Quantitative Radiologic Imaging Techniques for Articular Cartilage Composition: Toward Early Diagnosis and Development of Disease‐Modifying Therapeutics for Osteoarthritis

Introduction Osteoarthritis (OA) is the most common degenerative joint disease affecting articular cartilage and other joint tissues, resulting in serious morbidity and large socioeconomic impact (1–3). In the US, 27 million people experienced OA in 2005 (4). The total cost attributed to arthritis and other rheumatic conditions in the US was 128 billion dollars in 2003 (5,6). Due to an aging population and increasing obesity rates, OA will become even more prevalent in the next decades with an estimated 67 million Americans expected to be diagnosed with arthritis by 2030 (7). The final treatment option for OA is joint replacement, which is associated with complications, limited durability, and contributes to the high costs of OA. Consequently, current OA research focuses on strategies that may be disease modifying, such as disease-modifying osteoarthritis drugs, chondrocyte implantation, stem cell therapy, or high tibial osteotomy (8–10). Attention is also focused on measures that may prevent or delay OA onset, including lifestyle interventions. These strategies all target OA at an early stage when they are most effective, thereby avoiding or delaying joint replacement. In order for therapeutic approaches to OA to be successful, monitoring of their effectiveness with accurate, sensitive, and objective imaging techniques is essential. Clinical OA measurements, such as pain, remain important, but are subjective and correlate poorly with disease severity (11,12). Radiography is used to stage and follow OA, but it cannot depict articular cartilage directly and correlates weakly with cartilage damage on arthroscopy (13,14). Furthermore, radiography is incapable of detecting early OA and subtle OA changes (15,16), and often does not correlate with OA symptoms (17,18). Magnetic resonance imaging (MRI) is useful in OA because cartilage and other joint structures can be assessed for morphologic changes more reliably than on radiography (19,20). Several semiquantitative MRI scoring systems for OA have been developed, such as the Knee Osteoarthritis Scoring System (21), the Whole-Organ Magnetic Resonance Imaging Score (22), the Boston Leeds Osteoarthritis Knee Score (23), and the MRI Osteoarthritis Knee Score (24,25). Cartilage segmentation followed by thickness or volume measurements increase sensitivity further (26,27). Morphologic changes, however, are not always present in early-stage OA and may not change significantly with disease progression. In addition, conflicting reports have been published on the association between cartilage defects on morphologic MRI and pain or other OA symptoms (28,29). Therefore, MRI methods that rely on morphology may fail to capture early OA onset or subtle changes in disease severity (30). Because of the limitations of radiography and traditional MRI methods, there is need for new imaging modalities to not only advance our understanding of the pathogenesis of OA, but to provide novel end points to accelerate development of therapies. In the future, use of imaging to identify asymptomatic individuals in a “pre-OA” state may identify individuals for whom therapeutic intervention could prevent the subsequent development of OA. Novel imaging techniques that enable measurement of the biochemical composition of cartilage rather than its morphology show promise to fulfill this need (31,32). These techniques offer numerical outcome measures that can be used as imaging biomarkers for cartilage quality in research on OA and other joint diseases. In addition, they may enhance understanding of the pathogenesis of OA. A Edwin H. G. Oei, MD, PhD: Stanford University, Stanford, California, and Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Jasper van Tiel, MD: Erasmus MC, University Medical Center, Rotterdam, The Netherlands; William H. Robinson, MD, PhD: Stanford University, Stanford, California, and VA Palo Alto Health Care System, Palo Alto, California; Garry E. Gold, MD: Stanford University, Stanford, California. Dr. Gold has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Isto, Zimmer, and Boston Scientific, and has received research support from GE Healthcare. Address correspondence to Garry E. Gold, MD, Department of Radiology, Stanford University, 1201 Welch Road, P-271, Stanford, CA 94305-5488. E-mail: gold@stanford.edu. Submitted for publication October 18, 2013; accepted in revised form February 18, 2014. Arthritis Care & Research Vol. 66, No. 8, August 2014, pp 1129–1141 DOI 10.1002/acr.22316 © 2014, American College of Rheumatology