MRI-Based Analysis of Intracerebral Hemorrhage in Mice Reveals Relationship between Hematoma Expansion and the Severity of Symptoms

Abstract

Intracerebral hemorrhage (ICH) is featured by poor prognosis such as high mortality rate and severe neurological dysfunction. In humans, several valuables including hematoma volume and ventricular expansion of hemorrhage are known to correlate with the extent of mortality and neurological dysfunction. However, relationship between hematoma conditions and the severity of symptoms in animal ICH models has not been clarified. Here we addressed this issue by using 7-tesla magnetic resonance imaging (MRI) on collagenase-induced ICH model in mice. We found that the mortality rate and the performance in behavioral tests did not correlate well with the volume of hematoma. In contrast, when hemorrhage invaded the internal capsule, mice exhibited high mortality and showed poor sensorimotor performance. High mortality rate and poor performance in behavioral tests were also observed when hemorrhage invaded the lateral ventricle, although worsened symptoms associated with ventricular hemorrhage were apparent only during early phase of the disease. These results clearly indicate that invasion of the internal capsule or the lateral ventricle by hematoma is a critical determinant of poor prognosis in experimental ICH model in mice as well as in human ICH patients. MRI assessment may be a powerful tool to refine investigations of pathogenic mechanisms and evaluations of drug effects in animal models of ICH.

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

“…Or is there some other, yet undetermined, factor? An MRI animal study suggests that mortality may be determined less by hematoma volume than by the invasion of internal capsule suggesting an anatomically more eloquent basis for clinical deterioration (170). Patient selection may be the key as not everyone would benefit from either surgery or medical therapy, possibly depending on damage to an eloquent area or pathway during the primary injury.…”

Does Dabigatran Increase the Risk of Delayed Hematoma Expansion in a Rat Model of Collagenase-induced Intracerebral Hemorrhage?

“…However, it should be mentioned that the measured area contained both the hematoma itself and the perihematomal edema. T2* MRI images, which clearly depict hematoma, 19 were not available in our MRI system and T2-weighted images, which may not discriminate hematoma from perihematomal edema sufficiently, were used for the analysis instead. Therefore, it may be more prudent and accurate to state that there were no significant intergroup differences in the areas depicted as hyperintensity/hypointensity on the T2-weighted images.…”

Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice

“…T2-weighted (T2wt) MRI is used to define the area of blood clot in the haemorrhagic lesion4; T1-gadolium (T1-Gd) enhancement MRI can detect the presence of blood-brain barrier (BBB) disruption5; apparent diffusion coefficient (ADC) can be used to evaluate cytotoxic and vasogenic oedema67; and diffusion tensor imaging (DTI) allows for quantitative evaluation of the structural integrity of white matter tracts, which can predict motor recovery89.…”