Background/Purpose:

Musculoskeletal ultrasound (MS-US) has not been validated as a reliable technique to evaluate joint inflammation in an acute gout rabbit model. Rabbit has been used to accurately reproduce human acute gout. Thus, validating ultrasonographic imaging in this animal model would be important to use this technique for sequential evaluation of synovium damage, synovial fluid effusion, crystal deposits, and the efficacy of new pharmacological options.

Methods:

Monosodium urate (MSU) crystals were used to induce acute gout in 10 New Zealand white rabbits through bilateral intra-articular injections, while 3 controls received vehicle injection. Both rabbit knees were assessed by B-mode and power Doppler (PD) US blindly to the type of injection, both 24 and 72 h after the injections. All US examinations were carried out with a commercially available real-time scanner (LOGIQ e R7, GE Medical Systems) equipped with a 22 MHz linear transducer (6-15 MHz). B-mode and PD machine settings were optimised as follows: B-mode gain of 47 dB, dynamic range 72 dB, Doppler frequency of 14.3 MHz, Doppler gain of 28 dB, low-wall filters, and pulse repetition frequency of 700 Hz. B-mode global distension (GD), synovial fluid (SF) and synovial thickening (Sth); and PD-detected synovial blood flow (PD) were semiquantitatively scored (0-3) at the lateral recess of the knees. Additionally, the presence of MS-US features of MSU crystal deposit was investigated. Progression of joint swelling was followed by knee perimeter measurements. After 72 h, all rabbits were euthanized, and synovial membranes were fixed and embedded in paraffin for histological and immunohistochemical evaluation, and processed for protein expression studies.

Results:

We showed that MS-US was able to discriminate between the MSU crystal injected group and the control vehicle injected group for the different inflammatory findings both at 24 and 72 h (p<0.05). A statistically significant positive correlation was found between the increment in knee perimeter and GD MS-US at 24h (Spearman´s correlation coefficient r=0.579, p=0.0019). Sth MS-US score also showed a significant correlation with the global histopathological score in synovium paraffin sections measured by Krenn’s score (Spearman´s correlation coefficient r=0.466, p=0.018). Furthermore, PD intra-synovial US signal significantly correlated with the synovial tissue vascularization measured by % CD31 immunohistochemical positive staining (r=0.463, p=0.017). Additionally, we observed that GD MS-US significantly correlated with the protein levels of IL1β in the synovial membranes measured by western-blot studies (Spearman´s correlation coefficient r=0.529, p=0.0078).

Conclusion:

Our results indicate that MS-US imaging measurements correlate with joint swelling, histological inflammation and vascularization of the synovium. Furthermore, MS-US could also serve as an indicator of the inflammatory degree in relation to the level of some pro-inflammatory cytokines, such as IL-1β, involved in the pathogenesis of gout. Therefore, ultrasonography analysis can be considered a feasible valid method for assessing the evolution of synovial inflammation in experimental gouty arthritis in rabbits.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/performance-and-validity-of-musculoskeletal-ultrasound-in-the-assessment-of-synovial-inflammation-in-experimental-acute-gout/