Value of contrast-enhanced ultrasound for detection of synovial vascularity in experimental rheumatoid arthritis: an exploratory study

Abstract

ObjectiveThis study aimed to examine the associations between contrast-enhanced ultrasound (CEUS) imaging and synovial hypervascularity and synovitis score in a rabbit model of antigen-induced arthritis (AIA), compared with power Doppler ultrasound (PDUS).MethodsWe investigated 50 knee joints in 25 AIA rabbits (AIA group), and 10 knee joints in five sham-injected rabbits (control group). PDUS and CEUS images were evaluated at the 8th week. Ultrasound-guided synovial biopsies were targeted in the area with hypervascularity, and synovial microvessel density (MVD) was evaluated by immunohistochemical staining of CD31.ResultsThe PDUS score was significantly higher in the AIA group (2.61 ± 0.78) compared with the control group (0.50 ± 0.53). CEUS in the AIA group revealed a fast-in/slow-out pattern of contrast enhancement. MVD revealed by CD31+ vessel count and the synovitis score were significantly higher in the AIA group compared with the control group. In the AIA group, CEUS findings showed a better correlation with MVD revealed by CD31+ and synovitis score than PDUS findings.ConclusionCEUS is superior to PDUS for estimating synovial hypervascularity and hyperplasia in experimental rheumatoid arthritis.

Evaluation of Liposome-Loaded Microbubbles as a Theranostic Tool in a Murine Collagen-Induced Arthritis Model

“…Although ultrasound imaging of the joint synovium is more complex due to the presence of surrounding articulate bones (i.e., femur and tibia in the knee joint) (Figure 2B), the synovial cavity and synovial microbubble influx could be clearly visualized (Figure 2D). However, we could not detect any differences in the maximal contrast enhancement and time to peak of the contrast-enhanced ultrasound signal between healthy and inflamed synovia, which differs from results obtained in humans [12,[71][72][73]. A possible explanation for this discrepancy may lie in the difference in microvasculature size between humans and mice.…”

“…A possible explanation for this discrepancy may lie in the difference in microvasculature size between humans and mice. Whereas the microvasculature in human knee joints (d = 11 µm) [104] is known to be large enough to permit CEUS imaging with micron-sized microbubbles [12,71,73], Raatz et al determined that the murine neo-vasculature in CIA knee synovia is about 2-times smaller (d = 5.8 µm), which may already hamper efficient microbubble perfusion [81]. In addition, Raatz et al found that the functionality of the synovial vasculature is significantly decreased [81,105,106].…”

“…They are then deposited onto the cell membrane in the wake of the translating microbubble gas core, a process we termed sonoprinting [67,70]. Given promising preliminary results on the use of ultrasound and CEUS for RA diagnosis in humans [10][11][12][13][14][71][72][73], there is tremendous interest in using the same bubbles for local drug delivery purposes. Here, we first investigate whether CEUS can be a useful tool to quantify neovascularisation in arthritic mice.…”

Musculoskeletal and Nerve Ultrasonography

“…Additional information during US imaging can be obtained through sonoelastography and contrast-enhanced ultrasonography (CEUS) [11][12][13][14][15]. These two US techniques have been studied and proven their usefulness in certain rheumatic diseases, but nevertheless, they are not so widely used as conventional gray scale (GS) and Doppler modalities.…”

“…CEUS can assess joint inflammation and provides a view of the exact vascular patterns, which can also be visible in inflamed sacroiliac joints [10,18]. Some studies report the superiority of CEUS compared to power Doppler US in detecting synovial hypervascularity [14,15]. Compared to the known risks of using contrast agents in MRI and CT, contrast agents used in CEUS have no proof of significant side-effects.…”