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Background and Purpose Despite being the gold standard technique for stroke assessment, conventional diffusion magnetic resonance imaging (dMRI) provides only partial information about tissue microstructure. Diffusional kurtosis imaging (DKI) is an advanced dMRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis (K), which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics (WMM). The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WMM. Methods We performed a retrospective review of clinical and DKI data of forty-four acute/subacute ischemic stroke patients. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. ROI analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared to the contralateral hemisphere. Results K maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient (ADC) maps. K metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WMM reveal an increase in axonal density and a larger decrease in the intra-axonal (Da) compared to extra-axonal (De) diffusion microenvironment of the ischemic WM lesion. Conclusions The well-known decrease in the ADC of WM following ischemia is found to be mainly driven by a significant drop in Da. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.

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ObjectivesMaternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood.MethodWe used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities.ResultsPolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating.ConclusionsOur results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.