MRI Biomarkers in Assessing Articular Cartilage Health

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Magnetic resonance imaging (MRI) maintains its position as the gold standard for visualization of cartilage defects and overall assessment of cartilage morphology. However, the earliest markers of cartilage degeneration occur at the tissue level and are therefore not detectable as changes in morphology. At present, 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 meaningful assessment of joint injuries. Numerous MR-based methods have been proposed to noninvasively display and 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 in clinical subjects, T2 MRI is sensitive to several processes involved in cartilage degeneration. Delayed Gadolinium-enhanced MRI of cartilage (dGEMRIC) provides an index that is most directly correlated to PG content, but relies on the selective uptake of intravenously administered contrast agent. T1rho MRI utilizes magnetization preparation pulses without contrast administration, to yield parametric maps that also correlate strongly with PG content. Clinical interpretation of MRI biochemical metrics is still unproven, either by clinical or by benchtop MRI-biochemistry studies. No studies have directly compared MRI measurements in the clinic (in vivo) with MRI-biochemistry-biomechanics measurements on that same tissue in the research environment (ex vivo), to build a bridge for direct translation of research results to clinical interpretation. The research here proposed will test the hypothesis that noninvasive PG-sensitive MRI in combination with water/collagen-sensitive MRI provides an early diagnostic measure of cartilage condition after acute injury and at 2 years post-injury, as an objective evaluation of joint and articular health. We propose SA1) to directly quantify the concordance between PG-sensitive in vivo clinical MRI and ex vivo MRI biochemical metrics with histochemical, biochemical, and biomechanical measurements within articular cartilage sections; SA2) to demonstrate a combination of T1rho/T2 relaxation sequence metrics as a biomarkerto assess cartilage health and mechanical function, SA3); to apply T1rho/T2 MRI clinically at time of injury as a benchmark for acute post-injury treatment effectiveness, and as a rehabilitation and outcomes measure.