Radiographic and histologic characterisation of white matter injury in a sheep model of CHD

Area of Science:

• Neuroscience
• Developmental Biology
• Medical Imaging

Background:

• Congenital heart disease (CHD) affects nearly 20% of neonates, often presenting with white matter injury (WMI) visible on MRI as T1 hyperintense lesions.
• This specific pattern of WMI is linked to adverse neurodevelopmental outcomes, yet its underlying causes and histological features remain poorly understood.

Purpose of the Study:

• To investigate the etiology and histological characteristics of T1 hyperintense white matter lesions in the context of simulated in utero conditions of CHD.
• To establish a preclinical model for studying neonatal brain injury associated with congenital heart defects.

Main Methods:

• A fetal sheep model was utilized, with cannulation at 110 days gestational age onto a pumpless extracorporeal oxygenator via umbilical vessels.
• The fetus was maintained in a fluid environment for 14.5 days under simulated hypoxic conditions (mean oxygen delivery 16 ml/kg/day) to mimic in utero CHD.
• Post-necropsy, the brain was fixed, imaged using MRI, and then histologically stained to identify and characterize areas of injury.

Main Results:

• The fetal sheep exposed to hypoxemic in utero conditions developed a T1 hyperintense lesion in the right frontal lobe, observable on MRI.
• Histological examination of the lesion revealed characteristic features of microvascular proliferation and astrocytosis, notably without evidence of gliosis.

Conclusions:

• The study successfully created a fetal model of WMI relevant to CHD, demonstrating T1 hyperintense lesions characterized by microvascular changes and astrocytosis.
• These findings provide crucial insights into the potential mechanisms driving white matter injury in neonates with congenital heart disease, paving the way for further research and potential therapeutic strategies.