Christopher Kelly

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity.

Impaired development of the cerebral cortex in infants with congenital heart disease is correlated to reduced cerebral oxygen delivery

Neurodevelopmental impairment is the most common comorbidity associated with complex congenital heart disease (CHD), while the underlying biological mechanism remains unclear. We hypothesised that impaired cerebral oxygen delivery in infants with CHD is a cause of impaired cortical development, and predicted that cardiac lesions most associated with reduced cerebral oxygen delivery would demonstrate the greatest impairment of cortical development. We compared 30 newborns with complex CHD prior to surgery and 30 age-matched healthy controls using brain MRI. The cortex was assessed using high resolution, motion-corrected T2-weighted images in natural sleep, analysed using an automated pipeline. Cerebral oxygen delivery was calculated using phase contrast angiography and pre-ductal pulse oximetry, while regional cerebral oxygen saturation was estimated using near-infrared spectroscopy. We found that impaired cortical grey matter volume and gyrification index in newborns with complex CHD was linearly related to reduced cerebral oxygen delivery, and that cardiac lesions associated with the lowest cerebral oxygen delivery were associated with the greatest impairment of cortical development. These findings suggest that strategies to improve cerebral oxygen delivery may help reduce brain dysmaturation in newborns with CHD, and may be most relevant for children with CHD whose cardiac defects remain unrepaired for prolonged periods after birth.

Different patterns of cortical maturation before and after 38 weeks gestational age demonstrated by diffusion MRI in vivo

&NA; Human cortical development during the third trimester is characterised by macro‐ and microstructural changes which are reflected in alterations in diffusion MRI (dMRI) measures, with significant decreases in cortical mean diffusivity (MD) and fractional anisotropy (FA). This has been interpreted as reflecting increased cellular density and dendritic arborisation. However, the fall in FA stops abruptly at 38 weeks post‐menstrual age (PMA), and then tends to plateau, while MD continues to fall, suggesting a more complex picture and raising the hypothesis that after this age development is dominated by continuing increase in neural and organelle density rather than alterations in the geometry of dendritic trees. To test this, we used neurite orientation dispersion and density imaging (NODDI), acquiring multi‐shell, high angular resolution dMRI and measures of cortical volume and mean curvature in 99 preterm infants scanned between 25 and 47 weeks PMA. We predicted that increased neurite and organelle density would be reflected in increases in neurite density index (NDI), while a relatively unchanging geometrical structure would be associated with constant orientation dispersion index (ODI). As dendritic arborisation is likely to be one of the drivers of gyrification, we also predicted that measures of cortical volume and curvature would correlate with ODI and show slower growth after 38 weeks. We observed a decrease of MD throughout the period, while cortical FA decreased from 25 to 38 weeks PMA and then increased. ODI increased up to 38 weeks and then plateaued, while NDI rose after 38 weeks. The evolution of ODI correlated with cortical volume and curvature. Regional analysis of cortical microstructure revealed a heterogenous pattern with increases in FA and NDI after 38 weeks confined to primary motor and sensory regions. These results support the interpretation that cortical development between 25 and 38 weeks PMA shows a predominant increase in dendritic arborisation and neurite growth, while between 38 and 47 weeks PMA it is dominated by increasing cellular and organelle density. Graphical abstract Figure. No caption available. HighlightsDTI and NODDI cortical measures between 25 and 47 weeks GAEarly cortical changes consistent with dendritic arborisation and neurite growthAfter 38 weeks cortical changes consistent with increasing cellular densityCortical curvature evolves in parallel with dendritic arborisation

Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease

This review integrates data on brain dysmaturation and acquired brain injury using fetal and neonatal magnetic resonance imaging (MRI), including the contribution of cardiovascular physiology to differences in brain development, and the relationship between brain abnormalities and subsequent neurological impairments in infants with congenital heart disease (CHD). The antenatal and neonatal period are critical for optimal brain development; the developing brain is particularly vulnerable to haemodynamic disturbances during this time. Altered cerebral perfusion and decreased cerebral oxygen delivery in the antenatal period can affect functional and structural brain development, while postnatal haemodynamic fluctuations may cause additional injury. In critical CHD, brain dysmaturation and acquired brain injury result from a combination of underlying cardiovascular pathology and surgery performed in the neonatal period. MRI findings in infants with CHD can be used to evaluate potential clinical risk factors for brain abnormalities, and aid prediction of functional outcomes at an early stage. In addition, information on timing of brain dysmaturation and acquired brain injury in CHD has the potential to be used when developing strategies to optimize neurodevelopment.

Abnormal microstructural development of the cerebral cortex in neonates with congenital heart disease is associated with impaired cerebral oxygen delivery

Background Abnormal macrostructural development of the cerebral cortex has been associated with hypoxia in infants with congenital heart disease (CHD). Animal studies have suggested that hypoxia results in cortical dysmaturation at the cellular level. New magnetic resonance imaging (MRI) techniques offer the potential to investigate the relationship between cerebral oxygen delivery and microstructural development of the cortex in newborn infants with CHD. Methods We measured macrostructural and microstructural properties of the cortex in 48 newborn infants with complex CHD and 48 age-matched healthy controls. Cortical volume and gyrification index were calculated from high resolution structural MRI. Neurite density and orientation dispersion indices were modelled using high angular resolution diffusion MRI. Cerebral oxygen delivery was estimated in infants with CHD using phase contrast MRI and pre-ductal pulse oximetry. We used tract-based spatial statistics to examine voxel-wise group differences in cortical microstructure. Results Microstructural development of the cortex was abnormal in 48 infants with CHD, with regions of increased fractional anisotropy (FA) and reduced orientation dispersion index (ODI) compared to 48 healthy controls, correcting for gestational age at birth and scan (FWE-corrected for multiple comparisons at P<0.05). Regions of reduced cortical ODI in infants with CHD were related to impaired cerebral oxygen delivery (R2=0.637, n=39). Cortical ODI was associated with gyrification index (R2=0.589, P<0.0001, n=48). Conclusions This study suggests that the primary component of cerebral cortex dysmaturation in CHD is impaired dendritic arborisation, which may underlie abnormal macrostructural findings reported in this population. The degree of impairment was related to cerebral oxygen delivery, supporting the hypothesis that maternal oxygen therapy may be beneficial in this population.

Recent advances in diffusion neuroimaging: applications in the developing preterm brain

Measures obtained from diffusion-weighted imaging provide objective indices of white matter development and injury in the developing preterm brain. To date, diffusion tensor imaging (DTI) has been used widely, highlighting differences in fractional anisotropy (FA) and mean diffusivity (MD) between preterm infants at term and healthy term controls; altered white matter development associated with a number of perinatal risk factors; and correlations between FA values in the white matter in the neonatal period and subsequent neurodevelopmental outcome. Recent developments, including neurite orientation dispersion and density imaging (NODDI) and fixel-based analysis (FBA), enable white matter microstructure to be assessed in detail. Constrained spherical deconvolution (CSD) enables multiple fibre populations in an imaging voxel to be resolved and allows delineation of fibres that traverse regions of fibre-crossings, such as the arcuate fasciculus and cerebellar–cortical pathways. This review summarises DTI findings in the preterm brain and discusses initial findings in this population using CSD, NODDI, and FBA.

Promoting innovation in healthcare

ABSTRACT Innovation can be defined as invention + adoption + diffusion. In healthcare, it may be a novel idea, product, service or care pathway that has clear benefits when compared to what is currently done. Successful innovations often possess two key qualities: they are both usable and desirable. How can proven innovations be quickly and effectively adopted as best practice and taken up across the whole healthcare system? How can the commercial success of our ideas be realised at home rather than abroad, as has too often been the case? This review explores important issues of funding, information governance, interoperability, medical device regulation, procurement, clinical prototyping and the systemic challenge of encouraging and scaling innovation.

Open access video resource for paediatric exam revision

ing debriefing remains unknown. In advanced life support (ALS) training, one major challenge in conducting post-simulation debriefing is the difficulty in allowing trainees to both objectively and comprehensively review their practice in order to identify the gap between actual performance and the target goal. What was tried? A free iOS application, ‘CodeTracer’ (https://itunes.apple.com/us/app/codetracer/ id887099682?mt=8), was developed to aid creative learning and teaching in ALS simulation education. We introduced a novel presentation scheme into this App to allow participants to ‘visualise’ their performance by sequencing the registered interventions on a timeline map. The App also computes the overall no flow fraction (NFF) in simulated cardiac arrests. Data on every simulation can be saved on the device for real-time review, and for further comparison between different scenarios. A simple pilot study was conducted to gain quantitative evaluation of whether this particular tool could help in the debriefing after ALS simulations. Sixty participants were randomly assigned into teams of six. Each team completed a scenario of ALS simulation following a mini-lecture on learning objectives and practice guidelines in adult cardiac arrest resuscitation. A structured debriefing was held immediately after every simulation. Teams were then randomly assigned to receive either oral debriefing alone or App-assisted debriefing after the simulation. What lessons were learned? The response to our App-assisted ALS education was promising. Ninety per cent of the participants in the App-assisted group rated the software ‘helpful’ and ‘valuable’. They considered that ‘being able to implement the App’ for debriefing allowed them to be more interested and focused, as the software enables them to have an intuitive visual summary of which and when interventions were performed during their practice. We found some potential benefits of the App in our pilot study. First, participants receiving adjunctive data by the App in the debriefing sessions gave more and richer feedback on how their performances could be improved in the future (the technical skills gaps). For example, wrong or omitted actions or medications during resuscitation, or proper actions performed at the wrong time, can all be easily and rapidly recognized on the timeline graph by the App. These errors are strongly associated with adverse clinical outcomes in cardiac arrest resuscitations, and are difficult to identify by either memory recall or even video review. Second, we observed that a higher level of team collaboration could be achieved when objective indicators were provided for review. In our pilot study, debriefing with quantitative parameters (NFF, time to initiation of cardiopulmonary resuscitation [CPR] and to first defibrillation) was associated with more practical feedback on team performance, with emphasis on team communication, leadership and interpersonal collaboration in order to reduce unnecessary interruptions in chest compressions and to ensure rapid response to several time-sensitive interventions. Finally, it would be interesting to investigate in the future whether this App could complement the traditional checklist-based assessment by providing an additional scoring system for ALS simulation tests.

G573(P) Improving ease and accuracy of centile calculations with a smartphone implementation of rcpch uk-who growth charts

Context Improvement work performed while working as a paediatric trainee ST2 on a tertiary neonatal intensive care unit, neurosurgical ward and academic research department. Target audience: health professionals who calculate growth centiles on a regular basis. Problem Calculating growth centiles and their trends are a crucial part of the general paediatric and neonatal assessment. However, due to the regular scarcity of paper charts and inconvenience of trying to find one on a busy ward, centiles are often overlooked. Even with a chart available for use, the manual plotting method gives broad estimates rather than exact numbers (i.e. 25–50th centile), which are not appropriate for research purposes. Assessment of problem and analysis of its causes Working on a paediatric neurosurgical ward, the neurosurgical consultants complained that growth centiles were not being filled in consistently by junior doctors during clerking. A poll of fellow trainees agreed that an electronic version, available at the point of care, would be very beneficial. Problems with paper growth charts include lack of chart availability, time pressure, plotting inaccuracies, and inherent centile approximation due to threshold banding. Additionally, the calculation of corrected age for children and post menstrual ages for premature babies is commonly performed inaccurately. A solution to this problem would need to combine improved accuracy with greater ease of calculation, providing a tool that staff could carry with them everywhere at work. Intervention Creation of a smartphone app to calculate growth centiles for premature babies through to 18 year old children, using RCPCH UK-WHO data. The app also addresses the difficulty of calculating corrected ages by building this into the calculation. Strategy for change The provisional app was circulated to a number of interested paediatricians, and very helpful feedback received from the NHS Hackday group. The app was also discussed with Prof Tim Cole (the creator of the original growth charts), who provided some very helpful feedback and suggestions for improvement. The app was launched as a free download in October 2014 on iPhone and Android as a proof of concept via social media, and a significant amount of constructive feedback was received. An updated version is currently in progress, building in many of these suggestions. Measurement of improvement The project is at an early stage, and no objective metrics of improvement have yet been collected. It is hoped that this will be possible after the launch of the final version. Effects of changes The app is now being used in the research department at St Thomas’ to calculate accurate centiles for research participants at the Centre for the Developing Brain. Despite the deliberately local launch of the first version, the app has already been downloaded by 2,500 users. It is hoped that as the app gains adoption, the calculation of growth centiles in paediatric practice will become more widespread, with associated benefits to child health (Figure 1). Abstract G573(P) Figure 1 Lessons learnt I have learned about implementing a new tool in clinical practice, combined with gathering feedback and suggestions from a wide range of people to make the product as clinically useful as possible. Message for others Creating a web/app-based tool for commonly-performed error-prone tasks appears to be an effective strategy to improve quality at the bedside. There are many resources available online to guide interested people through this process.