The Effect of Mechanical Loading in Articular Cartilage Measured by Microscopic MRI

CBR member Yang Xia, of the Department of Physics, leads a team studying articular cartilage using several imaging tools including magnetic resonance imaging (MRI). In the July 7 issue of Physics in Medicine and Biology, post doc Nian Wang, Assistant Professor Edith Chopin from the Department of Chemistry, and Xia published a paper about The Effects of Mechanical Loading and Gadolinium Concentration on the Change of T1 and Quantification of Glycosaminoglycans in Articular Cartilage by Microscopic MRI (Volume 58, Pages 4535-4547). The research is described in the excerpt below from the introduction (references removed)

“The negatively charged glycosaminoglycans (GAG) in articular cartilage is responsible for the tissue stiffness; hence the reduction of GAG will weaken the mechanical properties of articular cartilage and can be regarded as an early sign of the tissue degradation. MRI relaxation measurements, which are sensitive to the motion of water molecules in tissue, have been used to detect the degradation of cartilage.

T1 [the spin-lattice relaxation time in nuclear magnetic resonance] in a native tissue is mostly uniform over the tissue depth … and isotropic with respect to the tissue orientation …. T1, however, can become sensitive to the GAG content in cartilage if a contrast agent (such as Gd(DTPA)2−) is administrated into the tissue. The paramagnetic gadolinium (Gd) ions are negatively charged and will distribute within articular cartilage in a spatially inversed relationship to the local GAG concentration, hence, influencing the tissue T1. In order to calculate a GAG image in cartilage quantitatively, two T1 maps are acquired before and after the Gd administration. The clinical version of this procedure has been termed as the dGEMRIC method in MRI literature.

The effect of loading on the tissue T1 by the dGEMRIC procedure was the subject of several recent MRI studies. In one high-resolution study, both modest and heavy compressions increased T1 significantly when the tissue was soaked in the 1 mM Gd solution. This trend of T1 increment in compressed tissue was, however, different from a human MRI study, where the mean T1 was found significantly decreased between the unloaded and loaded cartilage after the Gd administration…

The aim of this project was to resolve the above-discussed inconsistency between two MRI studies of T1 in compressed cartilage. Microscopic MRI (μMRI) was used to image both native and trypsin-degraded specimens that were immersed in various concentrations of gadolinium (up to 1 mM) and compressed at different strains (up to 50% strains). The imaging resolution across the tissue depth was 17.6 μm. Although this microscopic resolution is currently not possible in clinical MRI, it is essential for the accurate determination of the depth-dependent changes over the thickness of articular cartilage. This is because each sub-tissue zone in articular cartilage has a different thickness; the first pixel in any low-resolution (clinical) MRI therefore likely contains both the superficial and transitional zones of cartilage. Hence, the detection of any early lesion…would be weakened or even masked by the volume averaging. In contrast, the high-resolution μMRI will be able to localize the focal defects of cartilage and study the progression of early/local diseases. Since μMRI shares the same physics principles and engineering architectures as in clinical MRI, the μMRI data from this type of high-resolution MRI studies could serve as the guideline for the future development of clinical MRI in cartilage lesion detection.”

Xia’s research was supported by grants AR045172 and AR052353 from the National Institutes of Health. The research was carried out in the Bennett Nuclear Magnetic Resonance Facility, established through the generosity of Ronald B. and Janet N. Bennett.