3D MR Ventricle Segmentation in Pre-term Infants with Post-Hemorrhagic Ventricle Dilation

Intraventricular hemorrhage (IVH) or bleed within the brain is a common condition among pre-term infants that occurs in very low birth weight preterm neonates. The prognosis is further worsened by the development of progressive ventricular dilatation, i.e., post-hemorrhagic ventricle dilation (PHVD), which occurs in 10-30% of IVH patients. In practice, predicting PHVD accurately and determining if that specific patient with ventricular dilatation requires the ability to measure accurately ventricular volume. While monitoring of PHVD in infants is typically done by repeated US and not MRI, once the patient has been treated, the follow-up over the lifetime of the patient is done by MRI. While manual segmentation is still seen as a gold standard, it is extremely time consuming, and therefore not feasible in a clinical context, and it also has a large inter-and intra-observer variability. This paper proposes an segmentation algorithm to extract the cerebral ventricles from 3D T1-weighted MR images of pre-term infants with PHVD. The proposed segmentation algorithm makes use of the convex optimization technique combined with the learned priors of image intensities and label probabilistic map, which is built from a multi-atlas registration scheme. The leave-one-out cross validation using 7 PHVD patient T1 weighted MR images showed that the proposed method yielded a mean DSC of 89.7% +/- 4.2%, a MAD of 2.6 +/- 1.1 mm, a MAXD of 17.8 +/- 6.2 mm, and a VD of 11.6% +/- 5.9%, suggesting a good agreement with manual segmentations

3D Ultrasound in the Management of Post Hemorrhagic Ventricle Dilatation

Enlargement of the cerebral ventricles is relatively common among extremely preterm neonates born before 28 weeks gestational age. One common cause of ventricle dilatation is post hemorrhagic ventricle dilatation following a bleed in the cerebral ventricles. While many neonates with PHVD will have spontaneous resolution of the condition, severe, persistent PHVD is associated with a greater risk of brain injury and morbidity later in life and left untreated can cause death. The current clinical management strategy consists of daily measurements of head circumference and qualitative interpretation of two-dimensional US images to detect ventricular enlargement and monitoring vital signs for indications increased intracranial pressure (i.e. apnea, bradycardia). Despite the widespread clinical use of these indicators, they do not have the specificity to reliably indicate when an intervention to remove some CSF is required to prevent brain damage. Early recognition of interventional necessity using quantitative measurements could help with the management of the disease, and could lead to better care in the future. Our objective was to develop and validate a three-dimensional ultrasound system for use within an incubator of neonates with PHVD in order to accurately measure the cerebral ventricle volume. This system was validated against known geometric phantoms as well as a custom ventricle-like phantom. Once validated, the system was used in a clinical study of 70 neonates with PHVD to measure the ventricle size. In addition to three-dimensional ultrasound, clinical ultrasound images, and MRIs were attained. Clinical measurements of the ventricles and three-dimensional ultrasound ventricle volumes were used to determine thresholds between neonates with PHVD who did and did not receive interventions based on current clinical management. We determined image based thresholds for intervention for both neonates who will receive an initial intervention, as well as those who will receive multiple interventions. Three-dimensional ultrasound based ventricle volume measurements had high sensitivity and specificity as patients with persistent PHVD have ventricles that increase in size faster than those who undergo resolution. This allowed for delineation between interventional and non-interventional patients within the first week of life. While this is still a small sample size study, these results can give rise to larger studies that would be able to determine if earlier intervention can result in better neurodevelopmental outcomes later in life

Clinical application of 3D ultrasound in neonatal intraventricular hemorrhage

Preterm neonates are at risk for intraventricular hemorrhage (IVH) and subsequent post-hemorrhagic hydrocephalus (PHH). A well-accepted interventional therapy for PHH is ventricular tap (VT). Permanent treatment, ventriculo peritoneal shunt surgery (VPS) is required in the case of some neonates under some conditions (weight, immunological status, CSF protein level) who receive multiple interventions. The objective of this study was to apply a 3D ultrasound system clinically to determine CSF volume within the ventricle, to guide the neurosurgeon regarding the amount of CSF should be removed during every intervention, which lateral ventricle is better to intervene and to predict the possibilities of the requirement of the shunt. After ethics approval and parental consent, this 3D US system was used in a clinical study where data of 70 neonates having IVH were analyzed retrospectively and 22 preterm neonates were recruited prospectively. 3D US system was used to measure the ventricle volume of the neonates. In addition, we have changed the posture of some neonates to find the volume variation in two lateral postures. We found that 3D US ventricle volume had a higher correlation (Pearson correlation 0.739) with the amount of CSF removed in each tap than other parameters (weight, age, head circumference). After changing the posture of the neonates, we did not find any significant volume change of two lateral ventricle volumes (P-value was 0.353 in case of the right ventricle in two different postures and 0.473 in case of the left ventricle in two different postures). We also found more volume change after VT in those patients who required VPS than who did not need a VPS (volume change was18.70 ± 10.98 cm3 in shunt treated patients and 7.52 ± 3.35 cm3 in patients with no shunt where P- value was 0.0001). Therefore, our study suggests that a volumetric measurement of total lateral ventricles by the 3D US could be used concurrently with other physical parameters for better management of the neonates having PHH

Preterm neonatal lateral ventricle volume from three-dimensional ultrasound is not strongly correlated to two-dimensional ultrasound measurements

The aim of this study is to compare longitudinal two-dimensional (2-D) and three-dimensional (3-D) ultrasound (US) estimates of ventricle size in preterm neonates with posthemorrhagic ventricular dilatation (PHVD) using quantitative measurements of the lateral ventricles. Cranial 2-D US and 3-D US images were acquired from neonatal patients with diagnosed PHVD within 10 min of each other one to two times per week and analyzed offline. Ventricle index, anterior horn width, third ventricle width, and thalamo-occipital distance were measured on the 2-D images and ventricle volume (VV) was measured from 3-D US images. Changes in the measurements between successive image sets were also recorded. No strong correlations were found between VV and 2-D US measurements (R-2 between 0.69 and 0.36). Additionally, weak correlations were found between changes in 2-D US measurements and 3-D US VV (R-2 between 0.13 and 0.02). A trend was found between increasing 2-D US measurements and 3-D US-based VV, but this was not the case when comparing changes between 3-D US VV and 2-D US measurements. If 3-D US-based VV provides a more accurate estimate of ventricle size than 2-D US measurements, moderate-weak correlations with 3-D US suggest that monitoring preterm patients with PHVD using 2-D US measurements alone might not accurately represent whether the ventricles are progressively dilating. A volumetric measure (3-D US or MRI) could be used instead to more accurately represent changes. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI

Advanced MR brain imaging in preterm infants

The aim of the thesis is to investigate the diagnostic value of MRI performed around term equivalent age in evaluating brain injury and predicting neurodevelopmental outcome at two years corrected age in very preterm infants with a gestational age of less than 32 weeks. MRI is a powerful tool to diagnose all types of white matter injury and is more sensitive than ultrasound in detecting punctate white matter lesions which are associated with developmental delay and cerebral palsy. The positive predictive value of specific MRI findings such as punctate white matter lesions, and also cystic lesions and ventricular dilatation for cognitive and motor delay is low. Advanced DTI techniques are promising and may help predicting clinical outcome. However in combination with findings on conventional MRI sequences, there is only a slight increase in sensitivity and specificity. At this stage a routine clinical MRI in every preterm infant does not seem warranted. In the future, serial MRI and the application of advanced techniques may provide insights into brain development and injury to the preterm infant__s brain, and they may help predicting neurological outcome.UBL - phd migration 201

MR Elastography demonstrates reduced white matter shear stiffness in early-onset hydrocephalus

INTRODUCTION: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures. METHODS: MRE was collected at two imaging sites in 39 hydrocephalus patients and 33 healthy controls, along with demographic, shunt-related, and clinical outcome measures including headache and quality of life indices. Brain stiffness was quantified for whole brain, global white matter (WM), and lobar WM stiffness. Group differences in brain stiffness between patients and controls were compared using two-sample t-tests and multivariable linear regression to adjust for age, sex, and ventricular volume. Among patients, multivariable linear or logistic regression was used to assess which factors (age, sex, ventricular volume, age at first shunt, number of shunt revisions) were associated with brain stiffness and whether brain stiffness predicts clinical outcomes (quality of life, headache and depression). RESULTS: Brain stiffness was significantly reduced in patients compared to controls, both unadjusted (p ≤ 0.002) and adjusted (p ≤ 0.03) for covariates. Among hydrocephalic patients, lower stiffness was associated with older age in temporal and parietal WM and whole brain (WB) (beta (SE): -7.6 (2.5), p = 0.004; -9.5 (2.2), p = 0.0002; -3.7 (1.8), p = 0.046), being female in global and frontal WM and WB (beta (SE): -75.6 (25.5), p = 0.01; -66.0 (32.4), p = 0.05; -73.2 (25.3), p = 0.01), larger ventricular volume in global, and occipital WM (beta (SE): -11.5 (3.4), p = 0.002; -18.9 (5.4), p = 0.0014). Lower brain stiffness also predicted worse quality of life and a higher likelihood of depression, controlling for all other factors. CONCLUSIONS: Brain stiffness is reduced in hydrocephalus patients compared to healthy controls, and is associated with clinically-relevant functional outcome measures. MRE may emerge as a clinically-relevant biomarker to assess the neuropathological effects of hydrocephalus and shunting, and may be useful in evaluating the effects of therapeutic alternatives, or as a supplement, of shunting

Volumetric and symmetry comparison of intracranial matter between preterm and full-term children

BACKGROUND: Pre-term delivery is known to cause developmental problems due to the fragile nature of the premature brain. In particular, ventriculomegaly is a commonly observed phenomenon due to the hemorrhaging of the germinal matrix, and may cause alterations in the volumes of gray matter, white matter and cerebrospinal fluid in growing pre-term children. METHODS: The volume and symmetry of a sample population of ELGAN (Extremely Low Gestational Age Newborns) and normal-term population obtained from the NIH Study of Normal Brain Development was evaluated. The ELGAN group consisted of 88 subjects from age group 9 to 11 and the normal-term group consisted of 68 subjects from age group 7 to 11. Magnetic resonance images were taken from both samples and the intracranial matter was measured and segmented. RESULTS: Histograms of the obtained volumes showed a normal distribution and statistical analysis for each sample group and gender. The ELGAN group had higher intracranial volumes and showed statistically significant asymmetry that was not present in the normal term population with a larger right brain than left brain. Discussion: Results indicate that preterm delivery may alter processes that allow for symmetrical brain development and heavily favor the relative higher expansion of the right side of the brain. CONCLUSION: Further analysis of the concentration and location of the white matter and gray matter in both preterm and normal term children is necessary in order to understand the adaptive mechanisms that may be activated in order to offset the damage done to the premature brain