Neonatal Cerebral Sinovenous Thrombosis:Neuroimaging and Long-term Follow-up

Neonates are known to have a higher risk of cerebral sinovenous thrombosis than children of other age groups. The exact incidence in neonates remains unknown and is likely to be underestimated, as clinical presentation is nonspecific and diagnosis can only be made when dedicated neuroimaging techniques, including computed tomographic venography or magnetic resonance venography, are performed. Associated intracranial lesions are common and some, such as a unilateral thalamic hemorrhage, should suggest cerebral sinovenous thrombosis as the underlying etiology. Neurodevelopmental outcome is poor in approximately 50% of these infants and is adversely affected by associated parenchymal lesions. Anticoagulation therapy will limit propagation of the clot and possibly the development or enhancement of parenchymal lesions. Multicenter randomized clinical trials are urgently needed to address many of these important issues

Automatic segmentation of the preterm neonatal brain with MRI using supervised classification

Cortical folding ensues around 13-14 weeks gestational age and a qualitative analysis of the cortex around this period is required to observe and better understand the folds arousal. A quantitative assessment of cortical folding can be based on the cortical surface area, extracted from segmentations of unmyelinated white matter (UWM), cortical grey matter (CoGM) and cerebrospinal uid in the extracerebral space (CSF). This work presents a method for automatic segmentation of these tissue types in preterm infants. A set of T1- and T2-weighted images of ten infants scanned at 30 weeks postmenstrual age was used. The reference standard was obtained by manual expert segmentation. The method employs supervised pixel classification in three subsequent stages. The classification is performed based on the set of spatial and texture features. Segmentation results are evaluated in terms of Dice coefficient (DC), Hausdorff distance (HD), and modified Hausdorff distance (MHD) defined as 95th percentile of the HD. The method achieved average DC of 0.94 for UWM, 0.73 for CoGM and 0.86 for CSF. The average HD and MHD were 6.89 mm and 0.34 mm for UWM, 6.49 mm and 0.82 mm for CoGM, and 7.09 mm and 0.79 mm for CSF, respectively. The presented method can provide volumetric measurements of the segmented tissues, and it enables quantification of cortical characteristics. Therefore, the method provides a basis for evaluation of clinical relevance of these biomarkers in the given population. © 2013 SPIE

Automatic segmentation of the preterm neonatal brain with MRI using supervised classification

Cortical folding ensues around 13-14 weeks gestational age and a qualitative analysis of the cortex around this period is required to observe and better understand the folds arousal. A quantitative assessment of cortical folding can be based on the cortical surface area, extracted from segmentations of unmyelinated white matter (UWM), cortical grey matter (CoGM) and cerebrospinal uid in the extracerebral space (CSF). This work presents a method for automatic segmentation of these tissue types in preterm infants. A set of T1- and T2-weighted images of ten infants scanned at 30 weeks postmenstrual age was used. The reference standard was obtained by manual expert segmentation. The method employs supervised pixel classification in three subsequent stages. The classification is performed based on the set of spatial and texture features. Segmentation results are evaluated in terms of Dice coefficient (DC), Hausdorff distance (HD), and modified Hausdorff distance (MHD) defined as 95th percentile of the HD. The method achieved average DC of 0.94 for UWM, 0.73 for CoGM and 0.86 for CSF. The average HD and MHD were 6.89 mm and 0.34 mm for UWM, 6.49 mm and 0.82 mm for CoGM, and 7.09 mm and 0.79 mm for CSF, respectively. The presented method can provide volumetric measurements of the segmented tissues, and it enables quantification of cortical characteristics. Therefore, the method provides a basis for evaluation of clinical relevance of these biomarkers in the given population. © 2013 SPIE

Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants

OBJECTIVES: To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. STUDY DESIGN: Preterm infants (gestational age <28 weeks) underwent brain magnetic resonance imaging (MRI) at around 30 weeks postmenstrual age and again around term equivalent age. MRIs were segmented in 50 different regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. RESULTS: MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. CONCLUSION: This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period

Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants

OBJECTIVES: To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. STUDY DESIGN: Preterm infants (gestational age <28 weeks) underwent brain magnetic resonance imaging (MRI) at around 30 weeks postmenstrual age and again around term equivalent age. MRIs were segmented in 50 different regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. RESULTS: MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. CONCLUSION: This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period

Development of cortical morphology evaluated with longitudinal MR brain images of preterm infants

Introduction: The cerebral cortex develops rapidly in the last trimester of pregnancy. In preterm infants, brain development is very vulnerable because of their often complicated extra-uterine conditions. The aim of this study was to quantitatively describe cortical development in a cohort of 85 preterm infants with and without brain injury imaged at 30 and 40 weeks postmenstrual age (PMA). Methods: In the acquired T2-weighted MR images, unmyelinated white matter (UWM), cortical grey matter (CoGM), and cerebrospinal fluid in the extracerebral space (CSF) were automatically segmented. Based on these segmentations, cortical descriptors evaluating volume, surface area, thickness, gyrification index, and global mean curvature were computed at both time points, for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes separately. Additionally, visual scoring of brain abnormality was performed using a conventional scoring system at 40 weeks PMA. Results: The evaluated descriptors showed larger change in the occipital lobes than in the other lobes. Moreover, the cortical descriptors showed an association with the abnormality scores: gyrification index and global mean curvature decreased, whereas, interestingly, median cortical thickness increased with increasing abnormality score. This was more pronounced at 40 weeks PMA than at 30 weeks PMA, suggesting that the period between 30 and 40 weeks PMA might provide a window of opportunity for intervention to prevent delay in cortical development

MRI Based Preterm White Matter Injury Classification : The Importance of Sequential Imaging in Determining Severity of Injury

BACKGROUND: The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings. METHODS: Eighty-two preterm infants (gestation ≤35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI. RESULTS: 138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2-6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic-WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed ≥2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami. CONCLUSION: In infants with extensive WM cysts at 2-6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI

On development of functional brain connectivity in the young brain

Our brain is a complex network of structurally and functionally interconnected regions, shaped to efficiently process and integrate information. The development from a brain equipped with basic functionalities to an efficient network facilitating complex behavior starts during gestation and continues into adulthood. Resting-state functional MRI(rs-fMRI) enables the examination of developmental aspects of functional connectivity (FC) and functional brain networks. This review will discuss changes observed in the developing brain on the level of network FC from a gestational age of 20 weeks onwards. We discuss findings of resting-state fMRI studies showing that functional network development starts during gestation, creating a foundation for each of the resting-state networks (RSNs) to be established. Visual and sensorimotor areas are reported to develop first, with other networks, at different rates, increasing both in network connectivity and size over time. Reaching childhood, marked fine-tuning and specialization takes place in the regions necessary for higher-order cognitive functions

Anticoagulation Therapy and Imaging in Neonates With a Unilateral Thalamic Hemorrhage Due to Cerebral Sinovenous Thrombosis

Background and Purpose-Cerebral sinovenous thrombosis is a rare disorder with a high risk of an adverse neurodevelopmental outcome. Until now, anticoagulation therapy has been restricted to neonates without an associated parenchymal hemorrhage. In this study, we describe sequential neuroimaging findings and use of anticoagulation therapy in newborn infants with a unilateral thalamic hemorrhage due to cerebral sinovenous thrombosis. Methods-Ten neonates with a unilateral thalamic hemorrhage and cerebral sinovenous thrombosis were studied. Diagnosis was suspected using cranial ultrasound and confirmed with MRI/MR venography. Eight infants had a repeat MRI at 3 to 7 months. Neurodevelopmental outcome was assessed from 3 months until 5 years. Results-One infant died. Seven infants were treated with low-molecular-weight heparin. No side affects were noted. MRI showed involvement of multiple sinuses, additional intraventricular hemorrhage, and white matter lesions in all infants. Recanalization was present on the repeat MRI at 3 months in all infants. Treatment was delayed in one infant and anticoagulation was started only after extension of the thalamic hemorrhage. He required a ventriculoperitoneal drain for posthemorrhagic ventricular dilatation and developed cerebral visual impairment and global delay. Two other infants showed global delay and one of them also developed postneonatal epilepsy. Mild asymmetry in tone was present in 4 children. Conclusions-Cerebral sinovenous thrombosis was found in 10 neonates with unilateral thalamic hemorrhage. Diagnosis was suspected on cranial ultrasound and confirmed with MRI/MR venography. Treatment with low-molecular-weight heparin in newborn infants with a thalamic hemorrhage due to cerebral sinovenous thrombosis appears to be safe and should be considered. Long-term follow-up will be needed to assess cognitive outcome. (Stroke. 2009; 40: 2754-2760.