An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis.

Abstract

Intraventricular hemorrhage (IVH) affects approximately 50% of premature births where 50% further develop post-hemorrhagic ventricular dilation (PHVD). Patients face significant impact to long-term development if PHVD is not managed. Unfortunately, there is no accepted treatment to remove the thrombus caused by IVH. This paper describes an acute and chronic IVH model for use with magnetic resonance-guided focused ultrasound (MRgFUS) thrombolysis. A total of 12 pigs (~ 1month in age) were used in the model (eight acute and four chronic). A pre-operative brain MRI was obtained for ventricular targeting. 1.25cm3/kg of autologous blood was injected through a burr hole lateral to the midline and anterior of the coronal suture at a rate of 0.6cm3/min. A craniotomy was performed to simulate a "fontanelle". Post-operative MRI was used to calculate the clot volume. Chronic piglets were recovered, monitored daily with a neurological scoring system (NSS), and MRI scanned for 21days. The clot injection was well tolerated. The average clot size was 3987mm3 (median = 4330mm, standard deviation = 739mm3). Postmortem examination validated the presence of the clot. In the chronic animals, there was an increase in ventricular volume of 30%. Transient neurological impairment immediately followed clot injection and with onset of hydrocephalus in the chronic animals. This model establishes a measurable and targetable IVH clot in an MRI-based neonatal porcine model. The progressive post-hemorrhagic ventricular dilation in the chronic model is a potential alterable outcome from MRgFUS thrombolysis.