Osteoarthritis (OA) affects over half the population at some point in their lives, yet treatment options and understanding of OA remain limited, in part due to limited availability of non-invasive techniques to quantify disease progression and responses to therapies. While numerous magnetic resonance imaging (MRI) methods have been proposed for imaging OA, they all have at least one major limitation, ranging from long scan times to limited specificity. We propose a new MRI technique called quantitative double-echo in steady-state (qDESS) imaging that simultaneously offers 3D morphologic and functional imaging of the entire knee, including water diffusion and rapid relaxometry measurements. This project aims to fully develop qDESS so that it may be widely used, then to assess the value of quantitative diffusion and relaxometry measures in cartilage and menisci to detect early and temporal changes.
Our specific aims are (1) to develop a robust scanning sequence and accompanying post-processing methods to obtain high-resolution 3D maps of apparent diffusion coefficient (ADC), T2 and T2* in a 10-minute scan at 3T, (2) to validate this technique with imaging of excised human samples, comparing quantitative imaging parameters with biochemical, histological and mechanical metrics in cartilage and menisci to determine sensitivity to tissue degeneration, and (3) to validate the ability of qDESS to detect changes over time in the knees of subjects at risk of developing OA following anterior cruciate ligament (ACL) tears. The innovation of this work lies in the development of a clinically feasible technique that simultaneously offers (1) morphologic images that can potentially be used for whole-knee scoring and radiologic assessment and (2) quantitative parameters in both cartilage and meniscus including volume and thickness measurements, T2 and T2* maps and ADC maps, and (3) a non-contrast-enhanced method to assess synovitis. The significance of this proposal is to offer a widely available, quantitatively validated 10-minute imaging method that makes comprehensive routine study of early osteoarthritis feasible in both research and clinical MRI exams.

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 magnetic resonance imaging approach that offers three-dimensional imaging of knee structure as well as multiple quantitative measures that can be used to assess joint health. After developing these methods we will perform studies to validate how accurately they delineate changes in tissue that are verified by mechanical testing and histology, as well as how sensitive the methods are in showing early changes over time in the knee joint in subjects at elevated risk for developing osteoarthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR063643-01A1
Application #
8577966
Study Section
Special Emphasis Panel (ZRG1-DTCS-A (81))
Program Officer
Lester, Gayle E
Project Start
2013-09-09
Project End
2018-07-31
Budget Start
2013-09-09
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$508,783
Indirect Cost
$191,784
Name
Stanford University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Jordan, C D; McWalter, E J; Monu, U D et al. (2014) Variability of CubeQuant T1?, quantitative DESS T2, and cones sodium MRI in knee cartilage. Osteoarthritis Cartilage 22:1559-67