Yang Xia studies cartilage using Magnetic Resonance Imaging

Professor and CBR member Yang Xia, of the Department of Physics, leads a team of researchers studying cartilage and its role in arthritis. In the June 2011 issue of the journal Magnetic Resonance in Medicine, Xia and his team reported on Strain-Dependent T1 Relaxation Profiles in Articular Cartilage by MRI at Microscopic Resolutions (Volume 65, Pages 1733-1737). In a typical Magnetic Resonant Imaging experiment, a tissue is placed in a large static magnetic field that lines up the magnetic moments of the hydrogen nuclei (many of which are in water molecules), producing a net magnetization. Then researchers excite the system using a second, radio-frequency magnetic field and measure the time constant for the decay of the magnetization. Two time constants can be detected: T1 governing the decay of the magnetization parallel to the static magnetic field, and T2 controlling the decay perpendicular to the static field. These time constants contain different information about the health of the tissue. In the introduction to their article, Xia et al. describe their goals and state the significance of their work (For brevity, I have removed citations to other papers).

“Magnetic resonance imaging (MRI) has been used extensively to study the degradation of articular cartilage, which is a hallmark of osteoarthritis and related joint diseases that affect an increasingly large portion of the human population. The difficulties in a reliable detection of early tissue degradation using imaging are due to several factors. First, articular cartilage is a thin layer of tissue (typically 0.5–2 mm) with a number of complex depth-dependent properties, in particular a depth-dependent orientation of collagen fibrils and a depth-dependent glycosaminoglycan (GAG) concentration. Second, the degradation of cartilage at the early stages is marked by a set of intertwined changes in its molecular, chemical, and enzymatic concentrations and activities; hence, any early maker must be sensitive to these molecular level changes. Third, the early degradations tend to be focal and small, which requires a high resolution in imaging.

Among the MRI parameters that are sensitive to the tissue degradation, T2 relaxation is commonly used in basic research and clinical diagnostics because of its sensitivity to the collagen orientation and water content. In contrast, T1 relaxation in the native tissue has been found mostly homogeneous over the tissue depth and isotropic to the tissue orientation in the magnet. The clinical potential of T1 in MRI of cartilage was noticed largely due to a MRI procedure known as the dGEMRIC method (delayed gadolinium-enhanced MRI of cartilage), which dopes the tissue/patient with paramagnetic ions, gadolinium (Gd). Based on the assumption that charged mobile ions distribute in cartilage in an inverse relation to the concentration of the negatively charged GAG molecules, the acquisition of two T1 images, before and after a patient is injected with a charged MRI contrast agent, Gd(DTPA)2-, enables the construction of a GAG image in cartilage. Any local deficiency of GAG can be interpreted as a cartilage lesion.

As articular cartilage is a load-bearing tissue that is being compressed constantly daily, MRI experiments of a compressed cartilage have been carried out at both microscopic resolutions and clinical settings. This study concerns any strain dependency in the T1 profiles in the absence and presence of Gd(DTPA)2- in (canine) articular cartilage. A μMRI procedure was used to image the ex vivo tissue blocks at microscopic resolution (17.6-μm pixel resolution). We hypothesized that the T1 profiles in articular cartilage would be depth dependently sensitive to mechanical strains, which could affect any quantitative determination of GAG concentrations in cartilage.

Coauthors Ji Hyun Lee and Farid Badar are both graduate students in the Biomedical Sciences: Medical Physics PhD program, and Nian Wang is an Assistant Research Scientist. Xia’s research team is supported by two grants from the National Institutes of Health. The research was performed using the Bennett Nuclear Magnetic Resonance facility, established through the generosity of Ronald B. and Janet N. Bennett.