A novel rat model of cerebral small vessel disease and evaluation by super-resolution ultrasound imaging

Cerebral small vessel disease (CSVD), which causes cognitive, functional and emotional decline, is related to stroke events, and it is a major cause of Alzheimer's disease. In the social context of an aging population, the incidence of CSVD is on the rise yearly, and the exact pathogenesis is still controversial and remains unclear. Exploring the pathological mechanism of CSVD on the histological level using animal models is important for the investigation of new clinical diagnostic methods and treatment options. The existing surgical CSVD model preparation methods are difficult to operate and cannot control the injury location or degree. This study used ultrasound combined with microbubbles (MBs) to induce an easy-to-operate and non-invasive animal model of CSVD with controllable location and degree. The rat model was evaluated from the perspective of histology, ethology, and imageology, respectively. In addition, we utilized super-resolution ultrasound imaging (SR-US) technology to directly observe the microvessels of the model. The histological results showed that the modeling was successful in the preset position, and neurology deficits were observed in 62.5% of 8 rats. The SR-US results of one rat showed that compared with the non-sonication region, the number of cerebral small blood vessels discovered in the sonication area was reduced (43 vs 11), the blood flow speed decreased significantly (p<0.001), and blood flow volume decreased (144.7 vs 11.7 uL/s) because of vasoconstriction. This study provides a new modeling method with controllable damage location and degree for the study of CSVD, and SR-US is found to be an effective evaluation method, which can directly assess the hemodynamic changes of CSVD in vivo . • The operation of this CSVD model using ultrasound combined with microbubbles is easy and non-invasive. • The location of brain injury can be specified and the degree is controllable. • This model was validated in terms of histology, ethology and imaging technology. • Super-resolution ultrasound imaging has the advantage of being capable of quantitatively analyzing the structural and hemodynamic changes of microvessels in vivo.