Progression of brain lesions in relation to hyperperfusion from subacute to chronic stages after experimental...

The pathogenesis of delayed cerebral injury after aneurysmal subarachnoid hemorrhage (SAH) is largely unresolved. In particular, the progression and interplay of tissue and perfusion changes, which can significantly affect the outcome, remain unclear. Only a few studies have assessed pathophysiological developments between subacute and chronic time points after SAH, which may be ideally studied with noninvasive methods in standardized animal models. Therefore, our objective was to characterize the pattern and correlation of brain perfusion and lesion status with serial multiparametric magnetic resonance imaging (MRI) from subacute to chronical after experimental SAH in rats.

SAH was induced by endovascular puncture of the intracranial bifurcation of the right internal carotid artery in adult male Wistar rats (n = 30). Diffusion-, T2-, perfusion- and contrast-enhanced T1-weighted MRI were performed on a 4.7-tesla animal MR system to measure cytotoxic and vasogenic edema, hemodynamic parameters and blood-brain barrier permeability, respectively, at days 2 and 7 after SAH. The neurological status was repeatedly monitored with different behavioral tests between days -1 and 7 after SAH. Lesioned tissue - identified by edema-associated T2 prolongation - and unaffected tissue were outlined on multislice images and further characterized based on tissue and perfusion indices. Correlation analyses were performed to evaluate relationships between different MRI-based parameters and between MRI-based parameters and neurological scores.

Similar to clinical SAH and previous studies in this experimental SAH model, mortality up to day 2 was high (43%). In surviving animals, neurological function was significantly impaired subacutely, and tissue damage (characterized by T2 prolongation and diffusion reduction) and blood-brain barrier leakage (characterized by contrast agent extravasation) were apparent in ipsilateral cortical and subcortical tissue as well as in contralateral cortical tissue. Notably, ipsilateral cortical areas revealed increased cerebral blood flow and volume. Animals that subsequently died between days 2 and 7 after SAH had markedly elevated ipsilateral perfusion levels at day 2. After a week, neurological function had improved in surviving animals, and brain edema was partially resolved, while blood-brain barrier permeability and hyperperfusion persisted. The degree of brain damage correlated significantly with the level of perfusion elevation (r = 0.78 and 0.85 at days 2 and 7, respectively; p < 0.05). Furthermore, chronic (day 7 after SAH) blood-brain barrier permeability and vasogenic edema formation were associated with subacute (day 2 after SAH) hyperperfusion (r = 0.53 and 0.66, respectively; p < 0.05).

Our imaging findings indicate that SAH-induced brain injury at later stages is associated with progressive changes in tissue perfusion and that chronic hyperperfusion may contribute or point to delayed cerebral damage. Furthermore, multiparametric MRI may significantly aid in diagnosing the brain's status after SAH.