【Animal Modeling】-Transcranial ultrasound perfusion imaging performance and safety evaluation in rats after skull thinning

  Objective: To observe and quantitatively evaluate the performance of right brain transcranial ultrasound perfusion imaging by thinning the local skull of SD rats to improve the acoustic window, and to preliminarily evaluate the effect of bone grinding and transcranial ultrasound on the blood-cerebrospinal fluid barrier.

  Methods: Forty-eight SD rats were divided into two groups: A and B. Six rats in group A underwent transcranial ultrasound perfusion imaging before and after the right local skull thinning to compare the imaging effects. Brain Evans blue (EB) staining was performed on 4 rats, and 2 rats were subjected to head magnetic resonance imaging (MRI). After sacrifice, the skull bones on both sides were taken for H&E staining to measure the thickness of the remaining skull after grinding. B A group of 42 rats underwent right brain transcranial ultrasound perfusion imaging at the optic chiasm plane after thinning the right partial skull (bolus injection of 0.15 mL of ultrasound contrast agent SonoVueTM), and dynamic contrast-enhanced ultrasound analysis (time-intensity curve) was performed to obtain the ground skull. Transcranial ultrasound perfusion imaging parameters of normal rat brain. Results The effect of right cerebral perfusion imaging in SD rats after bone grinding was significantly improved, showing the characteristics of "rapid enhancement, rapid washout, and slow clearance". Time-intensity curve quantitative analysis results: peak Intensity (PI) after skull grinding was about 3 times higher than before skull grinding [(9.98±2.35) vs (3.24±1.49) dB, P<0.01], while="" time="" to="" peak="" did="" not="" change="" significantly="" vs="" p="">0.01]. The thickness of the right skull after thinning was about (66.1±11.4) μm; EB staining and MRI examinations did not reveal obvious blood-cerebrospinal fluid barrier damage.

  Conclusion: Skull thinning surgery has no obvious damage to the brain tissue of SD rats and can significantly improve the effect of transcranial ultrasound perfusion imaging. This technique can be used for quantitative analysis of transcranial ultrasound perfusion imaging in small animals. This minimally invasive, real-time imaging method It can be used to study the dynamic changes of cerebral blood flow in various small animal pathological models.