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Many studies have explored the possibility of using cranial ultrasound for discerning intracranial pathologies like tumors, hemorrhagic stroke, or subdural hemorrhage in clinical scenarios where computer tomography may not be accessible or feasible. The visualization of intracranial anatomy on B-mode ultrasound is challenging due to the presence of the skull that limits insonation to a few segments on the temporal bone that are thin enough to allow transcranial transmission of sound. Several artifacts are produced by hyperechoic signals inherent in brain and skull anatomy when images are created using temporal windows.While the literature has investigated the accuracy of diagnosis of intracranial pathology with ultrasound, we lack a reference source for images acquired on cranial topography on B-mode ultrasound to illustrate the appearance of normal and abnormal structures of the brain and skull. Two investigators underwent hands-on training in Cranial point-of-care ultrasound (c-POCUS) and acquired multiple images from each patient to obtain the most in-depth images of brain to investigate all visible anatomical structures and pathology within 24 hours of any CT/MRI imaging done.Most reproducible structures visible on c-POCUS included bony parts and parenchymal structures. Transcranial and abdominal presets were equivalent in elucidating anatomical structures. Brain pathology like parenchymal hemorrhage, cerebral edema, and hydrocephalus were also visualized.We present an illustrated anatomical atlas of cranial ultrasound B-mode images acquired in various pathologies in a critical care environment and compare our findings with published literature by performing a scoping review of literature on the subject.

Ultrasound (US) can be used to evaluate the brain structure and nervous system damage. Patients with neurologic symptoms need rapid, noninvasive imaging with high spatial resolution and tissue contrast. Magnetic resonance imaging is currently the most sensitive and specific imaging method for evaluating neuropathologic conditions. This approach does present some challenges, such as the need to transport patients who may be seriously ill to the magnetic resonance imaging suite and the need for patients to remain for a considerable time. Cranial US provides a very valuable imaging method for clinicians, which can make a rapid diagnosis and evaluation without ionizing radiation. The main disadvantage of cranial US is its low sensitivity and specificity for subtle/early lesions. In recent years, with the rapid development of anatomic and functional US technology, the practicability of US diagnosis and intervention has been greatly improved. Ultrasound elastography may have the potential to improve the sensitivity and specificity of various cranial nerve conditions. Ultrasound elastography has received considerable critical attention, and an increasing number of studies have recognized its critical role in evaluating brain diseases. At present, US elastography has been applied to the evaluation of traumatic brain injury, ischemic stroke, intraoperative brain tumors, and hypoxic ischemic encephalopathy. The latest animal experiments and human clinical trial developments in the applications of US elastography for brain diseases are summarized in this review.

Congenital lymphocytic choriomeningitis virus (LCMV) infection is a transient intrauterine viral infection with selective teratogenicity depending on the timing of the primary maternal infection. LCMV is cleared from the body of the fetus after the acute phase of illness and, in most cases, has lost its virulence at the time of birth. LCMV competes with extracellular matrix proteins for its tropism toward heavily glycosylated alpha-dystroglycan. In the first trimester, while tropism toward heart myoblasts is high, intrauterine infection (IUI) can lead to miscarriage or fetal demise. Later in pregnancy, LCMV becomes neurotropic with tropism toward retina and brain. Most often systemic symptoms are subtle or absent at the time of birth. The timing of the IUI determines the neuroteratogenic phenotypes of congenital LCMV infection. IUI that occurs early during gestation can lead to isolated cerebellar dysgenesis and hypoplasia. When IUI occurs during neural radial migration, echoencephalography shows defective cerebral opercularization, intracranial calcifications at the gray-white matter junction, enlarged extra-axial subarachnoid space, and cortical dysplasia. When IUI occurs after the completion of insular opercularization (late second trimester), echoencephalography shows extensive cystic periventricular leukomalacia with bi-occipital porencephaly and mild defects in gyrogenesis. A late gestation IUI induces aseptic LCMV meningitis with occlusion of the aqueduct of Sylvius, leading to congenital obstructive hydrocephalus. Congenital LCMV remains underdiagnosed as clinical manifestations are predominantly neurologic. As echoencephalography remains the preferred screening strategy for detecting neonatal central nervous system pathology, prior knowledge of echoencephalography of congenital LCMV may facilitate its recognition, prompting a serological evaluation.

Objectives Brain injury in preterm neonates may cause clinical deterioration and requires timeous bedside diagnosis. Teaching cranial ultrasound (US) skills using fragile preterm neonates is challenging. The purpose of this study was to test the effectiveness and feasibility of using task-trainer computer-based simulators and US-suitable cranial phantoms in combination with teaching sessions in teaching novices to perform focused cranial US evaluations for identifying substantial intraventricular hemorrhage. Methods This was a prospective interventional educational study targeting participants with no prior skills in neonatal cranial US. Participants attended a 2-day training workshop, with didactic and hands-on interactive sessions using computer-based and 3-dimensional printed phantom simulators. Participants then performed a cranial US scan on a healthy neonate to assess the diagnostic quality of the images acquired. Individual precourse and postcourse knowledge tests were compared. To test recall, participants also submitted US images acquired on neonates within 3 and 6 months of attending the course. Results Forty-five participants completed the training modules. Mean knowledge scores increased significantly (in brain anatomy, brain physiology, intracranial disorders, and US physics domains). Thirty-eight cranial US scans were acquired during the course, 22 within 3 months after completion, and 34 within 6 months after completion. Thirty-two (84%) of the initial 38 case images, 17 (77%) of 22 images submitted within 3 months, and 32 (94%) of 34 images submitted within 6 months after course completion were of diagnostic quality. Conclusions A structured training module with didactic and hand-on training sessions using simulators and phantoms is feasible and supports training of clinicians to perform focused cranial US examinations.

Objective: Prediction of post–hemorrhagic hydrocephalus (PHH) outcome—i.e., whether it requires intervention or not—in premature neonates using cranial ultrasound (CUS) images is challenging. In this paper, we present a novel fully-automatic method to perform phenotyping of the brain lateral ventricles and predict PHH outcome from CUS. Methods: Our method consists of two parts: ventricle quantification followed by prediction of PHH outcome. First, cranial bounding box and brain interhemispheric fissure are detected to determine the anatomical position of ventricles and correct the cranium rotation. Then, lateral ventricles are extracted using a new deep learning-based method by incorporating the convolutional neural network into a probabilistic atlas-based weighted loss function and an image-specific adaption. PHH outcome is predicted using a support vector machine classifier trained using ventricular morphological phenotypes and clinical information. Results: Experiments demonstrated that our method achieves accurate ventricle segmentation results with an average Dice similarity coefficient of 0.86, as well as very good PHH outcome prediction with accuracy of 0.91. Conclusion: Automatic CUS-based ventricular phenotyping in premature newborns could objectively and accurately predict the progression to severe PHH. Significance: Early prediction of severe PHH development in premature newborns could potentially advance criteria for diagnosis and offer an opportunity for early interventions to improve outcome.

Intraventricular hemorrhage in the setting of prematurity remains the most common cause of acquired hydrocephalus. Neonates with progressive post-hemorrhagic hydrocephalus are at risk for adverse neurodevelopmental outcomes. The goal of this review is to describe the distinct and often overlapping types of brain injury in the preterm neonate, with a focus on neonatal hydrocephalus, and to connect injury on imaging to neurodevelopmental outcome risk. Head ultrasound and magnetic resonance imaging findings are described separately. The current state of the literature is imprecise and we end the review with recommendations for future radiologic and neurodevelopmental research.

The goals of treating a cerebral metastasis (CM) are to achieve local control of the disease and to improve patient quality of life. The aim of this study was to analyze the effect of conventional surgery supported by intraoperative ultrasound (IOUS) to approach a CM. To perform this analysis, we determined the postoperative Karnofsky Performance Status Scale (KPS) scores and tumor resection grades.Patients with a CM diagnosis were included in this study. Surgical treatment was either supported or not by IOUS. Pre- and postoperative KPS scores were determined by the oncology team, and cerebral tumor volume was estimated through pre- and postoperative magnetic resonance imaging. The surgical team determined whether it was possible to perform a total CM resection.There were 78 patients treated using surgical management (35 with and 43 without IOUS). In the IOUS group, the postoperative KPS scores were higher (80 vs. 70, respectively; P = 0.045) and the KPS evolution was superior (P = 0.036), especially in the following subgroups: difficulty of tumor resection ranking score4 (P = 0.037), tumor in an eloquent area (P = 0.043), tumor not associated with vessels or nerves (P = 0.007), and solitary lesions (P = 0.038). The residual tumor volume was lower in the IOUS group (9.5% and 1.6 mmIOUS may improve postoperative KPS scores and decrease residual tumor volumes in CM surgeries. These findings should be confirmed in future studies.

Background Surgery for cranial and spinal tumors has evolved tremendously over the years. Not only have neuro-oncologists been able to better understand tumor biology and thereby improve multimodality therapy, but advances in surgical techniques have also directly equipped neurosurgeons with the armamentarium necessary to achieve more radical resections safely. Intraoperative imaging tools are one such adjunct. Though intraoperative magnetic resonance (MR) has emerged as the "gold standard" among these, logistical challenges make it difficult to implement across all centers. On the other hand, the use of ultrasound (US) intraoperatively predates the use of MR. Over the past 4 decades, technologic improvements have refined and expanded the scope and application of intraoperative US technology. Strategies to maximize its efficacy and overcome the various limitations have evolved. A large volume of clinical experience has accumulated with respect to its role as an adjunct specifically in tumor surgery. Methods We performed a literature review to evaluate the role of IOUS in tumor surgery. This review traces the evolution of intraoperative US over the years and reviews the current scope and applications with respect to neuro-oncologic surgery, as well as potential future applications. Results IOUS has evolved over the years since its introduction. Advances in technology have provided real-time navigated and 3-D techniques, which overcome many of the limitations of older IOUS techniques. This has shown to be very useful in not only localization of lesions, but also in improving resection rates as well as survival. Conclusions IOUS is a powerful and versatile multipurpose intraoperative adjunct in tumor surgery, especially for resection control. The learning curve is relatively easy to climb and future improvements in technology are likely to widen the scope of its use.

To evaluate the clinical impact of routine term-equivalent magnetic resonance imaging (TE-MRI) for extremely low-birth-weight infants at a regional neonatal intensive care unit.This is a single-center retrospective study evaluating preterm survivors who underwent TE-MRI. MRI abnormalities were compared between infants with and without cranial ultrasonography (CUS) abnormalities. Cost analysis comparing imaging modalities was also performed.TE-MRI use increased from 17% in 2006 to 76% in 2010. MRI detected new findings in nearly half of infants, whether or not they had known ultrasound abnormalities. MRI detected more cerebellar (18% vs 6%, P=0.04) and moderate white matter injury (12% vs 7%, P0.001), and altered simulated neurological prognosis across developmental domains. The cost of TE-MRI was $1600, which was comparable to serial CUSs.TE-MRI detects new abnormalities and impacts developmental prognosis in the extremely low birth weight, which supports its use despite the added financial cost.

Background Surgical resection of intra-axial tumors is a challenging procedure because of indistinct tumor margins, infiltration, and displacement of white matter tracts surrounding the lesion. Hence, gross total tumor resection without causing new neurologic deficits is demanding, especially in tumor sites adjoining eloquent structures. Feasibility of the combination of navigated probabilistic fiber tracking to identify eloquent fiber pathways and navigated ultrasonography to control brain shift was tested. Methods Eleven patients with lesions adjacent to eloquent white matter structures (pyramidal tract, optic radiation and arcuate fascicle) were preoperatively subjected to magnetic resonance imaging including diffusion-weighted imaging on a 3-T magnetic resonance system (Trio [Siemens, Erlangen, Germany]). Probabilistic fiber tracking was performed using the tools of the FMRIB Software Library (FSL). Results of probabilistic fiber tracking and high-resolution anatomic images were integrated into the neuronavigation system Stealth Station (Medtronic, Minneapolis, Minnesota, USA) together with the navigated ultrasonography (SonoNav [Medtronic]). Results FSL-based probabilistic fiber tracking depicted the pyramidal tract, the optic radiation, and arcuate fascicle anatomically plausibly. Integration of the probabilistic fiber tracking into neuronavigation was technically feasible and allowed visualization of the reconstructed fiber pathways. Navigated ultrasonography controlled brain shift. Conclusions Integration of probabilistic fiber tracking and navigated ultrasonography into intraoperative neuronavigation facilitated anatomic orientation during glioma resection. FSL-based probabilistic fiber tracking integrated sophisticated fiber tracking algorithms, including modeling of crossing fibers. Combination with navigated ultrasonography provided a three-dimensional estimation of intraoperative brain shift and, therefore, improved the reliability of neuronavigation.

Reliable intraoperative resection control during surgery of malignant brain tumours is associated with the longer overall survival of patients. B-mode ultrasound (BUS) is a familiar intraoperative imaging application in neurosurgical procedures and supplies excellent image quality. However, due to resection-induced artefacts, its ability to distinguish between tumour borders, oedema, surrounding tissue and tumour remnants is sometimes limited. In experienced hands, this “bright rim effect” could be reduced. However, it should be determined, if contrast-enhanced ultrasound can improve this situation by providing high-quality imaging during the resection. The aim of this clinical study was to examine contrast-enhanced and three-dimensional reconstructed ultrasound (3D CEUS) in brain tumour surgery regarding the uptake of contrast agent pre- and post-tumour resection, imaging quality and in comparison with postoperative magnetic resonance imaging in different tumour entities. Fifty patients, suffering from various brain tumours intra-axial and extra-axial, who had all undergone surgery with the support of neuronavigation in our neurosurgical department, were included in the study. Their median age was 56 years (range, 28–79). Ultrasound imaging was performed before the Dura was opened and for resection control at the end of tumour resection as defined by the neurosurgeon. A high-end ultrasound (US) device (Toshiba Aplio XG®) with linear and sector probes for B-mode and CEUS was used. Navigation and 3D reconstruction were performed with a LOCALITE SonoNavigator® and the images were transferred digitally (DVI) to the navigation system. The contrast agent consists of echoic micro-bubbles showing tumour vascularisation. The ultrasound images were compared with the corresponding postoperative MR data in order to determine the accuracy and imaging quality of the tumours and tumour remnants after resection. Different types of tumours were investigated. High, dynamic contrast agent uptake was observed in 19 of 21 patients (90 %) suffering from glioblastoma, while in 2 patients uptake was low and insufficient. In 52.4 % of glioblastoma and grade III astrocytoma patients CEUS led to an improved delineation in comparison to BUS and showed a high-resolution imaging quality of the tumour margins and tumour boarders. Grade II and grade III astrocytoma (n = 6) as well as metastasis (n = 18) also showed high contrast agent uptake, which led in 50 % to an improved imaging quality. In 5 of these 17 patients, intraoperative CEUS for resection control showed tumour remnants, leading to further tumour resection. Patients treated with CEUS showed no increased neurological deficits after tumour resection. No pharmacological side-effects occurred. Three-dimensional CEUS is a reliable intraoperative imaging modality and could improve imaging quality. Ninety percent of the high-grade gliomas (HGG, glioblastoma and astrocytoma grade III) showed high contrast uptake with an improved imaging quality in more than 50 %. Gross total resection and incomplete resection of glioblastoma were adequately highlighted by 3D CEUS intraoperatively. The application of US contrast agent could be a helpful imaging tool, especially for resection control in glioblastoma surgery.

Objectives To examine differences in growth trajectories of fetal brain fissures in the growth restricted fetus (FGR) compared to controls. Methods We selected a subgroup of 227 women with a singleton pregnancy from the Rotterdam Periconceptional Cohort. Participants received three-dimensional ultrasound (3D-US) examinations of the fetal brain at 22, 26 and 32 weeks of gestational age (GA). The left and right Sylvian, insula and parieto-occipital fissures (POF) were measured in standardized planes. Linear mixed models with adjustment for potential confounders were applied to estimate differences between the trajectories of brain fissure depth measurements of FGR and controls. Results 22 FGR and 172 controls provided 31 and 504 3D-US respectively for longitudinal brain fissure depth measurements. Success rates for the Sylvian and insula depth measurements were over 80% and for POF over 62% at all GA. In FGR compared to controls, the trajectory of the right Sylvian fissure depth was significantly decreased (s = -4.30, 95%CI = -8.03;-0.56, p = 0.024) while its growth rate was slightly increased (s = 0.02, 95%CI = 0.00;0.04, p = 0.04), after adjustment for GA, head circumference, gender, educational level and parity. Conclusions The small differences in brain fissure measurements between 22 and 32 weeks GA in FGR warrant further investigation in larger cohorts with postnatal follow-up.

To examine the inter-rater reliability for the diagnosis of LSV on cranial ultrasound (cUS), determine the risk factors associated with LSV and its progression, and examine neurodevelopmental outcome. Prospective case–control study of neonates ≤32wks of gestation assessed for LSV by serial cUS (n = 1351) between 2012 and 2014 and their neurodevelopment at 18–36mon-corrected age compared to controls. Agreement for LSV on cUS improved from Κappa 0.4–0.7 after establishing definitive criteria and guidelines. BPD was the only variable associated with the occurrence and the progression of LSV. Cytomegalovirus (CMV) infection occurred in one neonate (1.5%). Neurodevelopmental outcome of neonates with LSV did not differ from controls. Establishment of well-defined stages of LSV improves the reliability of the diagnosis and allows identification of neonates with progression of LSV. Although LSV was associated with BPD, it was not associated with congenital CMV infection.

Objective Measurement of the optic nerve sheath diameter (ONSD) by using sonography is a straightforward, noninvasive technique to detect an increased intracranial pressure, which can even be conducted at the bedside. However, the correlation between ONSD and intracranial midline shift has not been studied. Methods The authors performed a prospective, blinded observational study in an intensive care unit. Forty-five patients were divided into groups. Of those, 19 patients had a midline shift, whereas 26 had no intracranial pathology or shift and served as control individuals. Results Spearman rank correlation coefficient of difference of ONSD and midline shift was 0.761 ( P Conclusions Despite small numbers and selection bias, this study suggests that bedside ultrasound may be useful in the diagnosis of midline intracranial shift by measurement of ONSD.

This article emphasizes technical factors that are helpful for optimizing sonographic examinations of the brain in preterm and term neonates. It also reviews existing data regarding the accuracy of neurosonographic examinations relative to MR. Many neurosonographic signs are subtle and can be easily overlooked, which could lead to delayed diagnosis or misdiagnosis. Therefore meticulous attention to sonographic technique is required to maximize the diagnostic utility of this modality. Although MR images of the brain often depict abnormalities more clearly than sonography, neurosonography continues to be an exceptionally valuable tool for evaluation of the neonatal brain, even in full-term neonates. Furthermore, its accuracy is greater, even in the latter age group, than many older publications suggest. Prospective studies using state-of-the-art equipment comparing findings on sonography and MR are needed to better understand how the accuracy of these modalities changes with refinements in equipment and to help us better understand the role of neurosonography relative to MR.

International audience; We developed an integrated experimental framework that extends the brain exploration capabilities of functional ultrasound imaging to awake and mobile rats. In addition to acquiring hemodynamic data, this method further allows parallel access to electroencephalography (EEG) recordings of neuronal activity. We illustrate this approach with two proofs of concept: a behavioral study on theta rhythm activation in a maze running task and a disease-related study on spontaneous epileptic seizures.

Innovative imaging methods help to investigate the complex relationship between brain activity and behavior in freely moving animals. Functional ultrasound (fUS) is an imaging modality suitable for recording cerebral blood volume (CBV) dynamics in the whole brain but has so far been used only in head-fixed and anesthetized rodents. We designed a fUS device for tethered brain imaging in freely moving rats based on a miniaturized ultrasound probe and a custom-made ultrasound scanner. We monitored CBV changes in rats during various behavioral states such as quiet rest, after whisker or visual stimulations, and in a food-reinforced operant task. We show that fUS imaging in freely moving rats could efficiently decode brain activity in real time.

Lenticulostriate vasculopathy (LSV) refers to increased echogenicity of the penetrating vessels that supply the basal ganglia and segments of the internal capsule seen on cranial ultrasound. Initially identified in infants with congenital infection, LSV has now been associated with a variety of infectious and non-infectious conditions. Although robust epidemiologic studies are lacking, the available evidence does not support broad evaluation for multiple congenital infections when LSV is identified. We propose screening infants with LSV for congenital cytomegalovirus infection and ensuring that prenatal screening included appropriate testing for syphilis, human immunodeficiency virus, and rubella-immune status. Large, prospective observational studies are needed to determine the incidence of LSV and the relative contribution of infectious and non-infectious conditions to LSV in the neonate.

There have been tremendous changes in the methods used to evaluate brain injury in the preterm infant in the past 30 years. In particular, major improvements have been made in how we use neuroimaging techniques and now magnetic resonance imaging (MRI) is used more often and considered complimentary to routine and sequential cranial ultrasound. The focus has shifted from severe lesions such as large intraventricular and parenchymal hemorrhages and cystic periventricular leukomalacia to assessing and understanding the etiology of more subtle noncystic white matter injury, punctate hemorrhage, and cerebellar lesions. The more severe lesions that dominated the early period of preterm neonatal brain imaging occur less frequently but are still associated with major disabilities, such as, cerebral palsy, while subtle white matter injury and cerebellar lesions are more often associated with cognitive and behavioral problems, which have become the most prevalent issues among the survivors of extremely preterm birth.

Combination of various intraoperative imaging modalities potentially can reduce error of brain shift estimation during neurosurgical operations. In the present work, a new combination of surface imaging and Doppler US images is proposed to calculate the displacements of cortical surface and deformation of internal vessels in order to estimate the targeted brain shift using a Finite Element Model (FEM). Registration error in each step and the overall performance of the method are evaluated. The preoperative steps include constructing a FEM from MR images and extracting vascular tree from MR Angiography (MRA). As the first intraoperative step, after the craniotomy and with the dura opened, a designed checkerboard pattern is projected on the cortex surface and projected landmarks are scanned and captured by a stereo camera (Int J Imaging Syst Technol 23(4):294–303, 2013. doi: 10.1002/ima.22064 ). This 3D point cloud should be registered to boundary nodes of FEM in the region of interest. For this purpose, we developed a new non-rigid registration method, called finite element drift that is more compatible with the underlying nature of deformed object. The presented algorithm outperforms other methods such as coherent point drift when the deformation is local or non-coherent. After registration, the acquired displacement vectors are used as boundary conditions for FE model. As the second step, by tracking a 2D Doppler ultrasound probe swept on the parenchyma, a 3D image of deformed vascular tree is constructed. Elastic registration of this vascular point cloud to the corresponding preoperative data results the second series of displacement vector applicable to closest internal nodes of FEM. After running FE analysis, the displacement of all nodes is calculated. The brain shift is then estimated as displacement of nodes in boundary of a deep target, e.g., a tumor. We used intraoperative MR (iMR) images as the references for measuring the performance of the brain shift estimator. In the present study, two set of tests were performed using: (a) a deformable brain phantom with surface data and (b) an alive brain of an approximately big dog with surface data and US Doppler images. In our designed phantom, small tubes connected to an inflatable balloon were considered as displaceable targets and in the animal model, the target was modeled by a cyst which was created by an injection. In the phantom study, the registration error for the surface points before FE analysis and for the target points after running FE model were $${

Screening neuroimaging helps in detecting clinically silent brain injury in extremely low birth weight (ELBW) preterm infants.1 Cranial ultrasound (CUS) is commonly used in ELBW newborns for routine screening; early CUS examination mostly detects hemorrhagic lesions, whereas a later CUS usually allows diagnosis of white matter abnormalities, including cystic periventricular leukomalacia (cPVL).2 Among all the white matter abnormalities, detection of cPVL on the late CUS examination has the highest correlation with neuropathologic findings3,4 and subsequent neurodevelopmental outcome.5–9 The late timing of the screening neuroimaging for detection of cPVL is intended to maximize cost-effectiveness, by focusing on time points when almost all cases of cPVL are expected to become evident on neuroimaging.10 The timing of “late” ultrasound examination varies with different guidelines for screening; the Canadian Pediatric Society recommends later CUS examination in the6thweekof life,2 and the American Academy of Neurology and the Child Neurology Society recommend it to be done between 36 and 40weeks’ postmenstrual age (PMA).1,11 However, studies in ELBW infants using serial CUS have shown that in some instances cPVL may be apparent for only 1 to 2 weeks before the cysts coalesce, collapse, and then disappear.12,13 If the later cranial screening imaging is deferred until 36 to 40 weeks’ PMA some cases of cPVL, especially in more premature ELBW infants, may be missed because the screening cranial imaging might be performed after the cysts collapsed and disappeared. For example, using the criterion of 36 to 40 weeks, PMA for an infant born at 23 weeks’ gestational age (GA), the later screening imaging would be performed at 13 to 17 weeks’ chronological age (CA). This same infant would be screened earlier, at 29 weeks’ PMA, using the Canadian Pediatric Society CA criterion of 6 weeks. This 7- to 11-week difference in obtaining routine cranial screening imaging may be crucial, if it results in underestimation of cPVL. We hypothesize that “late” screening cranial imaging only at 36 to 40 weeks PMA as recommended by the American Academy of Neurology and the Child Neurology Society will underestimate the incidence of cPVL in ELBW infants. We also hypothesize that cPVL underdetection at 36 to 40 weeks PMA will increase as GA at birth decreases because of longer delay in obtaining cranial screening imaging in infants who are more preterm. To explore this hypothesis, we assessed the detection of cPVL on screening cranial imaging performed closest to 36 weeks’ PMA (PMA criterion) compared with an earlier time point (CUS performed within 28 days CA) to determine if some cPVL had resolved by the time of later screening cranial imaging. We also compared the cPVL detection rate between ELBW infants born at < 26 weeks’ GA and those born at 26 to 28 weeks’ GA using PMA and CA criteria to determine if the incidence of potentially missed cases of cPVL differs between the two groups. This information might assist clinicians to provide better prognostic information to guide long-term care strategies in high-risk preterm neonates.

Severe intracranial hemorrhages occur especially in very immature premature infants born with a gestational age under 28 weeks of gestation and a birth weight below 1000 g. Severe hemorrhages are often complicated by a post-hemorrhagic hydrocephalus (PHH). PHH can be caused by a blockage of the cerebro-spinal fluid pathways or by obliterative arachnoiditis of the posterior cranial fossa. Cerebral sonography can differentiate between both entities. In cases of obstruction of the cerebro-spinal fluid circulation the parts of the ventricular system infront of the obstruction are dilated. Color coded Doppler sonography can display the patency or obstruction of the physiologic constrictions of the ventricular system. Increased intracranial pressure can noninvasively be detected by spectral Doppler: The increase of the peak systolic flow velocity in the intracranial section of the internal carotid artery in comparison with the extra-cranial part is an early indication of a raised intracranial pressure. The decrease of the end-diastolic flow velocity during fontanel compression is indicative of abolished cranial compliance and increased intracranial pressure. In the case of raised intracranial pressure diastolic amplitudes and end-diastolic flow velocities are decreased and the resistive-indices are increased.

Objective To study the incidence, clinical presentation, risk factors, imaging diagnosis, and clinical outcome of perinatal stroke. Methods Data was retrospectively collected from full-term newborns admitted to the neonatal unit of a level III maternity in Lisbon with cerebral stroke, from January 2007 to December 2011. Results There were 11 cases of stroke: nine were arterial ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke. Eight patients presented with symptoms while the remaining three were asymptomatic and incidentally diagnosed. The most frequently registered symptoms (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8). Strokes were more commonly left-sided (9/11), and the most affected artery was the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive in most of the patients (10/11), and stroke was confirmed by cerebral magnetic resonance in all patients. Electroencephalographic recordings were carried out in five patients and were abnormal in three (focal abnormalities n=2, burst-suppression pattern n=1). Eight patients had previously identified risk factors for neonatal stroke which included obstetric and neonatal causes. Ten patients were followed up at outpatients setting; four patients developed motor deficits and one presented with epilepsy. Conclusions Although a modest and heterogeneous sample, this study emphasizes the need for a high level of suspicion when it comes to neonatal stroke, primarily in the presence of risk factors. The prevalence of neurological sequelae in our series supports the need of long-term follow-up and early intervention strategies. Objetivo Estudar incidência, apresentação clínica, fatores de risco, resultado de exames de imagem e desfecho clínico do acidente vascular cerebral perinatal. Métodos Análise retrospectiva dos prontuários de recém-nascidos a termo internados com o diagnóstico de acidente vascular cerebral perinatal no Serviço de Neonatologia, de uma maternidade nível III, em Lisboa, de janeiro de 2007 a dezembro de 2011. Resultados Houve 11 casos de acidente vascular cerebral: nove isquêmicos arteriais e duas tromboses dos seios venosos. As incidências foram estimadas: para acidente vascular cerebral isquêmico arterial de 1,6/5.000 nascimentos; para trombose dos seios venosos de 7,2/100.000 nascimentos. Houve dois casos de recorrência. Oito doentes foram sintomáticos e três assintomáticos, com diagnóstico incidental. As convulsões foram o sintoma mais frequente (8/11): clônicas generalizadas (3/8) e clônicas focais (5/8). O território vascular esquerdo foi o mais afetado (9/11), particularmente a artéria cerebral média esquerda (8/11). A ecografia transfontanelar foi positiva na maioria dos doentes (10/11), sendo o diagnóstico confirmado por ressonância magnética cerebral em todos. Dos cinco doentes que realizam eletroencefalograma, três apresentaram alterações (alterações focais n=2 e padrão de surto-supressão n=1). Oito doentes apresentaram fatores de risco para acidente vascular cerebral neonatal, incluindo causas obstétricas e neonatais. Dez doentes foram acompanhados em ambulatório, dos quais quatro apresentaram défice motores e um apresentou epilepsia. Conclusão Apesar de uma amostra limitada e heterogênea, este estudo reforça a necessidade de um elevado nível de suspeita para acidente vascular cerebral perinatal, particularmente na presença de fatores de risco. A prevalência de sequelas neurológicas em nossa série reforça a necessidade de seguimento a longo prazo e de estratégias de intervenção precoces.

OBJECTIVE: To investigate detection ability and feasibility of serial cranial ultrasonography (CUS) and early MRI in preterm brain injury. DESIGN: Prospective cohort study. SETTING: Level III neonatal intensive care unit. PATIENTS: 307 infants, born below 29 weeks of gestation. METHODS: Serial CUS and MRI were performed according to standard clinical protocol. In case of instability, MRI was postponed or cancelled. Brain images were assessed by independent experts and compared between modalities. MAIN OUTCOME MEASURES: Presence of preterm brain injury on either CUS or MRI and discrepant imaging findings on CUS and MRI. RESULTS: Serial CUS was performed in all infants; early MRI was often postponed (n=59) or cancelled (n=126). Injury was found in 146 infants (47.6%). Clinical characteristics differed significantly between groups that were subdivided according to timing of MRI. 61 discrepant imaging findings were found. MRI was superior in identifying cerebellar haemorrhage; CUS in detection of acute intraventricular haemorrhage, perforator stroke and cerebral sinovenous thrombosis. CONCLUSIONS: Advanced serial CUS seems highly effective in diagnosing preterm brain injury, but may miss cerebellar abnormalities. Although MRI does identify these lesions, feasibility is limited. Improved safety, better availability and tailored procedures are essential for MRI to increase its value in clinical care.

To audit the management of ST-segment elevation myocardial infarction (STEMI) patients admitted to a New Zealand Hospital over three 14-day periods to review their number, characteristics, management and outcome changes over a decade.The acute coronary syndrome (ACS) audits were conducted over 14 days in May of 2002, 2007 and 2012 at New Zealand Hospitals admitting patients with a suspected or definite ACS. Longitudinal analyses of the STEMI subgroup are reported.From 2002 to 2012, the largest change in management was the proportion of patients undergoing reperfusion by primary PCI from 3% to 15% and 41%; P0.001, and the rates of second antiplatelet agent use in addition to aspirin from 14% to 62% and 98%; P0.001. The use of proven secondary prevention medications at discharge also increased during the decade. There were also significant increases in cardiac investigations for patients, especially echocardiograms (35%, 62% and 70%, P0.001) and invasive coronary angiograms (31%, 58% and 87%, P0.001). Notably even in 2012, one in four patients presenting with STEMI did not receive any reperfusion therapy.Substantial improvements have been seen in the management of STEMI patients in New Zealand over the last decade, in accordance with evidenced-based guideline recommendations. However, there appears to be considerable room to optimise management, particularly with the use of timely reperfusion therapy for more patients.

BackgroundFamilial restrictive cardiomyopathy (FRCM) has a poor prognosis due to diastolic dysfunction and restrictive physiology (RP). Myocardial stiffness, with or without fibrosis, underlie RP, but the mechanism(s) of restrictive remodeling is unclear. Myopalladin (MYPN) is a messenger molecule that links structural and gene regulatory molecules via translocation from the Z-disk and I-bands to the nucleus in cardiomyocytes. Expression of N-terminal MYPN peptide results in severe disruption of the sarcomere.ObjectivesThe aim was to study a nonsense MYPN-Q529X mutation previously identified in the FRCM family in an animal model to explore the molecular and pathogenic mechanisms of FRCM.MethodsFunctional (echocardiography, cardiac magnetic resonance [CMR] imaging, electrocardiography), morphohistological, gene expression, and molecular studies were performed in knock-in heterozygote (MypnWT/Q526X) and homozygote mice harboring the human MYPN-Q529X mutation.ResultsEchocardiographic and CMR imaging signs of diastolic dysfunction with preserved systolic function were identified in 12-week-old MypnWT/Q526X mice. Histology revealed interstitial and perivascular fibrosis without overt hypertrophic remodeling. Truncated MypnQ526X protein was found to translocate to the nucleus. Levels of total and nuclear cardiac ankyrin repeat protein (Carp/Ankrd1) and phosphorylation of mitogen-activated protein kinase/extracellular signal–regulated kinase 1/2 (Erk1/2), Erk1/2, Smad2, and Akt were reduced. Up-regulation was evident for muscle LIM protein (Mlp), desmin, and heart failure (natriuretic peptide A [Nppa], Nppb, and myosin heavy chain 6) and fibrosis (transforming growth factor beta 1, alpha–smooth muscle actin, osteopontin, and periostin) markers.ConclusionsHeterozygote MypnWT/Q526X knock-in mice develop RCM due to persistence of mutant MypnQ526X protein in the nucleus. Down-regulation of Carp and up-regulation of Mlp and desmin appear to augment fibrotic restrictive remodeling, and reduced Erk1/2 levels blunt a hypertrophic response in MypnWT/Q526X hearts.

Paediatric and particularly neonatal neurosonography still remains a mainstay of imaging the neonatal brain. It can be performed at the bedside without any need for sedation or specific monitoring. There are a number of neurologic conditions that significantly influence morbidity and mortality in neonates and infants related to the brain and the spinal cord; most of them can be addressed by ultrasonography (US). However, with the introduction of first CT and then MRI, neonatal neurosonography is increasingly considered just a basic first line technique that offers only orienting information and does not deliver much relevant information. This is partially caused by inferior US performance - either by restricted availability of modern equipment or by lack of specialized expertise in performing and reading neurosonographic scans. This essay tries to highlight the value and potential of US in the neonatal brain and briefly touching also on the spinal cord imaging. The common pathologies and their US appearance as well as typical indication and applications of neurosonography are listed. The review aims at encouraging paediatric radiologists to reorient there imaging algorithms and skills towards the potential of modern neurosonography, particularly in the view of efficacy, considering growing economic pressure, and the low invasiveness as well as the good availability of US that can easily be repeated any time at the bedside.

Background Intraventricular hemorrhage is rare in term newborns. Severe asphyxia is recognized as one of the risk factors of intraventricular hemorrhage in these newborns. Therapeutic hypothermia, which is the only available treatment for the limitation of brain injury in term asphyxiated newborns, may cause fluctuations of cerebral blood flow, possibly placing the newborn more at risk for intraventricular hemorrhage. The literature regarding the incidence of intraventricular hemorrhage in the context of neonatal hypoxic-ischemic encephalopathy and hypothermia is sparse. Methods We present a clinical observation and review the literature regarding the risk factors for intraventricular hemorrhage in term asphyxiated newborns treated with hypothermia. Results We describe the clinical course of a term newborn with severe hypoxic-ischemic encephalopathy who developed significant intraventricular hemorrhage during the rewarming period after the 72-hour hypothermia. Conclusion This newborn presented several risk factors for intraventricular hemorrhage, including severe asphyxia, hemodynamic instability, hemostasis disturbances, instrument delivery, venous sinus thrombosis, and hypoglycemia. Hypothermia and rewarming also may have contributed by causing fluctuations in cerebral blood flow.

To evaluate electroencephalogram (EEG) patterns in very low birth weight premature newborns when reaching term-to-term neonates, thereby comparing extra uterine to intra uterine development.EEG recordings were obtained between 2 and 14 days of life in 47 preterm (37 weeks) very low birth weight (⩽1500 g) newborns and repeated when reaching term age (38-42 weeks) in a subsample (n=22). EEG recordings were also obtained in term newborns. Clinical evaluation was performed at birth and at 6 and 12 months.Relative to the first EEG, preterm newborns showed a reduction in delta brushes and interburst intervals and increased interhemispheric synchrony, suggesting an improvement in EEG maturation. Further organization in sleep patterns, like a reduction in total sleep time and phase shifts, were also observed. However, when reaching term, preterm newborns still had less mature EEG patterns, phase shifts and transitional sleep than matched controls. Background abnormalities and dysmaturity in preterm newborns during the first EEG predicted adverse neurological outcome later on.EEG patterns in preterm very low birth weight newborns might be influenced by extra uterine development. Specific EEG abnormalities are related to increased risk of neurological disorders.Extra uterine development of very low birth weight delays the acquisition of maturational EEG patterns.

Transcranial B-mode sonography (TCS) of brain parenchyma is being increasingly used as a diagnostic tool in movement disorders. Compared to other neuroimaging modalities such as magnetic resonance imaging (MRI) and computed tomography, TCS can be performed today with portable machines and has the advantages of noninvasiveness and high resistance to movement artifacts. In distinct brain disorders TCS detects abnormalities that cannot be visualized or can only be visualized with significant effort with other imaging methods. In the field of movement disorders, TCS has been established mainly as a tool for the early and differential diagnosis of Parkinson's disease. The postoperative position control of deep brain stimulation electrodes, especially in the subthalamic nucleus, can reliably and safely be performed with TCS. The present update review summarizes the current methodological standards and defines quality criteria of adequate TCS imaging and assessment of diagnostically relevant deep brain structures such as substantia nigra, brainstem raphe, basal ganglia and ventricles. Finally, an overview is given on recent technological advances including TCS-MRI fusion imaging and upcoming technologies of digitized image analysis aiming at a more investigator-independent assessment of deep brain structures on TCS.

Despite improvements in neonatal care, survivors of preterm birth are still at a significantly increased risk of developing life-long neurological difficulties including cerebral palsy and cognitive difficulties. Cranial ultrasound is routinely used in neonatal practice, but has a low sensitivity for identifying later neurodevelopmental difficulties. Magnetic Resonance Imaging (MRI) can be used to identify intracranial abnormalities with greater diagnostic accuracy in preterm infants, and theoretically might improve the planning and targeting of long-term neurodevelopmental care; reducing parental stress and unplanned healthcare utilisation; and ultimately may improve healthcare cost effectiveness. Furthermore, MR imaging offers the advantage of allowing the quantitative assessment of the integrity, growth and function of intracranial structures, thereby providing the means to develop sensitive biomarkers which may be predictive of later neurological impairment. However further work is needed to define the accuracy and value of diagnosis by MR and the techniques's precise role in care pathways for preterm infants.

Brain-shift is a major source of error in neuronavigation systems based on pre-operative images. In this paper, we present intra-operative correction of brain-shift using 3D ultrasound. The method is based on image registration of vessels extracted from pre-operative MRA and intra-operative power Doppler-based ultrasound and is fully integrated in the neuronavigation software. We have performed correction of brain-shift in the operating room during surgery and provided the surgeon with updated information. Here, we present data from seven clinical cases with qualitative and quantitative error measures. The registration algorithm is fast enough to provide the surgeon with updated information within minutes and accounts for large portions of the experienced shift. Correction of brain-shift can make pre-operative data like fMRI and DTI reliable for a longer period of time and increase the usefulness of the MR data as a supplement to intra-operative 3D ultrasound in terms of overview and interpretation.

Focused ultrasound (FUS) in the presence of microbubbles can bring about transcranial and local opening of the blood-brain barrier (BBB) for potential noninvasive delivery of drugs to the brain. A phased-array ultrasound system is essential for FUS-BBB opening to enable electronic steering and correction of the focal beam which is distorted by cranial bone. Here, we demonstrate our prototype design of a 256-channel ultrasound phased-array system for large-region transcranial BBB opening in the brains of large animals. One of the unique features of this system is the capability of generating concurrent dual-frequency ultrasound signals from the driving system for potential enhancement of BBB opening. A wide range of signal frequencies can be generated (frequency = 0.2-1.2 MHz) with controllable driving burst patterns. Precise output power can be controlled for individual channels via 8-bit duty-cycle control of transistor-transistor logic signals and the 8-bit microcontroller-controlled buck converter power supply output voltage. The prototype system was found to be in compliance with the electromagnetic compatibility standard. Moreover, large animal experiments confirmed the phase switching effectiveness of this system, and induction of either a precise spot or large region of BBB opening through fast focal-beam switching. We also demonstrated the capability of dual-frequency exposure to potentially enhance the BBB-opening effect. This study contributes to the design of ultrasound phased arrays for future clinical applications, and provides a new direction toward optimizing FUS brain drug delivery.

Objective The objective of this article is to describe the diagnostic significance of prenatal identification of dilated supra-pineal recess (SPR) in cases of ventriculomegaly. Method A retrospective study, based on neurosonography and magnetic resonance imaging, of a series of five prenatal cases referred to our institution because of ventriculomegaly associated with dilatation of the SPR. Results Ventriculomegaly of obstructive origin was diagnosed in all cases and related to obstruction downstream of the third ventricle. The diagnosis in the five prenatal cases, confirmed on early post-natal imaging, included the following: malformative aqueductal stenosis, ischemic–haemorrhagic parenchymal supra-tentorial insult complicated by aqueductal stenosis, Blake's pouch cyst, cystic lesion of the posterior fossa and sub-ependymal haemorrhage and Dandy–Walker malformation. In all cases, the third ventricle was prominent and associated with a dilated SPR. In two cases, the dilatation of the SPR was an early clue to e obstructive ventriculomegaly, which was initially minor and became severe on follow-up imaging. Conclusion The presence of a dilated SPR prenatally in the presence of even mild ventriculomegaly should prompt evaluation and follow-up for the presence of obstructive ventriculomegaly with obstruction located downstream of the third ventricle. © 2014 John Wiley & Sons, Ltd.

Aim The aim of the study was to compare clinical and neuroimaging characteristics and neurodevelopmental outcome in preterm infants with a periventricular haemorrhagic infarction (PVHI) located in the temporal or frontal periventricular white matter. Method The study was a retrospective hospital-based study of preterm infants with a frontal PVHI (n=21; 11 males, 10 females; mean birthweight 1527g; mean gestational age 30.3wks) or temporal PVHI (n=13; five males, eight females; mean birthweight 1205g; mean gestational age 30.2wks) admitted to the neonatal intensive care unit between 1990 and 2012. The clinical course, results of neuroimaging studies, and neurodevelopmental outcomes of preterm infants with a gestational age less than 34 weeks with a confirmed PVHI on early cranial ultrasonography and/or magnetic resonance imaging were reviewed. For assessment of neurodevelopmental outcome we used the Griffiths Mental Development Scales, the Movement Assessment Battery for Children, the Gross Motor Function Classification System, the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and ophthalmological assessment. An unfavourable neurodevelopmental outcome was defined as moderately or severely atypical neurological examination during the last visit: presence of cerebral palsy, epilepsy, a hearing or visual impairment, and/or atypical cognitive development (Griffiths Mental Development Scales developmental quotient or Wechsler Preschool and Primary Scale of Intelligence

Object Cerebrospinal fluid shunt ventricular catheters inserted into the frontal horn or trigone are associated with prolonged shunt survival. Developing surgical techniques for accurate catheter insertion could, therefore, be beneficial to patients. This study was conducted to determine if the rate of accurate catheter location with intraoperative ultrasound guidance could exceed 80%. Methods The authors conducted a prospective, multicenter study of children (< 18 years) requiring first-time treatment for hydrocephalus with a ventriculoperitoneal shunt. Using intraoperative ultrasound, surgeons were required to target the frontal horn or trigone for catheter tip placement. An intraoperative ultrasound image was obtained at the time of catheter insertion. Ventricular catheter location, the primary outcome measure, was determined from the first postoperative image. A control group of patients treated by nonultrasound surgeons (conventional surgeons) were enrolled using the same study criteria. Conventional shunt surgeons also agreed to target the frontal horn or trigone for all catheter insertions. Patients were triaged to participating surgeons based on call schedules at each center. A pediatric neuroradiologist blinded to method of insertion, center, and surgeon determined ventricular catheter tip location. Results Eleven surgeons enrolled as ultrasound surgeons and 6 as conventional surgeons. Between February 2009 and February 2010, 121 patients were enrolled at 4 Hydrocephalus Clinical Research Network centers. Experienced ultrasound surgeons (> 15 cases prior to study) operated on 67 patients; conventional surgeons operated on 52 patients. Experienced ultrasound surgeons achieved accurate catheter location in 39 (59%) of 66 patients, 95% CI (46%–71%). Intraoperative ultrasound images were compared with postoperative scans. In 32.7% of cases, the catheter tip moved from an accurate location on the intraoperative ultrasound image to an inaccurate location on the postoperative study. This was the most significant factor affecting accuracy. In comparison, conventional surgeons achieved accurate location in 24 (49.0%) of 49 cases (95% CI [34%–64%]). The shunt survival rate at 1 year was 70.8% in the experienced ultrasound group and 66.9% in the conventional group (p = 0.66). Ultrasound surgeons had more catheters surrounded by CSF (30.8% vs 6.1%, p = 0.0012) and away from the choroid plexus (72.3% vs 58.3%, p = 0.12), and fewer catheters in the brain (3% vs 22.4%, p = 0.0011) and crossing the midline (4.5% vs 34.7%, p < 0.001), but they had a higher proportion of postoperative pseudomeningocele (10.1% vs 3.8%, p = 0.30), wound dehiscence (5.8% vs 0%, p = 0.13), CSF leak (10.1% vs 1.9%, p = 0.14), and shunt infection (11.6% vs 5.8%, p = 0.35). Conclusions Ultrasound-guided shunt insertion as performed in this study was unable to consistently place catheters into the frontal horn or trigone. The technique is safe and achieves outcomes similar to other conventional shunt insertion techniques. Further efforts to improve accurate catheter location should focus on prevention of catheter migration that occurs between intraoperative placement and postoperative imaging. Clinical trial registration no.: NCT01007786 (ClinicalTrials.gov).

Acute pulmonary embolism (APE) is the third most common cause of death in the United States. Appearing as a sudden blockage in a major pulmonary artery, APE may cause mild, moderate or severe right ventricular (RV) overload. Although severe RV overload produces diagnostically obvious RV mechanical failure, little progress has been made in gaining a clinical and biophysical understanding of moderate and mild acute RV overload and its impact on RV functionality. In the research described here, we conducted a pilot study in pigs using echocardiography and observed the following abnormalities in RV functionality under acute mild or moderate RV overload: (i) occurrence of paradoxical septal motion with "waving" dynamics; (ii) decrease in local curvature of the septum (p 0.01); (iii) lower positive correlation between movement of the RV free wall and movement of the septum (p 0.05); (iv) slower rate of RV fractional area change (p 0.05); and (v) decrease in movement stability, particularly in the middle of the septum (p 0.05).

The study was designed to determine the effects of two protocols of sedation, medetomidine and medetomidine-butorphanol, on cerebral blood flow (CBF) by transcranial color-coded Duplex ultrasonography in healthy dogs. Transcranial Doppler ultrasonographic examination was performed in 20 dogs before and 20 min after sedation with either medetomidine (group 1) or medetomidine-butorphanol (group 2). The left and right middle cerebral arteries (LMCA and RMCA) were evaluated using the temporal windows, and the basilar artery (BA) was studied through the suboccipital window. Peak systolic velocity (PSV), mean velocity (MV), end diastolic velocity (EDV), resistance index (RI), and pulsatility index (PI) were measured for each vessel. Blood pressure (BP) and heart rate (HR) were also recorded before and after sedation in both groups. Statistically significant differences were found for PSV, MV and EDV when RMCA and LMCA were interrogated before and after sedation. PSV, RI and PI were found to be statistically significantly different when the study was performed on the BA. These results should be taken in account when a transcranial Doppler is performed in dogs sedated with the mentioned protocols and it might suggest some degree of neuroprotection.