Detection of changes in articular cartilage proteoglycan by T_1ρ magnetic resonance imaging

Abstract

The purpose of this work is to demonstrate the feasibility of TI,,-weighted magnetic resonance imaging (MRI) to quantitatively measure changes in proteoglycan content in cartilage. The TI, MRI technique was implemented in an in vivo porcine animal model with rapidly induced cytokine-mediated cartilage degeneration. Six pigs were given an intra-articular injection of recombinant porcine interleukin-1 p (IL-1 p) into the knee joint before imaging to induce changes in cartilage via matrix metalloproteinase (MMP) induction. The induction of MMPs by IL-1 was used since it has been extensively studied in many systems and is known to create conditions that mimic in part characteristics similar to those of osteoarthritis. The contralateral knee joint was given a saline injection to serve as an internal control. T1,-weighted MRI was performed on a 4 T whole-body clinical scanner employing a 2D fast spin-echo-based T I , imaging sequence. T I , relaxation parameter maps were computed from the TI,-weighted image series. The average TI,, relaxation rate, RIP (l/T,,) of the IL-lp-treated patellae was measured to be on average 25% lower than that of saline-injected patellae indicating a loss of proteoglycan. There was an average reduction of 49% in fixed charge density, measured via sodium MRI, of the IL-1 b-treated patellae relative to control corroborating the loss of proteoglycan. The effects of 1L-1 p, primarily loss of PG, were confirmed by histological and immunochemical findings. The results from this study demonstrate that R,,, is able to track proteoglycan content in vivo.

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage

“…This is completely in conflict with several results from IL-1b studies on a larger group of samples and on an in vivo animal model where a significant increases in T 1r ( Figure 25) were observed (54,177). (3) At the higher field (8.5 T), T 1r should be lower than that at 1.5 T, but the T 1r numbers measured in human cartilage in this study are almost 50% higher than those observed at 1.5 T. This result was not explained.…”

“…Genetic evidence for a role of IL-1b in OA came much more recently with the discovery of polymorphisms in the IL-1 gene cluster that act as risk factors for OA (51)(52)(53). In arthritis imaging research, IL-1b is now used to simulate osteoarthritis in animal models in order to track progression of mild disease by emerging techniques (54).…”

“…Correlation of changes in cartilage biomechanical and biochemical properties with T 1r relaxation rate was made in a cytokine-induced model of osteoarthritic condition (54). T 1r mapping was performed at 4.7 T, and PG, collagen and water content were measured via biochemical assays.…”

“…The potential of T 1r mapping in detecting rapidly induced cytokine-mediated cartilage degeneration in porcine animal model in vivo was investigated (54). Six Yorkshire pigs were given an intra-articular injection of recombinant porcine interleukin-1b in the knee joints before imaging.…”

Noninvasive Quantification of Human Nucleus Pulposus Pressure with Use of T1ρ-Weighted Magnetic Resonance Imaging

“…Other techniques, including delayed gadoliniumenhanced and sodium magnetic resonance imaging, may have sufficient sensitivity but there are also substantial limitations with regard to implementation of these methods [9][10][11] . T1r-weighted imaging is a spin-lock magnetic resonance imaging technique that shows promise as a noninvasive biomarker, as several in vivo studies have demonstrated the clinical feasibility of evaluating both intervertebral disc and articular cartilage with this modality [12][13][14][15] . The spin-lock technique was first employed by Redfield in 1955 and allows for a lower Larmor frequency 16 .…”