Quantitative and qualitative assessment of articular cartilage in the goat knee with magnetization transfer imaging Didier Laurent*, James Wasvary, Jianyun Yin, Markus Rudin, Theodore C. Pellas, Elizabeth O’Byrne Core Technology Area, Novartis Pharmaceuticals Corporation, 556 Morris Avenue, Summit, NJ, USA Received 30 May 2001; accepted 6 August 2001 Abstract We investigated the role of collagen in the magnetization transfer (MT) effect in contrast to other macromolecules. By means of phantoms made of collagen, chondroitin sulfate (CS) and albumin, MR parameters have been optimized in order to reduce the acquisition time and improve the sensitivity, as well as to minimize the contributions from CS and albumin to the MT induced signal attenuation. The same method was used to study cartilage ex vivo (bovine articular and nasal cartilage plugs) and in vivo (goat knee femoral chondyle). In phantom samples, the MT signal attenuation depended on the collagen concentration while contributions from the other macromolecules were found to be minimal. In average, analysis of MT images revealed a 25%, 35% and 30% signal attenuation in 10% w/v type I collagen gels, cartilage plugs, and cartilage from the weight-bearing areas of the goat knee, respectively. Biochemical data revealed that treatment of cartilage plugs with bacterial collagenase led to collagen depletion and correspondingly to a decrease of the MT response. In contrast, trypsin-induced proteoglycan loss in cartilage plugs did not alter the MT effect. A significant correlation was observed between the collagen content in these plugs and their respective MT ratios and the rate constant k for the exchange process bound versus free water. Finally, data obtained from in vivo MT measurement of the goat knee demonstrated that intra-articular injection of papain might not only cause degradation of proteoglycans but also a change in collagen integrity in a dose-dependent manner. We conclude that in vivo measurement of MT ratios gives quantitative and qualitative information on the collagen status and may be applied for the routine evaluation of normal and abnormal articular cartilage. © 2001 Elsevier Science Inc. All rights reserved. Keywords: Magnetization transfer; Osteoarthritis; Cartilage; Collagen 1. Introduction Osteoarthritis (OA) is a degenerative disease, which pri- marily results from biomechanical failure of the cartilage matrix. Among leading theories, structural damage to the collagen network which constitutes up to 50 – 60% of the dry weight of articular cartilage [1], may play a major role in the etiology of OA. Type II collagen, the most abundant form of collagen (80 –95%) in articular cartilage [2], is characterized by extensive cross-linking restricting the mo- lecular motion and being associated to potentially fewer sites for hydration. By comparison, Type I collagen which can be found predominant in tendons contains less cross- linked fibrils and shows a much higher level of hydration. Assuming that both the collagen content and its degree of cross-linking varies with location, age and pathology, the resulting change in its hydration property is likely to influ- ence functional integrity of cartilage. Magnetization transfer (MT) imaging probes the ex- change of magnetization between bulk (mobile) water pool and the water pool bound to macromolecules such as col- lagen and hence shows promise as a method that can non- invasively examine the severity of cartilage abnormality. By selectively saturating the broad signal of macromolecule bound water, the MRI observable resonance of the bulk water is attenuated, the degree of the signal reduction de- pending on the exchange rate and on T 1 relaxation. Carti- lage is known to display significant MT effect with respect to its high content of collagen [3] which can be exploited for improved contrast and consequently for a better delineation of articular structures [4,5]. In addition MT imaging will provide information on the chemical/structural status of * Corresponding author. Tel.: +1-908-277-5231; fax: +1-908-277- 7250. E-mail address: didier.laurent@pharma.novartis.com (D. Laurent). Magnetic Resonance Imaging 19 (2001) 1279 –1286 0730-725X/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S0730-725X(01)00433-7