Magnetic resonance imaging of ischemic injury produced by varying severities of photothrombosis differs in neonatal and adult brain

Abstract

Stroke is a major cause of disability in adults and children. Recently, we have developed an adult rat model of minor stroke containing a peri-infarct region with a modest T₂ increase and mild ischemic damage. We hypothesized that a neonatal minor stroke with mild peri-ischemic changes could also be produced, but with potential ontogenic differences. Using our minor photothrombosis method, we produced a range of severities of ischemic lesions (mini, minor, moderate and severe) within magnetic resonance imaging (MRI) slices of adult and neonatal rats. In both age groups, the lesion region showed a marked increase in T₂ and diffusion-weighted intensity and decrease in apparent diffusion coefficient (ADC), corresponding to a cortical infarct detected using fluorojade and hematoxylin and eosin staining. Perilesional regions showed modest increases in T₂ and ADC in adults, but not neonates, and this corresponded to scattered cell death, but not necessarily extravasation of plasma protein, i.e. blood-brain barrier disruption. Mini and minor insults in neonates generally showed homogeneous and rather modest changes in T₂ and ADC. MR perfusion maps demonstrated a penumbral area of greater hypoperfusion in adults compared with neonates. Together, the results indicate that, in neonatal cortex, a similar severity of photothrombosis occurs throughout the area of photoactivation, whereas, in adult brain, spontaneous clot lysis and/or partial thrombosis occurs adjacent to permanently occluded vessels. Thus, by comparing differing severities of photothrombotic ischemia in neonates and adults, ontogenic differences were detectable using MRI, with mature brain having a greater penumbral region. Mild ischemic injury and scattered cell death in both neonates and adults could be identified by a modest increase in T₂ and decrease in ADC. A better understanding of the effects of development on ischemic responses and associated MRI changes will provide a basis for the improved diagnosis of mild or minor ischemic insults relevant to pediatric and adult stroke.

Keywords: T2; animal model study; brain ischemia and degeneration; diffusion; fetal and pediatric neurological diseases.