Over 50 million Americans are affected by Osteoarthritis (OA), which leads to a compromised quality of life and places an enormous burden on the healthcare system. Current clinically available treatment methods mainly offer symptomatic relief but are unable to alter its natural course. Since there is no cure for the disease, early detection and appropriate therapeutic intervention potentially may stop the disease progression. Current diagnostic methods include radiography, arthroscopy and magnetic resonance imaging (MRI). Radiography can only detect gross tissue losses and hence useful only to detect late macroscopic cartilage losses. Arthroscopy can detect earliest changes in cartilage, but it is invasive surgical procedure and not conducive for longitudinal monitoring of the disease. Although, MRI can detect gross focal defects of cartilage the conventional MRI has proven inconclusive for detecting early degenerative changes of cartilage such as chondromalacia. Recently we demonstrated, in ex vivo studies, that Tlp imaging of water in cartilage can track early biochemical changes in OA. In this proposal, we will develop and optimize this method for quantifying early degenerative changes in humans in vivo. We will first optimize this method for human applications in terms of sequence parameters, radiofrequency field inhomogeneities and time efficiency. This will be followed by the determination of accuracy and precision of Tlp relaxation mapping and dispersion on human subjects in vivo. We will then measure the age dependent variations of cartilage Tlp on healthy volunteers with varying age groups. In the fourth aim of the proposal, Tlp relaxation mapping will be performed on human subjects who have been diagnosed with early OA and correlate the Tlp results with size and location of arthroscopically scored lesions of cartilage. Finally, Tlp measurement on a group of early OA subjects will be performed in a temporal fashion, which will enable us to determine the efficacy of the method in longitudinal monitoring of the disease progression. Once accomplished, results from this project will enable one to use the relaxation rate as a quantitative, surrogate marker for early changes that occur before the onset of morphological changes in OA. A major advantage of this approach is that it does not require any additional hardware modification or administration of exogenous contrast agent. Successful completion of the proposed work, has the potential to profoundly affect our ability to study OA process and to diagnose and monitor the disease in a quantitative fashion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR045404-08
Application #
7637767
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Lester, Gayle E
Project Start
1999-09-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2011-06-30
Support Year
8
Fiscal Year
2009
Total Cost
$321,974
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Singh, Anup; Cai, Kejia; Haris, Mohammad et al. (2013) On B1 inhomogeneity correction of in vivo human brain glutamate chemical exchange saturation transfer contrast at 7T. Magn Reson Med 69:818-24
Singh, Anup; Haris, Mohammad; Cai, Kejia et al. (2012) Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magn Reson Med 68:588-94
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Witschey, Walter R T; Borthakur, Arijitt; Fenty, Matt et al. (2010) T1rho MRI quantification of arthroscopically confirmed cartilage degeneration. Magn Reson Med 63:1376-82
Wang, Chenyang; Witschey, Walter; Elliott, Mark A et al. (2010) Measurement of intervertebral disc pressure with T 1? MRI. Magn Reson Med 64:1721-7
Witschey, Walter R T; Pilla, James J; Ferrari, Giovanni et al. (2010) Rotating frame spin lattice relaxation in a swine model of chronic, left ventricular myocardial infarction. Magn Reson Med 64:1453-60

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