Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla.

OBJECTIVE: Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis. METHODS: We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO2) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical-histological data were measured by correlation coefficients. RESULTS: Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = -0.51, p = 0.02) and excellently on day 28 (r = -0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees. CONCLUSION: The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields. KEY POINTS: • BOLD and DCE MRI detect interval perisynovial changes in a rabbit knee • BOLD and DCE MRI act as surrogate markers of physiologic changes in arthritis • BOLD MRI signal represents oxygen extraction compared with intra-articular PO 2 • DCE MRI measurements estimate physiologic periarticular vascular properties • In rabbit knees with acute arthritis, BOLD/DCE MRI highly correlated with histological scores.

Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 tesla.

BACKGROUND: Blood-oxygen-level-dependent (BOLD) MRI has the potential to identify regions of early hypoxic and vascular joint changes in inflammatory arthritis. There is no standard protocol for analysis of BOLD MRI measurements in musculoskeletal disorders. OBJECTIVE: To optimize the following BOLD MRI reading parameters: (1) statistical threshold values (low, r > 0.01 versus high, r > 0.2); (2) summary measures of BOLD contrast (percentage of activated voxels [PT%] versus percentage signal difference between on-and-off signal intensities [diff_on_off]); and (3) direction of BOLD response (positive, negative and positive + negative). MATERIALS AND METHODS: Using BOLD MRI protocols at 1.5 T, arthritic (n = 21) and contralateral (n = 21) knees of 21 juvenile rabbits were imaged at baseline and on days 1, 14 and 28 after a unilateral intra-articular injection of carrageenan. Nine non-injected rabbits served as external control knees (n = 18). By comparing arthritic to contralateral knees, receiver operating characteristic curves were used to determine diagnostic accuracy. RESULTS: Using diff_on_off and positive + negative responses, a threshold of r > 0.01 was more accurate than r > 0.2 (P = 0.03 at day 28). Comparison of summary measures yielded no statistically significant difference (P > 0.05). Although positive + negative (AUC = 0.86 at day 28) and negative responses (AUC = 0.90 at day 28) for PT% were the most diagnostically accurate, positive + negative responses for diff_on_off (AUC = 0.78 at day 28) also had acceptable accuracy. CONCLUSIONS: The most clinically relevant reading parameters included a lower threshold of r > 0.01 and a positive + negative BOLD response. We propose that diff_on_off is a more clinically relevant summary measure of BOLD MRI, while PT% can be used as an ancillary measure.

A study of high frequency ultrasound scattering from non-nucleated biological specimens.

The high frequency backscatter from cells with a nucleus to cell volume ratio of 0.50 cannot be adequately modeled as a homogeneous sphere. It was hypothesized that the cytoplasm of such cells is of fluid nature. This work attempts to model the ultrasound backscatter (10-62 MHz) from some non-nucleated biological specimens. This was done by measuring the backscatter response from individual sea urchin oocytes and comparing it to theoretical predictions in both the time and frequency domains. A good agreement was found between the experimental and theoretical results suggesting that the non-nucleated oocytes are of fluid nature.