Osteoarthritis (OA) is the leading cause of disability worldwide, yet its treatment options remain limited, in part due to the lack of non-invasive techniques to quantify disease progression and response to therapies. We propose to develop simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) (PET/MR) using 18F-sodium fluoride (18F-NaF) to assess subchondral bone remodeling as a marker of early OA progression and relate bone metabolism to biochemical changes in articular cartilage. This approach will provide a considerable advance for imaging of OA; including new markers of early disease and insights into the spatial and temporal progression of OA. This project aims to develop a new approach to knee imaging using PET/MR, providing fast, quantitative and registered metabolic and biochemical markers sensitive to the earliest changes in OA.
Our specific aims are (1) to develop parallel MR imaging techniques for fast and simultaneous bilateral knee MRI; (2) to create an automated attenuation correction method for flexible MRI knee coils to achieve accurate and reproducible dynamic scans of 18F-NaF PET uptake; and (3) to study the spatiotemporal relationships between bone remodeling and adjacent cartilage changes and evaluate if 18F-NaF PET can predict degenerative knee changes in subjects at risk of developing OA following anterior cruciate ligament (ACL) tears. The innovation of this work lies in the development of a novel imaging technique for studying OA, PET/MR, that offers quantitative and multimodal information sensitive to the earliest metabolic and biochemical changes in bone and cartilage. Advanced methods developed in this work will enhance fast, quantitative assessment of early disease biomarkers within each imaging modality. The significance of this work is that we will be able to sensitively and quantitatively track the earliest changes of OA, and study the spatiotemporal progression of disease. These contributions will provide new insights into OA pathogenesis, leading to new treatment targets, and ultimately therapies to arrest the onset and progression of OA.

Public Health Relevance

Although osteoarthritis affects more than half of the population during their lives and is the leading cause of disability, both treatment options and diagnostic imaging of early-stage disease are very limited. This work aims to develop a novel integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) approach, PET/MR, to assess subchondral bone remodeling as a marker of early OA progression and relate bone metabolism to biochemical changes in cartilage. These advancements will allow us to simultaneously and quantitatively track early and reversible changes in OA, providing new insights into OA pathogenesis and leading to new treatment targets and therapies to arrest the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Career Transition Award (K99)
Project #
1K99EB022634-01A1
Application #
9386607
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Atanasijevic, Tatjana
Project Start
2017-09-05
Project End
2019-06-30
Budget Start
2017-09-05
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Stanford University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Kogan, F; Fan, A P; Monu, U et al. (2018) Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI. Osteoarthritis Cartilage 26:790-796
Kogan, Feliks; Levine, Evan; Chaudhari, Akshay S et al. (2018) Simultaneous bilateral-knee MR imaging. Magn Reson Med 80:529-537
Kogan, Feliks; Broski, Stephen M; Yoon, Daehyun et al. (2018) Applications of PET-MRI in musculoskeletal disease. J Magn Reson Imaging 48:27-47