Interactions between all the major joint tissues, including the articular cartilage, meniscus, and trabecular bone have been implicated in osteoarthritis (OA). Magnetic resonance (MR) images have been used to quantify the cartilage morphology, volume and thickness, relaxation times T2 and T1?. During the prior funding period, the relationship between cartilage T2 and T1? (mean and spatial heterogeneity), radiographic Kellgren-Lawrence (KL) score, the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), changes in cartilage volume, thickness, trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), fat/water ratios in bone marrow edema like lesions (BMEL) was established. Meniscus and cartilage have similar biochemical constituents, load-dissipating function, and undergo repetitive loading, thus, T2 and T1? methods may also be extended to studying meniscus. Differences in loaded and unloaded T2 and T1? of cartilage and meniscus may reflect biochemical composition and levels of degeneration may potentially be a metric for predicting the progression of OA. This renewal will add to the field of research by extending the quantitative approach of the original proposal to the meniscus, an important tissue in OA, acquire additional years of follow-up for cartilage and bone measures, and examine changes in the soft tissues with loading, where loading at 50% body weight will be accomplished using a device built in-house.
Specific Aim 1 : To quantify both cross-sectionally and longitudinally (annual over 3 years), differences in regional variations and spatial heterogeneity of T2 and T1? maps of the meniscus in controls and subjects with OA. To establish the correlation of the meniscus metrics with metrics from surrounding and overlying cartilage volume and thickness, cartilage T2 and T1? maps, trabecular bone morphology, morphological grades (WORMS), and functional scores (WOMAC).
Specific Aim 2 : To compare baseline and longitudinal differences in unloaded and loaded cartilage and meniscus T2 and T1? (loaded T2-unloaded T2 =?T2 and similarly ?T1A) in controls and OA subjects, and whether baseline ?T2 and ?T1A predict disease progression.

Public Health Relevance

This study will develop non invasive biomarkers for cartilage and meniscus degeneration in the knee. We will also examine differences in these tissues with loading. This will help individuals who have or are at 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 #
5R01AR046905-13
Application #
8471059
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
Project Start
1999-09-17
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
13
Fiscal Year
2013
Total Cost
$586,557
Indirect Cost
$192,705
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Calixto, Nathaniel E; Kumar, Deepak; Subburaj, Karupppasamy et al. (2016) Zonal differences in meniscus MR relaxation times in response to in vivo static loading in knee osteoarthritis. J Orthop Res 34:249-61
Pedoia, Valentina; Li, Xiaojuan; Su, Favian et al. (2016) Fully automatic analysis of the knee articular cartilage T1ρ relaxation time using voxel-based relaxometry. J Magn Reson Imaging 43:970-80
Teng, H-L; Calixto, N E; MacLeod, T D et al. (2016) Associations between patellofemoral joint cartilage T1ρ and T2 and knee flexion moment and impulse during gait in individuals with and without patellofemoral joint osteoarthritis. Osteoarthritis Cartilage 24:1554-64
Guha, Aditi; Wyatt, Cory; Karampinos, Dimitrios C et al. (2015) Spatial variations in magnetic resonance-based diffusion of articular cartilage in knee osteoarthritis. Magn Reson Imaging 33:1051-8
MacLeod, Toran D; Subburaj, Karupppasamy; Wu, Samuel et al. (2015) Magnetic resonance analysis of loaded meniscus deformation: a novel technique comparing participants with and without radiographic knee osteoarthritis. Skeletal Radiol 44:125-35
Teng, Hsiang-Ling; MacLeod, Toran D; Link, Thomas M et al. (2015) Higher Knee Flexion Moment During the Second Half of the Stance Phase of Gait Is Associated With the Progression of Osteoarthritis of the Patellofemoral Joint on Magnetic Resonance Imaging. J Orthop Sports Phys Ther 45:656-64
Kumar, Deepak; Souza, Richard B; Subburaj, Karupppasamy et al. (2015) Are There Sex Differences in Knee Cartilage Composition and Walking Mechanics in Healthy and Osteoarthritis Populations? Clin Orthop Relat Res 473:2548-58
Subburaj, Karupppasamy; Souza, Richard B; Wyman, Bradley T et al. (2015) Changes in MR relaxation times of the meniscus with acute loading: An in vivo pilot study in knee osteoarthritis. J Magn Reson Imaging 41:536-43
Teng, Hsiang-Ling; MacLeod, Toran D; Kumar, Deepak et al. (2015) Individuals with isolated patellofemoral joint osteoarthritis exhibit higher mechanical loading at the knee during the second half of the stance phase. Clin Biomech (Bristol, Avon) 30:383-90
Kumar, D; Karampinos, D C; MacLeod, T D et al. (2014) Quadriceps intramuscular fat fraction rather than muscle size is associated with knee osteoarthritis. Osteoarthritis Cartilage 22:226-34

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