Future spectroscopic diagnostics in osteoarthritis

Abstract

Imaging of musculoskeletal tissues is an important aspect of diagnostic and therapeutic rheumatology. The past 20 years have witnessed the development and refinement of multiple technical platforms for imaging of musculoskeletal tissues. In addition to conventional radiographs, these include computed tomography, magnetic resonance imaging, and ultrasound [1]. Each of these platforms provide important and often complementary diagnostic and disease progression information to the clinical rheumatologist. However, every one of these platforms fails to provide critical information about the structural composition of extracellular matrix (ECM) components at the molecular level. There is increasing experimental evidence that molecular changes in ECM components may determine macroscopic changes in bone, tendon, synovium and cartilage, which are recognized by available imaging techniques and associated with clinical disease. Therefore, an unmet medical need remains for imaging technologies that can identify early molecular changes in ECM components that may predict disease risk or progression. Over the same period of time, there has been extensive development of visible and infrared light-based vibrational spectroscopy techniques for the study of complex organic polymers, including ECM of musculoskeletal tissues. These studies owe much to extensive research on the spectroscopy of synthetic polymers of industrial interest, including the ultrahigh-molecularweight polyethylene used in artificial joint implants. Much of the effort has been directed at the analysis of bone ECM, but in the last few years, several groups have also begun to investigate the spectroscopic properties of articular cartilage ECM. The term ‘vibrational spectroscopy’ includes several very different techniques that share the ability to detect and analyze molecular vibrations: the bending and stretching motions of the chemical bonds that hold organic molecules together. The strength of these methods is that molecular vibrations occur as specific and well-known optical frequencies. The vibrational spectrum represents an optical fingerprint for a given complex organic molecule. For example, collagen proteins are a major ECM component in bone, tendon and articular cartilage, and, at a molecular level, are derivatized organic polymers composed of repetitive amide linkages. Since structural collagens are characterized by long half lives, aging or disease can cause alterations in the secondary structure of the collagen fibrils that will be characterized by small changes in the vibrational frequencies and intensities of the amide backbone spectra. Because vibrational spectroscopy is unfamiliar to most rheumatologists, we will briefly review the basis for several available methods, discuss the current research using osteoarthritis (OA) as a disease model, and assess prospects for clinical application in OA. Introductory texts on both infrared [2] and Raman [3] spectroscopy are available, and although these are aimed at advanced undergradutate chemistry students, they should be easily understood by anyone who has completed approximately 2 years of college chemistry.