A preliminary in-vivo porcine study of long pulse histotripsy for thrombolysis of intraventricular hemorrhagic clot

Abstract

Intraventricular hemorrhage is primarily a condition of premature babies where 40% will develop a form of bleeding that occupies >50% of the ventricles in the brain. Due to the fragile nature of patient, there is no treatment except the use of shunts for cerebrospinal fluid accumulation. Long pulse histotripsy (LPH) uses focused ultrasound pulses as a method to non-invasively target and mechanically break up the clot. An in-vivo IVH procine model has been developed and it is used to test the efficacy and safety of using LPH on a Philips Sonalleve. The IVH model has an average clot volume of 3986 mm3 and present in both ventricles. To simulate a neonatal patient, a craniotomy has been performed. The acoustic parameters used are as follows: freq. 1.2 MHz, 2x6 mm focus, 10 ms pulse duration, 10,000 cycles, 1% duty cycle, and acoustic power from 325 to 400 W. Sonication points were placed at the center of the IVH clot. Pre- and post-treatment T1-w, T2-w, and T2*-w MR imaging was completed. Change in the clot volume was measured by segmenting the MR images. The brains were harvested and stained with hematoxylin and eosin for histological examination. Results show that LPH targeted and reduced the clot volume by 28.5-36.7% with a phase change occurring at target. H&E staining showed that visible voids were generated in the clots. Based on early data, it appears that LPH can mechanically reduce the volume of IVH clots. Future work includes increasing the study number and conducting chronic studies to determine the changes to recovery.