Pia Wintermark

Brain Perfusion in Asphyxiated Newborns Treated with Therapeutic Hypothermia

BACKGROUND AND PURPOSE: Induced hypothermia is thought to work partly by mitigating reperfusion injury in asphyxiated term neonates. The purpose of this study was to assess brain perfusion in the first week of life in these neonates. MATERIALS AND METHODS: In this prospective cohort study, MR imaging and ASL-PI were used to assess brain perfusion in these neonates. We measured regional CBF values on 1–2 MR images obtained during the first week of life and compared these with values obtained in control term neonates. The same or later MR imaging scans were obtained to define the extent of brain injury. RESULTS: Eighteen asphyxiated and 4 control term neonates were enrolled; 11 asphyxiated neonates were treated with hypothermia. Those developing brain injury despite being treated with induced hypothermia usually displayed hypoperfusion on DOL 1 and then hyperperfusion on DOL 2–3 in brain areas subsequently exhibiting injury. Asphyxiated neonates not treated with hypothermia who developed brain injury also displayed hyperperfusion on DOL 1–6 in brain areas displaying injury. CONCLUSIONS: Our data show that ASL-PI may be useful for identifying asphyxiated neonates at risk of developing brain injury, whether or not hypothermia is administered. Because hypothermia for 72 hours may not prevent brain injury when hyperperfusion is found early in the course of neonatal hypoxic-ischemic encephalopathy, such neonates may be candidates for adjustments in their hypothermia therapy or for adjunctive neuroprotective therapies.

Auditory brain development in premature infants: the importance of early experience

Preterm infants in the neonatal intensive care unit (NICU) often close their eyes in response to bright lights, but they cannot close their ears in response to loud sounds. The sudden transition from the womb to the overly noisy world of the NICU increases the vulnerability of these high‐risk newborns. There is a growing concern that the excess noise typically experienced by NICU infants disrupts their growth and development, putting them at risk for hearing, language, and cognitive disabilities. Preterm neonates are especially sensitive to noise because their auditory system is at a critical period of neurodevelopment, and they are no longer shielded by maternal tissue. This paper discusses the developmental milestones of the auditory system and suggests ways to enhance the quality control and type of sounds delivered to NICU infants. We argue that positive auditory experience is essential for early brain maturation and may be a contributing factor for healthy neurodevelopment. Further research is needed to optimize the hospital environment for preterm newborns and to increase their potential to develop into healthy children.

Placental pathology in asphyxiated newborns meeting the criteria for therapeutic hypothermia

OBJECTIVEnWe sought to describe placental findings in asphyxiated term newborns meeting therapeutic hypothermia criteria and to assess whether histopathologic correlation exists between these placental lesions and the severity of later brain injury.nnnSTUDY DESIGNnWe conducted a prospective cohort study of the placentas of asphyxiated newborns, in whom later brain injury was defined by magnetic resonance imaging.nnnRESULTSnA total of 23 newborns were enrolled. Eighty-seven percent of their placentas had an abnormality on the fetal side of the placenta, including umbilical cord lesions (39%), chorioamnionitis (35%) with fetal vasculitis (22%), chorionic plate meconium (30%), and fetal thrombotic vasculopathy (26%). A total of 48% displayed placental growth restriction. Chorioamnionitis with fetal vasculitis and chorionic plate meconium were significantly associated with brain injury (P = .03). Placental growth restriction appears to significantly offer protection against the development of these injuries (P = .03).nnnCONCLUSIONnTherapeutic hypothermia may not be effective in asphyxiated newborns whose placentas show evidence of chorioamnionitis with fetal vasculitis and chorionic plate meconium.

Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic–ischemic encephalopathy treated with hypothermia

BACKGROUNDnThe measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside.nnnOBJECTIVEnThe purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia.nnnDESIGN/METHODSnIn this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram.nnnRESULTSnTwelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE.nnnCONCLUSIONSnNIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE.

Early versus late MRI in asphyxiated newborns treated with hypothermia

Objective The purposes of this feasibility study were to assess: (1) the potential utility of early brain MRI in asphyxiated newborns treated with hypothermia; (2) whether early MRI predicts later brain injury observed in these newborns after hypothermia has been completed; and (3) whether early MRI indicators of brain injury in these newborns represent reversible changes. Patients and methods All consecutive asphyxiated term newborns meeting the criteria for therapeutic hypothermia were enrolled prospectively. Each newborn underwent one or two early MRI scans while receiving hypothermia, on day of life (DOL) 1 and DOL 2–3 and also one or two late MRI scans on DOL 8–13 and at 1 month of age. Results 37 MRI scans were obtained in 12 asphyxiated neonates treated with induced hypothermia. Four newborns developed MRI evidence of brain injury, already visible on early MRI scans. The remaining eight newborns did not develop significant MRI evidence of brain injury on any of the MRI scans. In addition, two patients displayed unexpected findings on early MRIs, leading to early termination of hypothermia treatment. Conclusions MRI scans obtained on DOL 2–3 during hypothermia seem to predict later brain injuries in asphyxiated newborns. Brain injuries identified during this early time appear to represent irreversible changes. Early MRI scans might also be useful to demonstrate unexpected findings not related to hypoxic–ischaemic encephalopathy, which could potentially be exacerbated by induced hypothermia. Additional studies with larger numbers of patients will be useful to confirm these results.

A DTI-based tractography study of effects on brain structure associated with prenatal alcohol exposure in newborns

Prenatal alcohol exposure (PAE) is known to have severe, long‐term consequences for brain and behavioral development already detectable in infancy and childhood. Resulting features of fetal alcohol spectrum disorders include cognitive and behavioral effects, as well as facial anomalies and growth deficits. Diffusion tensor imaging (DTI) and tractography were used to analyze white matter (WM) development in 11 newborns (age since conception <45 weeks) whose mothers were recruited during pregnancy. Comparisons were made with nine age‐matched controls born to abstainers or light drinkers from the same Cape Coloured (mixed ancestry) community near Cape Town, South Africa. DTI parameters, T1 relaxation time, proton density and volumes were used to quantify and investigate group differences in WM in the newborn brains. Probabilistic tractography was used to estimate and to delineate similar tract locations among the subjects for transcallosal pathways, cortico‐spinal projection fibers, and cortico‐cortical association fibers. In each of these WM networks, the axial diffusivity was the parameter that showed the strongest association with maternal drinking. The strongest relations were observed in medial and inferior WM, regions in which the myelination process typically begins. In contrast to studies of older individuals with PAE, fractional anisotropy did not exhibit a consistent and significant relation with alcohol exposure. To our knowledge, this is the first DTI‐tractography study of prenatally alcohol exposed newborns. Hum Brain Mapp, 36:170–186, 2015.

Perfusion Imaging of Focal Cortical Dysplasia Using Arterial Spin Labeling Correlation With Histopathological Vascular Density

Focal cortical dysplasia is the most common malformation of cortical development, causing intractable epilepsy. This study investigated the relationship between brain perfusion and microvessel density in 7 children with focal cortical dysplasia. The authors analyzed brain perfusion measurements obtained by magnetic resonance imaging of 2 of the children and the microvessel density of brain tissue specimens obtained by epilepsy surgery on all of the children. Brain perfusion was approximately 2 times higher in the area of focal cortical dysplasia compared to the contralateral side. The microvessel density was nearly double in the area of focal cortical dysplasia compared to the surrounding cortex that did not have morphological abnormalities. These findings suggest that hyperperfusion can be related to increased microvessel density in focal cortical dysplasia rather than only to seizures. Further investigations are needed to determine the relationship between brain perfusion, microvessel density, and seizure activity.

Measurement of brain perfusion in newborns: Pulsed arterial spin labeling (PASL) versus pseudo-continuous arterial spin labeling (pCASL)

Background Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns. Objective To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns. Design/methods We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas. Results A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001). Conclusion This study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures.

New Insights in Perinatal Arterial Ischemic Stroke by Assessing Brain Perfusion

Perinatal arterial ischemic stroke (AIS) is an important cause of long-term morbidity in children. Thus, there is an urgent need to better understand the mechanisms of stroke in newborns in order to develop effective treatment and prevention strategies. The purpose of this study was to assess brain perfusion within the first month of life in newborns with AIS. In this study, magnetic resonance imaging (MRI) and perfusion imaging by arterial spin labeling (ASL) were used to assess brain perfusion in four term newborns with AIS. One patient had a stroke within the territory of the right middle cerebral artery (MCA); the other three patients had a stroke within the territory of the left MCA. None of them displayed any hemorrhagic component. All four patients demonstrated abnormal brain perfusion in the stroke area. Cerebral blood flow (CBF) within the stroke area was increased in patient # 1. In all other three patients, CBF was decreased within the stroke center and increased in the periphery of the stroke area. These results show the feasibility of the ASL sequence in newborns with AIS and support its addition to the current MRI protocol used in these newborns as it provides useful information on brain hemodynamics. Its value for identifying salvageable tissue in newborns needs to be further assessed, as well as its potential role in stroke follow-up and for tissue-specific treatment screening.

MRI obtained during versus after hypothermia in asphyxiated newborns

Objective To assess whether the brain MRI results obtained during hypothermia identify the later brain injury observed in asphyxiated newborns after therapy is completed. Patients and methods Asphyxiated newborns treated with hypothermia were prospectively enrolled in this study if they had at least one MRI performed during hypothermia treatment and then another MRI performed around day 10 of life. Results A total of 129 MRI scans were obtained from 43 asphyxiated newborns treated with hypothermia. Sixty per cent developed brain injury; all the brain injuries observed on the late scans were already present on day 2–3 of life during hypothermia, and the extent of injury was similar between the early and late scans. The brain MRI on day 2–3 of life had a sensitivity of 100% (95% CI 84% to 100%) and a specificity of 100% (95% CI 77% to 100%) to identify the presence and extent of later brain injury. Conclusions The brain MRIs performed during hypothermia already permit an accurate definition of the presence and extent of brain injury that later develop in asphyxiated newborns despite treatment. These results may have research and clinical implications for the care of these newborns.