Candidate and Career Development Plan. The candidate is well trained in bioengineering with an emphasis on quantitative Magnetic Resonance Imaging (MRI). Her long-term scientific goal is to improve the understanding, detection, and treatment of serious diseases through non-invasive imaging techniques, and to ultimately improve the quality of health care. In the short term, with this award, the candidate aims to obtain the necessary training in order to become an independent biomedical researcher;specifically, to be able to initiate and conduct her own research program in quantitative MRI for osteoarthritis and knee injuries. The candidate and her mentor have assembled a team of independent investigators in both basic science and clinical related fields to help her achieve this goal. The proposed career development plan includes 1) protected at least 75% research time, 2) a systematic training in biology/pathology and clinical aspects of musculoskeletal diseases by attending courses, journal clubs, seminars, scientific meetings, and regular nteractions with co-investigators;3) a research plan for acquiring new research skills and expertise. Research. Osteoarthritis (OA) is the most common joint disease characterized by cartilage degeneration. Non-invasive early detection of cartilage degeneration in OA is of increasing clinical importance. Current imaging techniques are limited to providing primarily morphologic changes of cartilage that tend to occur at late stages of OA. We propose to develop advanced MRI techniques at a high field strength (3 Tesla) for early detection of cartilage degeneration by probing changes in collagen-proteoglycan (PG) matrix. Our preliminary data have shown MR T1p relaxation time as a promising candidate for this purpose. The objective of the proposed project is to 1) further develop in vivo Tip mapping techniques on a 3T scanner, 2) to establish its relationship with collagen-PG matrix using cartilage specimens from OA patients who undergo total knee arthroplasty;and 3) to explore its clinical significance by monitoring cartilage damage longitudinally in knees with anterior cruciate ligament (ACL) tear that are at high risk for posttraumatic OA. Tip values will also be compared with TZrelaxation time and post-contrast TI relaxation time with delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC). The driving hypothesis is that in vivo measurement of these relaxation times can detect early cartilage degeneration before morphologica changes are observed. In the future, these techniques may permit a critical evaluation of new surgical and pharmacological techniques to treat damaged cartilage. The results of this study are also anticipated to provide direction and tools for better management for ACL ruptures and potentially other knee injuries. In summary, the proposal addresses a significant issue in musculoskeletal diseases, and will serve wel as a training vehicle to establish research independency of the candidate.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Mentored Quantitative Research Career Development Award (K25)
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Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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Lester, Gayle E
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Tufts, Lauren S; Shet, Keerthi; Liang, Fei et al. (2016) Quantification of bone marrow water and lipid composition in anterior cruciate ligament-injured and osteoarthritic knees using three-dimensional magnetic resonance spectroscopic imaging. Magn Reson Imaging 34:632-7
Theologis, Alexander A; Haughom, Bryan; Liang, Fei et al. (2014) Comparison of T1rho relaxation times between ACL-reconstructed knees and contralateral uninjured knees. Knee Surg Sports Traumatol Arthrosc 22:298-307
Li, Xiaojuan; Wyatt, Cory; Rivoire, Julien et al. (2014) Simultaneous acquisition of T1? and T2 quantification in knee cartilage: repeatability and diurnal variation. J Magn Reson Imaging 39:1287-93
Gupta, Riti; Virayavanich, Warapat; Kuo, Daniel et al. (2014) MR T(1)? quantification of cartilage focal lesions in acutely injured knees: correlation with arthroscopic evaluation. Magn Reson Imaging 32:1290-6
Kumar, Deepak; Kothari, Abbas; Souza, Richard B et al. (2014) Frontal plane knee mechanics and medial cartilage MR relaxation times in individuals with ACL reconstruction: A pilot study. Knee 21:881-5
Li, Xiaojuan; Majumdar, Sharmila (2013) Quantitative MRI of articular cartilage and its clinical applications. J Magn Reson Imaging 38:991-1008
Su, F; Hilton, J F; Nardo, L et al. (2013) Cartilage morphology and T1? and T2 quantification in ACL-reconstructed knees: a 2-year follow-up. Osteoarthritis Cartilage 21:1058-67
Jobke, Bjoern; Bolbos, Radu; Saadat, Ehsan et al. (2013) Mechanism of disease in early osteoarthritis: application of modern MR imaging techniques -- a technical report. Magn Reson Imaging 31:156-61
Jungmann, Pia M; Li, Xiaojuan; Nardo, Lorenzo et al. (2012) Do cartilage repair procedures prevent degenerative meniscus changes?: longitudinal t1ýý and morphological evaluation with 3.0-T MRI. Am J Sports Med 40:2700-8
Kothari, Abbas; Haughom, Bryan; Subburaj, Karupppasamy et al. (2012) Evaluating rotational kinematics of the knee in ACL reconstructed patients using 3.0 Tesla magnetic resonance imaging. Knee 19:648-51

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