Magnetic resonance imaging (MRI) maintains its position as the gold standard for visualization of cartilagedefects and overall assessment of cartilage morphology. However, the earliest markers of cartilagedegeneration occur at the tissue level and are therefore not detectable as changes in morphology. Atpresent, there exists no effective way to objectively assess this element of cartilage health noninvasively.The lack of quantitative measures of cartilage condition hampers treatment planning and meaningfulassessment of joint injuries. Numerous MR-based methods have been proposed to noninvasively displayand quantitate changes in the composition and integrity of such elements of cartilage extracellular matrix(ECM) as proteoglycan (PG) and collagen content in vivo. Among techniques that have been applied inclinical subjects, T2 MRI is sensitive to several processes involved in cartilage degeneration. DelayedGadolinium-enhanced MRI of cartilage (dGEMRIC) provides an index that is most directly correlated to PGcontent, but relies on the selective uptake of intravenously administered contrast agent. T1rho MRI utilizesmagnetization preparation pulses without contrast administration, to yield parametric maps that alsocorrelate strongly with PG content. Clinical interpretation of MRI biochemical metrics is still unproven, eitherby clinical or by benchtop MRI-biochemistry studies. No studies have directly compared MRI measurementsin the clinic (in vivo) with MRI-biochemistry-biomechanics measurements on that same tissue in the researchenvironment (ex vivo), to build a bridge for direct translation of research results to clinical interpretation. Theresearch here proposed will test the hypothesis that noninvasive PG-sensitive MRI in combination withwater/collagen-sensitive MRI provides an early diagnostic measure of cartilage condition after acute injuryand at 2 years post-injury, as an objective evaluation of joint and articular health. We propose SA1) todirectly quantify the concordance between PG-sensitive in vivo clinical MRI and ex vivo MRI biochemicalmetrics with histochemical, biochemical, and biomechanical measurements within articular cartilagesections; SA2) to demonstrate a combination of T1rho/T2 relaxation sequence metrics as a biomarkertoassess cartilage health and mechanical function, SA3); to apply T1rho/T2 MRI clinically at time of injury as abenchmark for acute post-injury treatment effectiveness, and as a rehabilitation and outcomes measure.
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