Histopathologic correlation with diffusion tensor imaging after chronic hypoxia in the immature ferret

Abstract

Chronic hypoxia in rodents induces white matter (WM) injury similar to that in human preterm infants. We used diffusion tensor imaging (DTI) and immunohistochemistry to study the impact of hypoxia in the immature ferret at two developmental time points relevant to the preterm and term brain. On ex vivo imaging, the apparent diffusion coefficient (ADC) was decreased throughout the WM after 10 days of hypoxia (hypoxia from postnatal day 10 (P10) to P20 and killed at P20 (early hypoxia P20)), corresponding to increased astrocytosis and decreased myelination. Diffusion values normalized after 10 days of normoxia (hypoxia from P10 to P20 and killed at P30 (early hypoxia P30)), but immunohistochemistry revealed significant astrocytosis and hypomyelination. In contrast, ADC and anisotropy were increased after 10 days of hypoxia at a later developmental time point (hypoxia from P20 to P30 and killed at P30 (late hypoxia P30)), with less astrocytosis and more prominent myelination. The patterns of alteration in imaging and histology varied in relation to the developmental time at which hypoxia occurred. Normalization of diffusion measures did not correspond to the normalization of underlying histopathology. Ferrets were subjected to 10% hypoxia and divided into three groups: early hypoxia P20, early hypoxia P30, and late hypoxia P30.