The Stanford Knee Osteoarthritis PET/MRI Evaluation (SKOPE) Study Protocol

Purpose: The primary objective of the Stanford Knee Osteoarthritis PET/MRI Evaluation (SKOPE) study is to develop and evaluate a multimodal, dynamic [18F]NaF PET-MRI framework for characterizing whole-joint physiology and its relationship to osteoarthritis (OA) risk, pain, and disease progression. Specifically, we aim to integrate dynamic PET with quantitative and anatomical MRI, to characterize structural, compositional, and metabolic features across the knee and surrounding musculoskeletal system, evaluate acute tissue responses to exercise, and identify imaging biomarkers associated with OA risk, pain, and disease progression. Methods: The SKOPE study includes multimodal PET-MRI of the knee and surrounding musculoskeletal tissues, with imaging of the knee, tibia, ankle, thigh, hip, pelvis, and lumbosacral spine. Dynamic [18F]NaF PET is combined with conventional anatomical MRI and quantitative MRI techniques, including quantitative double-echo steady-state (qDESS) T2 mapping of cartilage, Dixon fat-fraction imaging, ultrashort echo time (UTE) T2* mapping of short-T2 tissues, UTE imaging of tibial bone, and zero echo time (ZTE) imaging for bone morphology and pseudo-CT generation. Additional MRI sequences characterize muscle composition, bone and joint anatomy, intervertebral discs, and regional vascular anatomy. Selected scans are acquired before and after a standardized exercise protocol to assess the acute physiological response of the joint. Automated segmentation is used to generate subject-specific masks of muscles, bones, vertebrae, and intervertebral discs. A subset of the MRI protocol is repeated at 1- and 2-year follow-up to assess longitudinal changes. Expected Impact: By combining dynamic bone metabolic imaging with quantitative measures of cartilage, menisci, muscle, bone, fat, vascular structures, and the spine and hip, the SKOPE protocol provides a whole-joint and multijoint framework for studying the structural, metabolic, and physiological processes associated with OA and pain. Exercise and longitudinal imaging further enable assessment of acute tissue responses and changes over time, supporting the development of quantitative imaging biomarkers for OA risk, pain, and disease progression.