Scalable Transdiagnostic Early Assessment of Mental Health (STREAM): a study protocol.

INTRODUCTION: Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant 'detection gap' where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions. METHODS AND ANALYSIS: The STREAM project will enrol and assess 4000 children aged 0-6 years from Malawi (n=2000) and India (n=2000). It integrates three established developmental assessment tools measuring motor, social and cognitive functioning using gamified tasks, observation checklists, parent-report and audio-video recordings. Domain scores for motor, social and cognitive functioning will be developed and assessed for their validity and reliability. These domain scores will then be used to construct age-adjusted developmental reference curves. ETHICS AND DISSEMINATION: Ethical approval has been obtained from local review boards at each site (India: Sangath Institutional Review Board; All India Institute of Medical Science (AIIMS) Ethics Committee; Indian Council of Medical Research-Health Ministry Screening Committee; Malawi: College of Medicine Research and Ethics Committee; Malawi Ministry of Health-Blantyre District Health Office). The study adheres to Good Clinical Practice standards and the ethical guidelines of the 6th (2008) Declaration of Helsinki. Findings from STREAM will be disseminated to participating families, healthcare professionals, policymakers, educators and researchers, at local, national and international levels through meetings, academic journals and conferences.

Attention control in autism: Eye-tracking findings from pre-school children in a low- and middle-income country setting.

LAY ABSTRACT: The development of cognitive processes, such as attention control and learning, has been suggested to be altered in children with a diagnosis of autism spectrum disorder. However, nearly all of our understanding of the development of these cognitive processes comes from studies with school-aged or older children in high-income countries, and from research conducted in a controlled laboratory environment, thereby restricting the potential generalisability of results and away from the majority of the world's population. We need to expand our research to investigate abilities beyond these limited settings. We address shortcomings in the literature by (1) studying attention control and learning in an understudied population of children in a low- and middle-income country setting in India, (2) focusing research on a critical younger age group of children and (3) using portable eye-tracking technology that can be taken into communities and healthcare settings to increase the accessibility of research in hard-to-reach populations. Our results provide novel evidence on differences in attention control and learning responses in groups of children with and without a diagnosis of autism spectrum disorder. We show that learning responses in children that we assessed through a portable eye-tracking task, called the 'antisaccade task', may be specific to autism. This suggests that the methods we use may have the potential to identify and assess autism-specific traits across development, and be used in research in low-resource settings.

Using mobile health technology to assess childhood autism in low-resource community settings in India: An innovation to address the detection gap.

LAY ABSTRACT: Autism is diagnosed by highly trained professionals- but most autistic people live in parts of the world that harbour few or no such autism specialists and little autism awareness. So many autistic people go undiagnosed, misdiagnosed, and misunderstood. We designed an app (START) to identify autism and related conditions in such places, in an attempt to address this global gap in access to specialists. START uses computerised games and activities for children and a questionnaire for parents to measure social, sensory, and motor skills. To check whether START can flag undiagnosed children likely to have neurodevelopmental conditions, we tested START with children whose diagnoses already were known: Non-specialist health workers with just a high-school education took START to family homes in poor neighbourhoods of Delhi, India to work with 131 two-to-seven-year-olds. Differences between typically and atypically developing children were highlighted in all three types of skills that START assesses: children with neurodevelopmental conditions preferred looking at geometric patterns rather than social scenes, were fascinated by predictable, repetitive sensory stimuli, and had more trouble with precise hand movements. Parents' responses to surveys further distinguished autistic from non-autistic children. An artificial-intelligence technique combining all these measures demonstrated that START can fairly accurately flag atypically developing children. Health workers and families endorsed START as attractive to most children, understandable to health workers, and adaptable within sometimes chaotic home and family environments. This study provides a proof of principle for START in digital screening of autism and related conditions in community settings.

Mapping the link between socio-economic factors, autistic traits and mental health across different settings.

LAY ABSTRACT: Autistic individuals are more likely than non-autistic individuals to experience a mental health condition in their lifetime, and this includes externalising and internalising symptoms. We know very little about how different environments and family conditions impact these symptoms for autistic individuals. Improving our understanding of these relationships is important so that we can identify individuals who may be in greater need of support. In this article, we seek to improve our understanding of how environmental and family conditions impact externalising and internalising symptoms in autistic and non-autistic people. To do this, we conducted analyses with two cohorts in very different settings - in Europe and South Africa - to ensure our findings are globally representative. We used advanced statistical methods to establish environmental and family conditions that were similar to each other, and which could be combined into specific 'factors'. We found that four similar 'factors' could be identified in the two cohorts. These were distinguished by personal characteristics and environmental conditions of individuals, and were named Person Characteristics, Family System, Parental and Material Resources. Interestingly, just 'Family System' was associated with internalising and externalising symptoms, and this was the same in both cohorts. We also found that having high traits of autism impacted this relationship between Family System and mental health conditions with opposite directions in the two settings. These results show that characteristics in the Family System are associated with internalising and externalising symptoms, and autistic persons are particularly impacted, reinforcing the notion that family stressors are important to consider when implementing policy and practice related to improving the mental health of autistic people.

Caregiver Perceptions of Autism and Neurodevelopmental Disabilities in New Delhi, India.

Evidence suggests that parenting an autistic child or a child with neurodevelopmental disabilities can be more challenging than parenting a child meeting their developmental milestones, especially when there is a dearth of support services, such as in low- and middle-income countries (LMICs). Despite the majority of the world's children residing in LMICs, there are limited studies examining the understanding of developmental disorders and autism in these regions. We therefore aim to investigate perceptions of autism and developmental disabilities in caregivers of children in an urban setting in New Delhi, India. Thirteen semi-structured interviews with parents/caregivers of children were conducted in three groups: (1) caregivers with a child with a diagnosis of autism spectrum disorder (ASD); (2) caregivers with a child with a diagnosis of intellectual disability (ID); (3) and caregivers with children meeting their developmental milestones. Transcripts were analysed using framework analysis. Three themes on the impact of cultural and contextual factors on the recognition, interpretation, and reporting of autistic symptoms are discussed, and additional themes focus on the impact of diagnosis and family support. Our findings highlighted a vital need for greater community awareness and recognition of autism in India, for example through community and healthcare training, which may help to reduce stigma and facilitate wider family support.

Cognitive Enhancement and Social Mobility: Skepticism from India.

Cognitive enhancement (CE) covers a broad spectrum of methods, including behavioral techniques, nootropic drugs, and neuromodulation interventions. However, research on their use in children has almost exclusively been carried out in high-income countries with limited understanding of how experts working with children view their use in low- and middle- income countries (LMICs). This study examines perceptions on cognitive enhancement, their techniques, neuroethical issues about their use from an LMICs perspective.Seven Indian experts were purposively sampled for their expertise in bioethics, child development and child education. In-depth interviews were conducted using a semi-structured topic guide to examine (1) understanding of CE, (2) which approaches were viewed as cognitive enhancers, (3) attitudes toward different CE techniques and (4) neuroethical issues related to CE use within the Indian context. All interviews were audio recorded and transcribed before thematic analysis.Findings indicate Indian experts view cognitive enhancement as a holistic positive impact on overall functioning and well-being, rather than improvement in specific cognitive abilities. Exogenous agents, and neuromodulation were viewed with skepticism, whereas behavioral approaches were viewed more favorably. Neuroethical concerns included equitable access to CE, limited scientific evidence and over-reliance on technology to address societal problems. This highlights the need for more contextually relevant neuroethics research in LMICs.

Homelessness in autistic women: Defining the research agenda.

BACKGROUND: Current evidence suggests that autistic individuals are at high risk for becoming and remaining in a cycle of homelessness. Key risk factors for homelessness disproportionately affect autistic people; however, we have limited understanding of how to best support autistic individuals accessing services. This gap in the evidence base is particularly acute for autistic women. OBJECTIVE: As a first step to address this gap, we aimed to (1) map gaps in knowledge and practice; (2) identify priority areas for research and (3) develop recommendations for how to implement novel research and practice in this area. METHODS: We conducted a collaborative workshop with an interdisciplinary group of 26 stakeholders to address our aims. Stakeholders included autistic women with experience of homelessness, researchers, health professionals, NGO representatives, and service providers. RESULTS AND RECOMMENDATIONS: Two research priority areas were identified to map the prevalence and demographics of autistic women experiencing homelessness, and to delineate risk and protective factors for homelessness. Priority areas for improving provision of support included staff training to improve communication, awareness of autism and building trust with service providers, and recommendations for practical provision of support by services. CONCLUSIONS: Future research is critical to increase our knowledge of the pathways leading to homelessness for autistic women, and barriers to engaging with homelessness and social services. We need to use this knowledge to develop new ways of delivering targeted and inclusive support for autistic women, which could prevent or shorten periods of homelessness.

Digital tools for direct assessment of autism risk during early childhood: A systematic review.

LAY ABSTRACT: The challenge of finding autistic children, and finding them early enough to make a difference for them and their families, becomes all the greater in parts of the world where human and material resources are in short supply. Poverty of resources delays interventions, translating into a poverty of outcomes. Digital tools carry potential to lessen this delay because they can be administered by non-specialists in children's homes, schools or other everyday environments, they can measure a wide range of autistic behaviours objectively and they can automate analysis without requiring an expert in computers or statistics. This literature review aimed to identify and describe digital tools for screening children who may be at risk for autism. These tools are predominantly at the 'proof-of-concept' stage. Both portable (laptops, mobile phones, smart toys) and fixed (desktop computers, virtual-reality platforms) technologies are used to present computerised games, or to record children's behaviours or speech. Computerised analysis of children's interactions with these technologies differentiates children with and without autism, with promising results. Tasks assessing social responses and hand and body movements are the most reliable in distinguishing autistic from typically developing children. Such digital tools hold immense potential for early identification of autism spectrum disorder risk at a large scale. Next steps should be to further validate these tools and to evaluate their applicability in a variety of settings. Crucially, stakeholders from underserved communities globally must be involved in this research, lest it fail to capture the issues that these stakeholders are facing.

From the lab to the field: acceptability of using electroencephalography with Indian preschool children.

Background: Measurement of social and cognitive brain development using electroencephalography (EEG) offers the potential for early identification of children with elevated risk of developmental delay. However, there have been no published reports of how acceptable EEG technology is to parents and children within communities, especially in low-resource contexts such as in low and middle income countries (LMICs), which is an important question for the potential scalability of these assessments. We use a mixed-methods approach to examine whether EEG assessments are acceptable to children and their caregivers in a low resource community setting in India. Methods: We assessed the acceptability of neurophysiology research and Braintools (a novel neurodevelopmental assessment toolkit using concurrent EEG and eye-tracking technology) using: 1) a child engagement measure, 2) interviews with caregivers (n=8); 3) survey about caregiver's experience (n=36). Framework analysis was used to analyse interview data. Results: A high level of child engagement in EEG tasks was demonstrated, with children's gaze at the screen during the task averaging at 85.4% (±12.06%) of the task time. External distractions and noise during the tasks were measured, but not found to significantly effect child's attention to the screen during EEG tasks. Key topics were examined using the framework analysis: 1) parental experience of the assessment; and 2) the acceptability of research. From topic 1, four sub-themes were identified: i) caregivers' experience of the assessment, ii) caregivers' perception of child's experience of assessment, iii) logistical barriers and facilitators to participation, and iv) recommendations for improvement. Results from interviews and the survey indicated acceptability for gaze-controlled EEG research for parents and children. From topic 2, three themes were identified: i) caregivers' understanding of the research, ii) barriers to participation, and iii) facilitators to participation. Barriers to participation mainly included logistical challenges, such as geographic location and time, whereas involvement of the wider family in decision making was highlighted as an important facilitator to partake in the research. Conclusions: We demonstrate for the first time the acceptability of conducting neurodevelopmental assessments using concurrent EEG and eye-tracking in preschool children in uncontrolled community LMIC settings. This kind of research appears to be acceptable to the community and we identify potential barriers and facilitators of this research, thus allowing for future large scale research projects to be conducted investigating neurodevelopment and risk factors for suboptimal development in LMICs.

"I was Confused and Still am" Barriers Impacting the Help-Seeking Pathway for an Autism Diagnosis in Urban North India: A Mixed Methods Study.

Timely recognition of autism in children is integral to improve developmental outcomes. This study used mixed-methods (84 case-registers and 20 in-depth interviews with caregivers of children with a diagnosis of autism) to explore the extent to which the nature of parental concerns and prior knowledge of developmental disorders impact the time between symptom recognition and autism diagnosis, and the contextual family, societal and health-system related factors that impede the autism help-seeking pathway. Lack of awareness of age-appropriate child developmental milestones, apparent amongst the community and health professionals, contributed to a 1.5-year delay between parental concerns and autism diagnosis. Recommendations to shorten this help-seeking pathway include harnessing the potential of non-specialist workers to increase awareness and enable developmental monitoring of young children through scalable tools.

Barriers to Autism Spectrum Disorder Diagnosis for Young Women and Girls: a Systematic Review.

There is increased recognition that women and girls with autism spectrum disorders (ASD) are underserved by the clinical criteria and processes required to receive a diagnosis. This mixed-methods systematic review aimed to identify key barriers to obtaining an ASD diagnosis in girls and young women under 21 years. Six themes were identified that focused on perceived gendered symptoms, namely behavioural problems, social and communication abilities, language, relationships, additional diagnoses/difficulties and restricted and repetitive behaviours and interests. Five themes were identified as (parental) perceived barriers to diagnosis, namely compensatory behaviours, parental concerns, others' perceptions, lack of information/resources and clinician bias. This review highlights the importance of enhancing widespread understanding and recognition of ASD presentation in females across development. PROSPERO Centre for Reviews and Dissemination (ID 2018 CRD42018087235). SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s40489-020-00225-8) contains supplementary material, which is available to authorized users.

The association between maternal lifetime interpersonal trauma experience and perceived mother-infant bonding.

BACKGROUND: Interpersonal traumas are common among expectant and new mothers and are found to have considerable impacts on women's mental health. These experiences may disrupt maternal perceptions of the mother-infant relationship, which is essential for healthy infant development, but findings are inconsistent. This study aims to explore associations between lifetime interpersonal traumas and their impact on self-reported mother-infant bonding. METHODS: Secondary data analysis of a representative cohort of 453 women attending at a South London maternity service. Lifetime interpersonal trauma experience and its association with self-reported mother-infant bonding (Postpartum Bonding Questionnaire) was assessed in uni- and multivariable linear regressions, the latter adjusted to account for antenatal depressive and posttraumatic symptoms, measured using the Edinburgh Postnatal Depression Scale and Posttraumatic Stress Disorder Scale, and key sociodemographic risk factors. RESULTS: Maternal lifetime trauma was not associated with perceived difficulties in mother-infant bonding at three months postnatal; however antenatal depressive symptoms, both with continuous EPDS score (0.33, 95% CI 0.17-0.50, p<0.001) and clinical cut-off ≥13 (4.26, 95% CI 2.02-6.49, p<0.001) were associated with self-reported bonding difficulties. LIMITATIONS: The composite trauma measurement did not allow for a comprehensive assessment of individual trauma types. CONCLUSIONS: There was no evidence for a link between maternal lifetime trauma experiences and self-reported bonding difficulties. However, an association between antenatal depressive symptoms and perceived postpartum bonding impairment was found. This highlights the importance of identification and treatment of depressive symptoms during pregnancy and offering women support in facilitating a positive mother-infant relationship.

Emerging ethical issues raised by highly portable MRI research in remote and resource-limited international settings.

Smaller, more affordable, and more portable MRI brain scanners offer exciting opportunities to address unmet research needs and long-standing health inequities in remote and resource-limited international settings. Field-based neuroimaging research in low- and middle-income countries (LMICs) can improve local capacity to conduct both structural and functional neuroscience studies, expand knowledge of brain injury and neuropsychiatric and neurodevelopmental disorders, and ultimately improve the timeliness and quality of clinical diagnosis and treatment around the globe. Facilitating MRI research in remote settings can also diversify reference databases in neuroscience, improve understanding of brain development and degeneration across the lifespan in diverse populations, and help to create reliable measurements of infant and child development. These deeper understandings can lead to new strategies for collaborating with communities to mitigate and hopefully overcome challenges that negatively impact brain development and quality of life. Despite the potential importance of research using highly portable MRI in remote and resource-limited settings, there is little analysis of the attendant ethical, legal, and social issues (ELSI). To begin addressing this gap, this paper presents findings from the first phase of an envisioned multi-staged and iterative approach for creating ethical and legal guidance in a complex global landscape. Section 1 provides a brief introduction to the emerging technology for field-based MRI research. Section 2 presents our methodology for generating plausible use cases for MRI research in remote and resource-limited settings and identifying associated ELSI issues. Section 3 analyzes core ELSI issues in designing and conducting field-based MRI research in remote, resource-limited settings and offers recommendations. We argue that a guiding principle for field-based MRI research in these contexts should be including local communities and research participants throughout the research process in order to create sustained local value. Section 4 presents a recommended path for the next phase of work that could further adapt these use cases, address ethical and legal issues, and co-develop guidance in partnership with local communities.

EEG signatures of cognitive and social development of preschool children-a systematic review.

BACKGROUND: Early identification of preschool children who are at risk of faltering in their development is essential to ensuring that all children attain their full potential. Electroencephalography (EEG) has been used to measure neural correlates of cognitive and social development in children for decades. Effective portable and low-cost EEG devices increase the potential of its use to assess neurodevelopment in children at scale and particularly in low-resource settings. We conducted a systematic review aimed to synthesise EEG measures of cognitive and social development in 2-5-year old children. Our secondary aim was to identify how these measures differ across a) the course of development within this age range, b) gender and c) socioeconomic status (SES). METHODS AND FINDINGS: A systematic literature search identified 51 studies for inclusion in this review. Data relevant to the primary and secondary aims was extracted from these studies and an assessment for risk of bias was done, which highlighted the need for harmonisation of EEG data collection and analysis methods across research groups and more detailed reporting of participant characteristics. Studies reported on the domains of executive function (n = 22 papers), selective auditory attention (n = 9), learning and memory (n = 5), processing of faces (n = 7) and emotional stimuli (n = 8). For papers investigating executive function and selective auditory attention, the most commonly reported measures were alpha power and the amplitude and latency of positive (P1, P2, P3) and negative (N1, N2) deflections of event related potential (ERPs) components. The N170 and P1 ERP components were the most commonly reported neural responses to face and emotional faces stimuli. A mid-latency negative component and positive slow wave were used to index learning and memory, and late positive potential in response to emotional non-face stimuli. While almost half the studies described changes in EEG measures across age, only eight studies disaggregated results based on gender, and six included children from low income households to assess the impact of SES on neurodevelopment. No studies were conducted in low- and middle-income countries. CONCLUSION: This review has identified power across the EEG spectrum and ERP components to be the measures most commonly reported in studies in which preschool children engage in tasks indexing cognitive and social development. It has also highlighted the need for additional research into their changes across age and based on gender and SES.

Higher Order Spherical Harmonics Reconstruction of Fetal Diffusion MRI With Intensity Correction.

We present a novel method for higher order reconstruction of fetal diffusion MRI signal that enables detection of fiber crossings. We combine data-driven motion and intensity correction with super-resolution reconstruction and spherical harmonic parametrisation to reconstruct data scattered in both spatial and angular domains into consistent fetal dMRI signal suitable for further diffusion analysis. We show that intensity correction is essential for good performance of the method and identify anatomically plausible fiber crossings. The proposed methodology has potential to facilitate detailed investigation of developing brain connectivity and microstructure in-utero.

Young pregnant women and risk for mental disorders: findings from an early pregnancy cohort.

BACKGROUND: Young women aged 16-24 are at high risk of common mental disorders (CMDs), but the risk during pregnancy is unclear.AimsTo compare the population prevalence of CMDs in pregnant women aged 16-24 with pregnant women ≥25 years in a representative cohort, hypothesising that younger women are at higher risk of CMDs (depression, anxiety disorders, post-traumatic stress disorder, obsessive-compulsive disorder), and that this is associated with low social support, higher rates of lifetime abuse and unemployment. METHOD: Analysis of cross-sectional baseline data from a cohort of 545 women (of whom 57 were aged 16-24 years), attending a South London maternity service, with recruitment stratified by endorsement of questions on low mood, interviewed with the Structured Clinical Interview DSM-IV-TR. RESULTS: Population prevalence estimates of CMDs were 45.1% (95% CI 23.5-68.7) in young women and 15.5% (95% CI 12.0-19.8) in women ≥25, and for 'any mental disorder' 67.2% (95% CI 41.7-85.4) and 21.2% (95% CI 17.0-26.1), respectively. Young women had greater odds of having a CMD (adjusted odds ratio (aOR) = 5.8, 95% CI 1.8-18.6) and CMDs were associated with living alone (aOR = 3.0, 95% CI 1.1-8.0) and abuse (aOR = 1.5, 95% CI 0.8-2.8). CONCLUSIONS: Pregnant women between 16 and 24 years are at very high risk of mental disorders; services need to target resources for pregnant women under 25, including those in their early 20s. Interventions enhancing social networks, addressing abuse and providing adequate mental health treatment may minimise adverse outcomes for young women and their children.Declaration of interestNone.

White and grey matter development in utero assessed using motion-corrected diffusion tensor imaging and its comparison to ex utero measures.

OBJECTIVE: Fetal brain diffusion tensor imaging (DTI) offers quantitative analysis of the developing brain. The objective was to 1) quantify DTI measures across gestation in a cohort of fetuses without brain abnormalities using full retrospective correction for fetal head motion 2) compare results obtained in utero to those in preterm infants. MATERIALS AND METHODS: Motion-corrected DTI analysis was performed on data sets obtained at 1.5T from 32 fetuses scanned between 21.29 and 37.57 (median 31.86) weeks. Results were compared to 32 preterm infants scanned at 3T between 27.43 and 37.14 (median 33.07) weeks. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were quantified by region of interest measurements and tractography was performed. RESULTS: Fetal DTI was successful in 84% of fetuses for whom there was sufficient data for DTI estimation, and at least one tract could be obtained in 25 cases. Fetal FA values increased and ADC values decreased with age at scan (PLIC FA: p = 0.001; R2 = 0.469; slope = 0.011; splenium FA: p < 0.001; R2 = 0.597; slope = 0.019; thalamus ADC: p = 0.001; R2 = 0.420; slope = - 0.023); similar trends were found in preterm infants. CONCLUSION: This study demonstrates that stable DTI is feasible on fetuses and provides evidence for normative values of diffusion properties that are consistent with aged matched preterm infants.

Thailand's national universal developmental screening programme for young children: action research for improved follow-up.

INTRODUCTION: In low-income and middle-income countries, it is estimated that one in every three preschool-age children are failing to meet cognitive or socioemotional developmental milestones. Thailand has implemented a universal national developmental screening programme (DSPM) for young children to enable detection of developmental disorders and early intervention that can improve child health outcomes. DSPM implementation is being hampered by low attendance at follow-up appointments when children fail the initial screening. METHODS: Action research, using qualitative methods was conducted with 19 caregivers, 5 health workers and 1 chief at two Health Promotion Hospitals to explore the factors affecting attendance at follow-up appointments. Transcripts and notes were analysed using descriptive content analysis. Findings were then discussed with 48 health workers, managers, researchers and policymakers. RESULTS: The high workload of health workers during busy vaccination clinics, and inadequate materials prevented clear communication with caregivers about the screening, how to stimulate child development and the screening result. Caregivers, particularly grandparents, had a lack of understanding about how to stimulate child development, and did not fully understand failed screening results. Caregivers felt blamed for not stimulating their child's development, and were either worried that their child was severely disabled, or they did not believe the screening result and therefore questioned its usefulness. This led to a lack of attendance at follow-up appointments. CONCLUSION: Task-sharing, mobile health (mhealth), community outreach and targeted interventions for grandparent caregivers might increase awareness about child development and screening, and allow health workers more time to communicate effectively. Sharing best practices, communication training and mentoring of DSPM workers coupled with mhealth job aids could also improve caregiver attendance at follow-up. Engagement of caregivers in understanding the barriers to attendance at follow-up and engagement of stakeholders in the design and implementation of interventions is important to ensure their effectiveness.

Distortion Correction in Fetal EPI Using Non-Rigid Registration With a Laplacian Constraint.

Geometric distortion induced by the main B0 field disrupts the consistency of fetal echo planar imaging (EPI) data, on which diffusion and functional magnetic resonance imaging is based. In this paper, we present a novel data-driven method for simultaneous motion and distortion correction of fetal EPI. A motion-corrected and reconstructed T2 weighted single shot fast spin echo (ssFSE) volume is used as a model of undistorted fetal brain anatomy. Our algorithm interleaves two registration steps: estimation of fetal motion parameters by aligning EPI slices to the model; and deformable registration of EPI slices to slices simulated from the undistorted model to estimate the distortion field. The deformable registration is regularized by a physically inspired Laplacian constraint, to model distortion induced by a source-free background B0 field. Our experiments show that distortion correction significantly improves consistency of reconstructed EPI volumes with ssFSE volumes. In addition, the estimated distortion fields are consistent with fields calculated from acquired field maps, and the Laplacian constraint is essential for estimation of plausible distortion fields. The EPI volumes reconstructed from different scans of the same subject were more consistent when the proposed method was used in comparison with EPI volumes reconstructed from data distortion corrected using a separately acquired B0 field map.

Correlating 3T MRI and histopathology in patients undergoing epilepsy surgery.

PURPOSE: To investigate whether specific semi-quantitative 3T MRI parameters are associated with particular histological features in temporal lobe specimens in epilepsy surgery patients whose conventional MRI scan appeared normal. These MRI techniques have the potential to visualise subtle structural abnormalities currently undetected on conventional MRI; but correlation between pre-operative in vivo MRI and histopathology is needed to understand the basis of these MRI abnormalities. Predicting subtle histopathology with semi-quantitative MRI techniques could contribute to pre-surgical evaluation of epilepsy patients. MATERIALS AND METHODS: MRI techniques: normalised FLAIR signal intensity (nFSI), grey matter probability and diffusion tensor imaging (DTI) were correlated with quantitative histopathological measures: NeuN (neuronal nuclear antigen); GFAP (glial fibrillary acidic protein) and MBP (myelin basic protein) field fractions and stereological neuronal densities obtained in grey and white matter regions in twenty-four patients who underwent anterior temporal lobe resections. RESULTS: There were no significant correlations between the histopathological measurements and MRI values in grey or white matter in macroscopically normal appearing tissue. CONCLUSION: Findings suggest that in macroscopically normal appearing tissue, the studied semiquantitative MRI measurements are not significantly related to the measures of gliosis, neuronal loss/gain and myelin used in the current study. Studies of macroscopically abnormal tissue as well as improvements to the MRI techniques may increase the sensitivity of future correlative studies to improve our understanding of the histopathological basis of MRI signal characteristics.