Value of future epidemiologic research in OA: The art and science of selecting an appropriate study design

s / Osteoarthritis and Cartilage 23 (2015) A17eA25 A23 diffusion-weighted imaging. Evaluation of the glycosaminoglycan (GAG) matrix in cartilage can be done with delayed gadolinium enhanced MRI of cartilage (dGEMRIC), T1rho relaxation time measurements, sodium MRI, and chemical exchange saturation transfer (gagCEST). In addition, evaluation of cartilage and other tissues under load (biomechanics) is also possible with MRI. All of these method have advantages and drawbacks that may make them more appropriate to a given imaging situation or study. Conclusions: A variety of MRI methods to evaluate a joint with osteoarthritis are available. The methods of choice in a particular study depend on many factors, including hardware available, the joint being studied, and imaging time. Emphasis will be placed on the trade-offs between the methods and goals of the imaging study. Study of tissue composition with MRI may be particularly helpful in disease initiation. Once OA is established, study of tissue morphology with MRI can be done quantitatively or with semi-quantitative scoring. I-23 VALUE OF FUTURE EPIDEMIOLOGIC RESEARCH IN OA: THE ART AND SCIENCE OF SELECTING AN APPROPRIATE STUDY DESIGN E. Losina. Boston Univ. Sch. of Publ. Hlth., Boston, MA, USA During the session we will discuss how to optimize the study design and to ensure it enables researchers to offer a new informative insight toward the clinical question under study.Wewill discuss how to choose among several clinical questions to optimize the likely impact of future research study. We will address the topics of resource prioritization. In addition the audience will be introduced to the concept of Value of Information. We will also cover use and misuse several commonly used statistical methods in analysis of clinical studies in OA. I-24 CURRENT STATUS OF THE ART IN COMPOSITIONAL IMAGING OF JOINT TISSUES T.M. Link. Univ. of California San Francisco, San Francisco, CA, USA Purpose: To review technologies currently used to assess the biochemical composition of joint tissues and discuss their pros and cons. Methods available: During the last decade a number of compositional technologies have been established and studied mostly using quantitative MRI. These include T2 mapping, T1rho, dGEMRIC (delayed Gadolinium enhanced MRI of the cartilage), Sodium-23-imaging and gagCEST (glycosaminoglycan chemical exchange saturation transfer) imaging to quantify cartilage andmeniscal biochemical composition. T2 mapping is currently the most widely used technology and most information is available on this imaging biomarker, which provides quantitative data on water content and collagen integrity of the cartilage and menisci. According to previous in vitro studies T1rho characterizes the amount of macromolecules within the tissue, which correlates with the amount of proteoglycans. dGEMRIC requires the injection of negatively charged Gadolinium contrast agents which provide quantitative information on the amount of negatively charged glycosaminoglycans. Both Sodium imaging and gagCEST target the concentration of glycosaminoglycans, but require imaging at higher field strength. Quantitative CT has also been used in vivo to assess glycosaminoglycan concentration in hyaline cartilage but it requires the injection of contrast agents into the joint and there is radiation exposure. Results of previous studies: Previous studies showed that imaging biomarkers of cartilage composition had good reproducibility and validated these biomarkers both in an in vitro setting and clinically. In 2011 a multi-center ACRIN trial was published which documented that in a Multi-Center, Multivendor environment knee cartilage T2, and patellar T1-rho demonstrated moderate to excellent reproducibility (1). Similarly phantom measurements over 8 years in the Osteoarthritis Initiative environment showed good reproducibility of T2 relaxation times varying from 1.5 to 5.3% (2). Single center studies found good reproducibilities for dGEMRIC while less consistent data is available for some the newer techniques such as gagCEST and quantitative CT arthrography. In vitro studies showed that T1rho, T2 and dGEMRIC measurements correlated with histological assays of proteoglycan and collagen as well as mechanical properties of cartilage (3, 4). Clinical studies documented differences in T1rho, T2 and dGEMRIC measurements between patients with early osteoarthritis and normal controls and one recent study showed that T2 measurements predicted radiographic onset of knee osteoarthritis in a longitudinal study from the OAI (5). Longitudinal studies also showed that T2 measurements increased over time in normal populations, and were sensitive to weight loss and physical activity. Problems, however, have been found in using measures of cartilage composition in more advanced degenerative disease. Conclusion: A number of imaging biomarkers of joint composition are available, which have been validated and shown to have good reproducibility. T1rho, T2 and dGEMRIC are currently the imaging biomarkers, which are best established with most studies having been performed using T2 relaxation time measurements. References: 1. Mosher TJ, Zhang Z, Reddy R, et al. Knee articular cartilage damage in osteoarthritis: analysis of MR image biomarker reproducibility in ACRIN-PA 4001 multicenter trial. Radiology. 2011;258(3):832-42. 2. Schneider E, Nessaiver M. The Osteoarthritis Initiative (OAI) magnetic resonance imaging quality assurance update. Osteoarthritis Cartilage. 2013;21(1):110-6. 3. Li X, Cheng J, Lin K, et al. Quantitative MRI using T1rho and T2 in human osteoarthritic cartilage specimens: correlationwith biochemical measurements and histology. Magn Reson Imaging. 2011;29(3):324-34. 4. Nissi MJ, Toyras J, Laasanen MS, et al. Proteoglycan and collagen sensitiveMRI evaluation of normal and degenerated articular cartilage. J Orthop Res. 2004;22(3):557-64. 5. Liebl H, Joseph G, Nevitt MC, et al. Early T2 changes predict onset of radiographic knee osteoarthritis: data from the osteoarthritis initiative. Ann Rheum Dis. 2014 in press. I-25 SOXC TRANSCRIPTION FACTORS IN SKELETOGENESIS AND CARTILAGE DIFFERENTIATION V. Lefebvre, P. Bhattaram. Cleveland Clinic Lerner Res. Inst., Cleveland, OH,