Brain segmentation in patients with perinatal arterial ischemic stroke.

BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is associated with adverse neurological outcomes. Quantification of ischemic lesions and consequent brain development in newborn infants relies on labor-intensive manual assessment of brain tissues and ischemic lesions. Hence, we propose an automatic method utilizing convolutional neural networks (CNNs) to segment brain tissues and ischemic lesions in MRI scans of infants suffering from PAIS. MATERIALS AND METHODS: This single-center retrospective study included 115 patients with PAIS that underwent MRI after the stroke onset (baseline) and after three months (follow-up). Nine baseline and 12 follow-up MRI scans were manually annotated to provide reference segmentations (white matter, gray matter, basal ganglia and thalami, brainstem, ventricles, extra-ventricular cerebrospinal fluid, and cerebellum, and additionally on the baseline scans the ischemic lesions). Two CNNs were trained to perform automatic segmentation on the baseline and follow-up MRIs, respectively. Automatic segmentations were quantitatively evaluated using the Dice coefficient (DC) and the mean surface distance (MSD). Volumetric agreement between segmentations that were manually and automatically obtained was computed. Moreover, the scan quality and automatic segmentations were qualitatively evaluated in a larger set of MRIs without manual annotation by two experts. In addition, the scan quality was qualitatively evaluated in these scans to establish its impact on the automatic segmentation performance. RESULTS: Automatic brain tissue segmentation led to a DC and MSD between 0.78-0.92 and 0.18-1.08 mm for baseline, and between 0.88-0.95 and 0.10-0.58 mm for follow-up scans, respectively. For the ischemic lesions at baseline the DC and MSD were between 0.72-0.86 and 1.23-2.18 mm, respectively. Volumetric measurements indicated limited oversegmentation of the extra-ventricular cerebrospinal fluid in both the follow-up and baseline scans, oversegmentation of the ischemic lesions in the left hemisphere, and undersegmentation of the ischemic lesions in the right hemisphere. In scans without imaging artifacts, brain tissue segmentation was graded as excellent in more than 85% and 91% of cases, respectively for the baseline and follow-up scans. For the ischemic lesions at baseline, this was in 61% of cases. CONCLUSIONS: Automatic segmentation of brain tissue and ischemic lesions in MRI scans of patients with PAIS is feasible. The method may allow evaluation of the brain development and efficacy of treatment in large datasets.

Perinatal Ischemic Stroke: Etiology and Imaging.

Perinatal ischemic stroke is a common cause of lifelong disability.

Signatures of brain plasticity supporting language recovery after perinatal arterial ischemic stroke.

Brain imaging methods such as functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI) have already been used to decipher the functional and structural brain changes occurring during normal language development. However, little is known about the differentiation of the language network after an early lesion. While in adults, stroke over the left hemisphere generally induces post-stroke aphasia, it is not always the case when a stroke occurs in the perinatal period, thus revealing a remarkable plastic power of the language network during early development. In particular, the role of perilesional tissues, as opposed to undamaged brain areas in the functional recovery of language functions after an early insult, remains unclear. In this review article, we provide an overview of the extant literature using functional and structural neuroimaging data revealing the signatures of brain plasticity underlying near-normal language development.

Perinatal stroke.

Perinatal stroke is a heterogeneous syndrome resulting from brain injury of vascular origin that occurs between 20 weeks of gestation and 28 days of postnatal life. The incidence of perinatal stroke is estimated to be between 1:1600 and 1:3000 live births (approximately 2500 children per year in the United States), though its actual incidence is difficult to estimate because it is likely underdiagnosed. Perinatal arterial ischemic stroke (PAIS) accounts for approximately 70% of cases of perinatal stroke. Cerebral sinovenous thrombosis, while less common, also accounts for a large proportion of the morbidity and mortality seen with perinatal stroke. Hemorrhagic stroke leads to disruption of neurologic function due to intracerebral hemorrhage that is nontraumatic in origin. While most cases of PAIS fall into one of these three categories, other patterns of injury should also be considered perinatal stroke. In some cases, the etiology of PAIS is not known but is idiopathic. This chapter will review the classification, risk factors, pathogenesis, clinical presentation, management, and long-term sequelae of perinatal stroke.

Right Structural and Functional Reorganization in Four-Year-Old Children with Perinatal Arterial Ischemic Stroke Predict Language Production.

Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS). Specifically, we gathered specific fine-grained developmental measures of receptive and productive aspects of language as well as standardized measures of cognitive development. We also collected structural neuroimaging data as well as functional activations during a passive listening story-telling fMRI task and a resting state session (rs-fMRI). Children with a left perinatal stroke showed larger lateralization indices of both structural and functional connectivity of the dorsal language pathway towards the right hemisphere that, in turn, were associated with better language outcomes. Importantly, the pattern of structural asymmetry was significantly more right-lateralized in children with a left perinatal brain insult than in a group of matched healthy controls. These results strongly suggest that early lesions of the left dorsal pathway and the associated perisylvian regions can induce the interhemispheric transfer of language functions to right homolog regions. This study provides combined evidence of structural and functional brain reorganization of language networks after early stroke with strong implications for neurobiological models of language development.

Incidence of Epilepsy and Associated Risk Factors in Perinatal Ischemic Stroke Survivors.

INTRODUCTION: Epilepsy is a serious and often lifelong consequence of perinatal arterial ischemic stroke (PAIS). Variable incidences and risk factors for long-term epilepsy in PAIS have been reported. To determine the incidence of epilepsy in PAIS survivors and report factors associated with the risk of developing epilepsy, a meta-analysis and systematic review of prior publications was performed. METHODS: We examined studies on perinatal or neonatal patients (≤28 days of life) with arterial ischemic strokes in which the development of epilepsy was reported. EMBASE and MEDLINE/PubMed databases were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: A meta-analysis of 10 studies revealed a summary incidence of epilepsy in PAIS patients of 27.2% (95% confidence interval 16.6% to 41.4%) over a mean study duration of 10.4 years (range 1.5 to 17). More recent studies generally reported a lower epilepsy incidence. A systematic review identified seven possible risk factors for epilepsy in PAIS patients: hippocampal volume reduction, infarct on prenatal ultrasound, a modified Alberta Stroke Program Early Computed Tomography score ≥9, family history of seizures, cerebral palsy, and initial presentation with cognitive impairment or seizures. CONCLUSIONS: About a third of children with PAIS will develop epilepsy. While seven possible risk factors have been reported, further research is warranted to confirm the strength of their association with the development of epilepsy.

Perinatal Brain Injury: Mechanisms, Prevention, and Outcomes.

Perinatal brain injury may lead to long-term morbidity and neurodevelopmental impairment. Improvements in perinatal care have resulted in the survival of more infants with perinatal brain injury. The effects of hypoxia-ischemia, inflammation, and infection during critical periods of development can lead to a common pathway of perinatal brain injury marked by neuronal excitotoxicity, cellular apoptosis, and microglial activation. Various interventions can prevent or improve the outcomes of different types of perinatal brain injury. The objective of this article is to review the mechanisms of perinatal brain injury, approaches to prevention, and outcomes among children with perinatal brain injury.

Perinatal Arterial Ischemic Stroke Is Associated to Materno-Fetal Immune Activation and Intracranial Arteritis.

The medium-size intra-cranial arteries arising from the carotid bifurcation are prone to perinatal arterial ischemic strokes (PAIS). PAIS' physiopathology needs to be better understood to develop preventive and therapeutic interventions that are currently missing. We hypothesized that materno-fetal inflammation leads to a vasculitis affecting selectively the carotidian tree and promoting a focal thrombosis and subsequent stroke. Dams were injected with saline or lipopolysaccharide (LPS) from Escherichia coli. A prothrombotic stress was applied on LPS-exposed vs. saline (S)-exposed middle cerebral arteries (MCA). Immunolabeling detected the inflammatory markers of interest. In S-exposed newborn pups, a constitutive higher density of macrophages combined to higher expressions of tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) was observed within the wall of intra- vs. extra-cranial cervicocephalic arteries. LPS-induced maternal and placental inflammatory responses mediated by IL-1ß, TNF-α and monocyte chemotactic protein 1 (MCP-1) were associated with: (i) increased density of pro-inflammatory macrophages (M1 phenotype); and (ii) pro-inflammatory orientation of the IL-1 system (IL-1ß/IL-1 receptor antagonist (IL-1Ra) ratio) within the wall of LPS-, vs. S-exposed, intra-cranial arteries susceptible to PAIS. LPS plus photothrombosis, but not sole photothrombosis, triggered ischemic strokes and subsequent motor impairments. Based on these preclinical results, the combination of pro-thrombotic stress and selective intra-cranial arteritis arising from end gestational maternal immune activation seem to play a role in the pathophysiology of human PAIS.

Cortical Sparing in Preterm Ischemic Arterial Stroke.

BACKGROUND AND PURPOSE: Residual injury after perinatal arterial ischemic stroke in the middle cerebral artery territory usually involves the loss of cortical gray matter and subcortical white matter. In this article, we describe a different pattern of residual injury after middle cerebral artery stroke in preterm-born infants, in which the cortex is spared. METHODS: Magnetic resonance imaging scans of 40 infants (12 preterm and 28 full-term infants) with a large middle cerebral artery stroke were reviewed and correlated with outcome. RESULTS: Complete sparing of the cortex with cavitation of the underlying white matter was observed in 3 preterm infants, and partial sparing was noted in another 4 late preterm-born infants. One full-term infant had partial cortical sparing, and all others showed no sparing. Overall, 86% developed a hemiplegia and 30% had a developmental quotient below 85, but this did not vary between the different types of cortical injury. CONCLUSIONS: The pattern of cortical injury after middle cerebral artery stroke changes with gestational age and may be related to maturational changes of the vascular system. Outcome did not vary between the different patterns of cortical injury.

Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke.

BACKGROUND: Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. OBJECTIVE: Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). MATERIALS AND METHODS: We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. RESULTS: Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm(3) vs. 36,995 mm(3); P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 × 10(-6) mm(2)/s vs. 611 × 10(-6) mm(2)/s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. CONCLUSION: Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis.

Thrombosis in the Neonatal Intensive Care Unit.

Neonates have the highest risk for pathologic thrombosis among pediatric patients. A combination of genetic and acquired risk factors significantly contributes to this risk, with the most important risk factor being the use of central venous catheters. Proper imaging is critical for confirming the diagnosis. Despite a significant number of these events being life- and limb-threatening, there is limited evidence on what the appropriate management strategy should be. Evaluation and treatment of any neonate with a clinically significant thrombosis should occur at a tertiary referral center that has proper support.

Knockout of vascular early response gene worsens chronic stroke outcomes in neonatal mice.

Vascular early response gene (Verge) is a novel immediate early gene that is highly expressed during developmental angiogenesis and after ischemic insults in adult brain. However, the role of Verge after neonatal injury is not known. In the present study, we investigated the hypothesis that Verge contributes to vascular remodeling and tissue repair after neonatal ischemic injury. The Rice-Vanucci model (RVM) was employed to induce neonatal stroke in both Verge knockout (KO) and wild-type (WT) postnatal day 10 (P10) mice. Histological and behavioral outcomes at acute (24h), subacute (7 days) and chronic (30 days) phases were evaluated. Angiogenesis, neurogenesis, and glial scar formation were also examined in the ischemic brain. No significant differences in outcomes were found between WT and Verge mice at 24h or 7 days after stroke. However genetic deletion of Verge led to pronounced cystic cavitation, decreased angiogenensis and glial scar formation in the ischemic hemisphere compared to WT mice at 30 days. Verge KO mice also had significantly worse functional outcomes at 30 days which was accompanied by decreased neurogenesis and angiogenesis in the ischemic hemisphere. Our study suggests that Verge plays an important role in the induction of neurogenesis and angiogenesis after ischemia, contributes to improved tissue repair, and enhances chronic functional recovery.