Development of neonatal-specific sequences for portable ultralow field magnetic resonance brain imaging: a prospective, single-centre, cohort study.

Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3-53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas' and South London & Maudsley NHS Foundation Trusts and King's College London.

Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear. PURPOSE: To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes. STUDY TYPE: Retrospective case-control study. POPULATION: Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery. FIELD STRENGTH/SEQUENCE: T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner. ASSESSMENT: Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups. STATISTICAL TESTS: ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR -values <0.05 were considered statistically significant. RESULTS: Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios. DATA CONCLUSION: Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Individual Assessment of Perioperative Brain Growth Trajectories in Infants With Congenital Heart Disease: Correlation With Clinical and Surgical Risk Factors.

Background Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. Methods and Results A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. Z-scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of Z-score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate P<0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate P=0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate P=0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate P<0.027). Conclusions Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short- and long-term hypoxic injury.

Brain white-matter changes associated with symptomatic acute COVID-19 infection in the neonatal period.

We report an important case of periventricular white matter damage in a 1-month-old infant, demonstrated on high quality structural (T2) and diffusion weighted magnetic resonance imaging. The infant was born at term following an uneventful pregnancy and discharged home shortly after, but was brought to the paediatric emergency department five days after birth with seizures and respiratory distress, testing positive for COVID-19 infection on PCR. These images highlight the need to consider brain MRI in all infants with symptomatic SARS-Cov-2 infection, and show how this infection can lead to extensive white matter damage in the context of multisystem inflammation.

In vivo T1 mapping of neonatal brain tissue at 64 mT.

PURPOSE: Ultralow-field (ULF) point-of-care MRI systems allow image acquisition without interrupting medical provision, with neonatal clinical care being an important potential application. The ability to measure neonatal brain tissue T1 is a key enabling technology for subsequent structural image contrast optimization, as well as being a potential biomarker for brain development. Here we describe an optimized strategy for neonatal T1 mapping at ULF. METHODS: Examinations were performed on a 64-mT portable MRI system. A phantom validation experiment was performed, and a total of 33 in vivo exams were acquired from 28 neonates with postmenstrual age ranging from 31+4 to 49+0  weeks. Multiple inversion-recovery turbo spin-echo sequences were acquired with differing inversion and repetition times. An analysis pipeline incorporating inter-sequence motion correction generated proton density and T1 maps. Regions of interest were placed in the cerebral deep gray matter, frontal white matter, and cerebellum. Weighted linear regression was used to predict T1 as a function of postmenstrual age. RESULTS: Reduction of T1 with postmenstrual age is observed in all measured brain tissue; the change in T1 per week and 95% confidence intervals is given by dT1  = -21 ms/week [-25, -16] (cerebellum), dT1  = -14 ms/week [-18, -10] (deep gray matter), and dT1  = -35 ms/week [-45, -25] (white matter). CONCLUSION: Neonatal T1 values at ULF are shorter than those previously described at standard clinical field strengths, but longer than those of adults at ULF. T1 reduces with postmenstrual age and is therefore a candidate biomarker for perinatal brain development.

High resolution and contrast 7 tesla MR brain imaging of the neonate.

Introduction: Ultra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system. Methods: Images were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM). Results: There was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy. Discussion: We demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.

Fifteen-minute consultation: Investigation and management of hypoglycaemia in the term-born infant.

Hypoglycaemia in term infants is very common. Deciding on appropriate investigations and management is often challenging. The aims of this article are to help with understanding when, how and why to investigate symptoms of hypoglycaemia in full-term infants (born ≥37 weeks' gestational age).

Delivery room cuddles for extremely preterm babies and parents: concept, practice, safety, parental feedback.

AIM: Following extreme preterm birth, there has traditionally been felt an imperative to rush baby to the neonatal unit for ongoing intensive care. Immediate needs of parents to bond with their babies through direct early physical contact have often been overlooked; many weeks can pass before parents get to hold their babies for the first time. Recognition of the importance of early contact is growing. We aimed to review the safety and value of routinely practising delivery room cuddles for extremely preterm babies. METHODS: We reviewed delivery room cuddles in babies born <27 weeks' gestation in our centre between 2006 and 2017 via case-control. We also conducted a questionnaire survey of mothers who experienced a delivery room cuddle to gain their feedback and perspectives. RESULTS: We found no difference in age or temperatures on neonatal unit admission. There was no case of inadvertent extubation associated with cuddles. Parental feedback was very positive. CONCLUSION: With appropriate safeguards, delivery room cuddles are feasible and achievable for extremely preterm babies irrespective of birth gestation. Facilitation of the cuddle is an early and very important family-centred care practice which seems much appreciated by parents and which may improve bonding, lactation, and maternal mental health.

Parental perceptions of the impact of neonatal unit visitation policies during COVID-19 pandemic.

OBJECTIVES: To ascertain parental perceptions of the impact of restricted visiting policies to neonatal intensive care units during the current COVID-19 pandemic. DESIGN: Cross-sectional survey of parents impacted by visitation policies. SETTING: Six tertiary level neonatal units, four from the UK and two from the USA, participated in the study. PARTICIPANTS: Parents and families of infants hospitalised in the participating centres between 1 May 2020 and 21 August 2020. METHODS: Online-based and/or paper-based survey, querying the visitation policies and their impact on parents' ability to visit, care for and bond with their infants. RESULTS: A total of 231 responses were received. Visitation limited to a single visitor with no restrictions on duration was the most frequently reported policy; 140/217 (63%). Visitation policies were perceived as being restrictive by 62% (138/219) of the respondents with 37% (80/216) reporting being able to visit less often than desired, 41% (78/191) reporting being unable to bond enough and 27% (51/191) reporting not being able to participate in their baby's daily care. Mild to severe impact on breast feeding was reported by 36% (75/209) of respondents. Stricter policies had a higher impact on families and were significantly associated with a lack of bonding time, inability to participate in care and an adverse impact on breast feeding. CONCLUSIONS: Visitation policies during the COVID-19 pandemic varied between centres and over time with stricter restrictions implemented earlier on in the pandemic. Parents reported significant impacts on their ability to visit, care for and bond with their infants with perceived severity of impact worse with stricter restrictions.

Fifteen-minute consultation: Therapeutic hypothermia for infants with hypoxic ischaemic encephalopathy-translating jargon, prognosis and uncertainty for parents.

Hypoxic ischaemic encephalopathy may lead to death or severe long-term morbidity. Therapeutic hypothermia (TH) increases survival without impairments in childhood, but prognostic uncertainty may remain for years after birth. Clear and accurate communication is imperative but challenging. This article explores the predictive value of routinely performed assessments during TH, as well as the qualitative research relating to parental experience. This article will benefit paediatric trainees, consultants and nurse practitioners in providing: (1) the background information needed for initiating a conversation with parents regarding outcome and (2) optimising their communication with parents in translating jargon, prognosis and uncertainty.

Does Magnetic Resonance Brain Scanning at 3.0 Tesla Pose a Hyperthermic Challenge to Term Neonates?

Next-generation 3-Tesla magnetic resonance (MR) scanners offer improved neonatal neuroimaging, but the greater associated radiofrequency radiation may increase the risk of hyperthermia. Safety data for neonatal 3-T MR scanning are lacking. We measured rectal temperatures continuously in 25 neonates undergoing 3-T brain MR imaging and observed no significant hyperthermic threat.