Magnetic resonance imaging of proteoglycans in cartilage

Cartilage is a dense connective tissue which protects the underlying bone of synovial joints, while ensuring smooth articulation and movement. Degenerative diseases of cartilage result in progressive cartilage destruction and thus affects the normal joint function. Despite the compelling need mandated by the prevalence and morbidity of degenerative cartilage diseases, it is extremely difficult to study disease progression and therapeutic efficacy either in vitro or in vivo. This is partly because no techniques have been available for nondestructively visualizing the distribution of functionally important macromolecules in living cartilage.

Proteoglycans (PGs) are one of the major solid components of cartilage extracellular matrix and play a significant role in mechanical support function in normal cartilage. Degenerative disease of cartilage is characterized by a loosening of cartilage extracellular matrix and loss of proteoglycans. In this work I have developed a magnetic resonance imaging technique (MRI) to image and quantify the proteoglycan concentration in cartilage nondestructively. The technique was also validated for diseased human tissue to demonstrate that PG concentration can be measured over a large range (nearly normal to totally degraded) of PG concentration in cartilage. Clinical feasibility of this technique to measure PG in human cartilage in vivo was also investigated showing that it is possible to monitor PG distribution in vivo.

This technique gives us a unique opportunity to image a specific macromolecule nondestructively in vitro or in vivo. As it relies on proton magnetic resonance it is widely available and the high signal to noise allows for the high resolution imaging of cartilage. This method is applicable to a wide range of applications, from living tissue in culture on a near-histologic scale, to isolated samples in vitro, to in vivo clinical (or animal) studies. We now have a unique opportunity to study developmental and degenerative disease processes in cartilage and monitor the efficacy of medical and surgical therapeutic measures, for ultimately achieving a greater understanding of cartilage physiology in health and disease. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)