluoride PET-MR to evaluate metabolic bone activity in subchondral bone. This will allow for a better understanding of the role of bony changes in OA pathogenesis. Additionally, 18F-Fluoride PET-MR may detect knee abnormalities unseen on MRI alone and is a promising tool for detection of early metabolic changes in OA. $$graphic_2D6559D4-C1A3-484B-B17C-0EBFF976C734$$ $$graphic_CC1B07C3-9A5E-48C8-BE76-7CEDCEFDD6C3$$ $$graphic_9ED601E5-CBC6-45EF-9B41-8CEF513D9253$$