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

Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome

Germinal matrix-intraventricular haemorrhage (GMH-IVH), periventricular haemorrhagic infarction (PHI) and its complication, post-haemorrhagic ventricular dilatation (PHVD), are still common neonatal morbidities in preterm infants that are highly associated with adverse neurodevelopmental outcome. Typical cranial ultrasound (CUS) findings of GMH-IVH, PHI and PHVD, their anatomical substrates and underlying mechanisms are discussed in this paper. Furthermore, we propose a detailed descriptive classification of GMH-IVH and PHI that may improve quality of CUS reporting and prediction of outcome in infants suffering from GMH-IVH/PHI

Quantification of Cerebral Blood Flow and Oxidative Metabolism in Infants with Post-Hemorrhagic Ventricular Dilatation

Post-hemorrhagic ventricular dilatation (PHVD) is highly predictive of mortality and morbidity among very low birth weight preterm infants. Impaired cerebral blood flow (CBF) due to elevated intracranial pressure (ICP) is believed to be a contributing factor. In this study, a hyperspectral near-infrared spectroscopy (NIRS) method of measuring CBF and the cerebral metabolic rate of oxygen (CMRO2) was used to investigate perfusion and metabolism changes in patients receiving a ventricular tap (VT) based on clinical signs of elevated ICP. To improve measurement accuracy, the spectral analysis was modified to account for compression of the cortical mantle caused by PHVD and the possible presence of blood breakdown products. From 9 patients (27 VTs), a significant increase in CBF was measured (15.6%) following VT (14.6 ± 4.2 to 16.9 ± 6.6 ml/100g/min), but no corresponding change in CMRO2 (1.02 ± .41 ml O2/100g/min) was observed. Post-VT CBF was in good agreement with a control group of 13 patients with patent ductus arteriosus and no major cerebral pathology (16.5 ± 7.7 ml/100g/min), while StO2 was significantly lower in these patients (58.9 ± 12.1 versus 70.5 ± 9.1% for controls). This study demonstrates that PHVD impedes CBF; however, no change in CMRO2 was observed

Perfusion and Metabolic Neuromonitoring during Ventricular Taps in Infants with Post-Hemorrhagic Ventricular Dilatation.

Post-hemorrhagic ventricular dilatation (PHVD) is characterized by a build-up of cerebral spinal fluid (CSF) in the ventricles, which increases intracranial pressure and compresses brain tissue. Clinical interventions (i.e., ventricular taps, VT) work to mitigate these complications through CSF drainage; however, the timing of these procedures remains imprecise. This study presents Neonatal NeuroMonitor (NNeMo), a portable optical device that combines broadband near-infrared spectroscopy (B-NIRS) and diffuse correlation spectroscopy (DCS) to provide simultaneous assessments of cerebral blood flow (CBF), tissue saturation (

Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies

Intraventricular hemorrhage (IVH) is one of the major co-morbidities of premature birth associated with post-hemorrhagic ventricular dilatation (PHVD) development, long-term neurodevelopmental impairment, behavioral problems, special educational needs, and dependency on social security.Hypothesis and aims: We believe that extravasated blood and further release of extracellular hemoglobin (Hb) are crucial in brain injury following IVH and consequent development of PHVD. The overall goal of this project focuses on further pathogenetic insights of white and gray matter (GM) injury following IVH and the development of possible neuroprotective treatment strategies that may promote brain development in preterm infants.Methods: Paper I. We characterized extracellular Hb distribution within preriventricular white matter (WM) in preterm rabbit pups following IVH. Paper II. We evaluated the cerebral biodistribution and possible functional neuroprotection of intracerebroventricularly administered alpha-1-microglobulin (A1M), a heme and free radical scavenger, in preterm rabbit pups following IVH. Paper III. We conducted a comprehensive review of preclinical and clinical studies on WM injury following IVH. Paper IV. We evaluated high-frequency ultrasound (HFU) as a tool for the reconstruction of volumetric volume in preterm rabbit pups with PHVD and compared its accuracy and reliability with that of a gold-standard – magnetic resonance imaging (MRI). Paper V. We established a novel model of PHVD in preterm rabbit pups and characterized the survival, neurobehavior, WM, and GM injury, as well as altered corticogenesis.Results: Paper I. Following IVH extracellular Hb was widely distributed throughout the brain WM, particularly in periventricular white matter areas with high extracellular plasticity following IVH. Paper II. Exogenous A1M (recombinant) was extensively distributed within brain WM with further extension into cerebellar WM following IVH. Moreover, A1M exhibited high co-existence with extracellular Hb. Administration of A1M (human) decreased pro-inflammatory and oxidative damage. Paper III. A wide range of animal models have been used to explore pathogenetic mechanisms of IVH and related brain damage; possible targets involved in enhancing brain damage have been identified. Nevertheless, the effectiveness of potential interventions is still limited. Paper IV. HFU-based volumetric reconstruction of brain ventricles is highly accurate and reliable as compared to MRI and may be a promising bed-side tool for evaluating of progression of PHVD in preterm infants. Paper V. IVH and PHVD lead to a long-term alteration of cortical myelination microstructure, disruption of cortical organization, selectively reduction in neurogenesis and synaptogenesis, reduction in parvalbumin-positive interneurons and their dysmaturation.Conclusions: Extracellular Hb travels easily throughout brain WM following IVH and it may be one of the key factors for induction of brain damage by triggering pro-inflammatory and oxidative cascades. Furthermore, IVH, leading to PHVD, disrupts normal corticogenesis, alters myelin microstructure, causes a selective reduction in neurons, interneurons, and synapses. A1M, as a heme and free radicals scavenger, may attenuate WM damage, confirming that extracellular Hb is causative in ongoing neuroinflammation following IVH. Thus, A1M may be a possible treatment strategy in preterm infants with IVH. HFU represents a highly accurate tool for volumetric reconstruction of ventricles for diagnosis and management of PHVD

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

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

State-of-the-art neonatal cerebral ultrasound: technique and reporting

In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18\u2009MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment