Ultrasound Guidance to Replicate Transuterine BioGlue Injection in the Fetal Hydrocephalus Sheep Model.

Abstract

Introduction: Congenital hydrocephalus often results in irreversible and severe damage to the brain despite postnatal interventions. The potential for prenatal intervention to mitigate these deleterious effects underscores the importance of a suitable animal model. We aimed assess the results of an ultrasound-guided transuterine approach to replicate the BioGlue injection fetal hydrocephalus model.

Methods: Pregnant ewes were anesthetized at 95 days of gestation and BioGlue was injected into the fetal cisterna magna under ultrasound guidance through the uterus. Ventriculomegaly was assessed by MRI and histology.

Results: Nine pregnant ewes were included in the study, and their fetuses were divided into the BioGlue intervention group (n = 9 fetuses) or the control group (n = 7 fetuses) who were not injected. Although hydrocephalus was noted in 5 of 9 fetuses in the intervention group, the ability to induce hydrocephalus went from 0% to 100% in the last 3 fetuses following technical modifications. None of the controls developed hydrocephalus. Fetal brains with hydrocephalus demonstrated increased IBA1+ compared to control animals.

Conclusions: While technical challenges were noted, the ultrasound-guided transuterine approach to replicate the BioGlue fetal hydrocephalus model in sheep showed consistent and reproducible results. This model offers the advantage of directly visualizing the location of the needle tip and injection of the BioGlue. This technique offers an alternative for testing novel approaches for prenatal congenital hydrocephalus treatment.