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

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

Quantitative 3-D head ultrasound measurements of ventricle volume to determine thresholds for preterm neonates requiring interventional therapies following posthemorrhagic ventricle dilatation

Dilatation of the cerebral ventricles is a common condition in preterm neonates with intraventricular hemorrhage. This posthemorrhagic ventricle dilatation (PHVD) can lead to lifelong neurological impairment through ischemic injury due to increased intracranial pressure, and without treatment can lead to death. Two-dimensional ultrasound (US) through the fontanelles of the patients is serially acquired to monitor the progression of PHVD. These images are used in conjunction with clinical experience and physical exams to determine when interventional therapies such as needle aspiration of the built up cerebrospinal fluid (ventricle tap, VT) might be indicated for a patient; however, quantitative measurements of the ventricles size are often not performed. We describe the potential utility of the quantitative three-dimensional (3-D) US measurements of ventricle volumes (VVs) in 38 preterm neonates to monitor and manage PHVD. Specifically, we determined 3-D US VV thresholds for patients who received VT in comparison to patients with PHVD who resolve without intervention. In addition, since many patients who have an initial VT will receive subsequent interventions, we determined which PHVD patients will receive additional VT after the initial one has been performed. (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

Automated registration and stitching of multiple 3D ultrasound images for monitoring neonatal intraventricular hemorrhage

Dilatation of the cerebral ventricles is a common condition in preterm neonates with intraventricular hemorrhage (IVH). Post Hemorrhagic Ventricular Dilatation (PHVD) can lead to lifelong neurological impairment caused by ischemic injury due to increased intracranial pressure, and without treatment can lead to death. Previously, we have developed and validated a 3D ultrasound (US) system to monitor the progression of ventricle volumes (VV) in IVH patients; however, many patients with severe PHVD have ventricles so large they cannot be imaged within a single 3D US image. This limits the utility of atlas based segmentation algorithms required to measure VV as parts of the ventricles are in separate 3D US images, and thus, an already challenging segmentation becomes increasingly difficult to solve. Without a more automated segmentation, the clinical utility of 3D US ventricle volumes cannot be fully realized due to the large number of images and patients required to validate the technique in a clinical trials. Here, we describe the initial results of an automated ‘stitching’ algorithm used to register and combine multiple 3D US images of the ventricles of patients with PHVD. Our registration results show that we were able to register these images with an average target registration error (TRE) of 4.25±1.95 mm

Quantification of Cerebral Ventricle Volume Change of Preterm Neonates Using 3D Ultrasound Images

Intraventricular hemorrhage (IVH) is a major cause of brain injury in preterm neonates. Quantitative measurement of ventricular dilation or shrinkage is important for monitoring patients and in evaluation of treatment options. 3D ultrasound (US) has been used to monitor the ventricle volume as a biomarker for ventricular dilation. However, volumetric quantification does not provide information as to where dilation occurs. The location where dilation occurs may be related to specific neurological problems later in life. For example, posterior horn enlargement, with thinning of the corpus callosum and parietal white matter fibres, could be linked to poor visuo-spatial abilities seen in hydrocephalic children. In this work, we report on the development and application of a method used to analyze local surface change of the ventricles of preterm neonates with IVH from 3D US images. The technique is evaluated using manual segmentations from 3D US images acquired in two imaging sessions. The surfaces from baseline and follow-up were registered and then matched on a point-by-point basis. The distance between each pair of corresponding points served as an estimate of local surface change of the brain ventricle at each vertex. The measurements of local surface change were then superimposed on the ventricle surface to produce the 3D local surface change map that provide information on the spatio-temporal dilation pattern of brain ventricles following IVH. This tool can be used to monitor responses to different treatment options, and may provide important information for elucidating the deficiencies a patient will have later in life

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

Nanocapsules With Naringin And Naringenin Affect Hepatic and Renal Energy Metabolism Without Altering Serum Markers of Toxicity in Rats

Naringin and naringenin are flavonoids found in citrus fruits and have several health benefits, however these compounds are susceptible to degradation, limiting their therapeutic application. To solve this problem, an alternative is to incorporate them into nanocapsules. The aim of this work was to evaluate the toxicity of these nanocapsules against renal and hepatic serum markers and also on the activities of pyruvate kinase, Mg2+-ATPase, and creatine kinase. Nanocapsules containing naringin and naringenin, nanocapsules without the active compounds and the compounds in their free form were administered orally, once a day, for 28 days. After treatment, the serum levels of hepatic and renal markers were not altered, nor the activities of pyruvate kinase tissue, however, the treatment of nanocapsules with flavonoids increased the activities of mitochondrial creatine kinase in the kidney and hepatic Mg2+-ATPase. Thus, renal and hepatic serum markers, which are normally used as indicators of toxicity, did not change after the period of administration of the nanoparticles. However, the activities of important enzymes of the energy metabolism in these organs were affected. Our findings reinforce that nanomaterial testing for toxicity needs to go beyond traditional methods to ensure the safe use of nanoparticles for therapeutic purposes

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements