Craniofacial phenotyping with fetal MRI: a feasibility study of 3D visualisation, segmentation, surface-rendered and physical models.

This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented.Qualitative analysis of multiplanar volumes, based on the SVR output and surface segmentations outputs, were assessed with computer and printed models, using standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24-36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66-100% visibility of relevant craniofacial and head structures in the SVR output, and 20-100% and 60-90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36%, demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20-36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing.Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy.Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment.

Real-time fetal brain tracking for functional fetal MRI.

PURPOSE: To improve motion robustness of functional fetal MRI scans by developing an intrinsic real-time motion correction method. MRI provides an ideal tool to characterize fetal brain development and growth. It is, however, a relatively slow imaging technique and therefore extremely susceptible to subject motion, particularly in functional MRI experiments acquiring multiple Echo-Planar-Imaging-based repetitions, for example, diffusion MRI or blood-oxygen-level-dependency MRI. METHODS: A 3D UNet was trained on 125 fetal datasets to track the fetal brain position in each repetition of the scan in real time. This tracking, inserted into a Gadgetron pipeline on a clinical scanner, allows updating the position of the field of view in a modified echo-planar imaging sequence. The method was evaluated in real-time in controlled-motion phantom experiments and ten fetal MR studies (17 + 4-34 + 3 gestational weeks) at 3T. The localization network was additionally tested retrospectively on 29 low-field (0.55T) datasets. RESULTS: Our method achieved real-time fetal head tracking and prospective correction of the acquisition geometry. Localization performance achieved Dice scores of 84.4% and 82.3%, respectively for both the unseen 1.5T/3T and 0.55T fetal data, with values higher for cephalic fetuses and increasing with gestational age. CONCLUSIONS: Our technique was able to follow the fetal brain even for fetuses under 18 weeks GA in real-time at 3T and was successfully applied "offline" to new cohorts on 0.55T. Next, it will be deployed to other modalities such as fetal diffusion MRI and to cohorts of pregnant participants diagnosed with pregnancy complications, for example, pre-eclampsia and congenital heart disease.

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.

Cortical morphology at birth reflects spatiotemporal patterns of gene expression in the fetal human brain.

Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal magnetic resonance imaging (MRI) in n = 292 healthy newborn infants (mean age at birth = 39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n = 156 samples from 16 brains, aged 12 to 37 postconceptional weeks [pcw]). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n = 64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis (PCA) of 6 measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated with estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons, and engaged in stem cell differentiation, neuron migration, and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.

Prenatal diagnosis of hypoplastic left heart syndrome on ultrasound using artificial intelligence: How does performance compare to a current screening programme?

BACKGROUND: Artificial intelligence (AI) has the potential to improve prenatal detection of congenital heart disease. We analysed the performance of the current national screening programme in detecting hypoplastic left heart syndrome (HLHS) to compare with our own AI model. METHODS: Current screening programme performance was calculated from local and national sources. AI models were trained using four-chamber ultrasound views of the fetal heart, using a ResNet classifier. RESULTS: Estimated current fetal screening programme sensitivity and specificity for HLHS were 94.3% and 99.985%, respectively. Depending on calibration, AI models to detect HLHS were either highly sensitive (sensitivity 100%, specificity 94.0%) or highly specific (sensitivity 93.3%, specificity 100%). Our analysis suggests that our highly sensitive model would generate 45,134 screen positive results for a gain of 14 additional HLHS cases. Our highly specific model would be associated with two fewer detected HLHS cases, and 118 fewer false positives. CONCLUSION: If used independently, our AI model performance is slightly worse than the performance level of the current screening programme in detecting HLHS, and this performance is likely to deteriorate further when used prospectively. This demonstrates that collaboration between humans and AI will be key for effective future clinical use.

Exploring a new paradigm for the fetal anomaly ultrasound scan: Artificial intelligence in real time.

OBJECTIVE: Advances in artificial intelligence (AI) have demonstrated potential to improve medical diagnosis. We piloted the end-to-end automation of the mid-trimester screening ultrasound scan using AI-enabled tools. METHODS: A prospective method comparison study was conducted. Participants had both standard and AI-assisted US scans performed. The AI tools automated image acquisition, biometric measurement, and report production. A feedback survey captured the sonographers' perceptions of scanning. RESULTS: Twenty-three subjects were studied. The average time saving per scan was 7.62 min (34.7%) with the AI-assisted method (p < 0.0001). There was no difference in reporting time. There were no clinically significant differences in biometric measurements between the two methods. The AI tools saved a satisfactory view in 93% of the cases (four core views only), and 73% for the full 13 views, compared to 98% for both using the manual scan. Survey responses suggest that the AI tools helped sonographers to concentrate on image interpretation by removing disruptive tasks. CONCLUSION: Separating freehand scanning from image capture and measurement resulted in a faster scan and altered workflow. Removing repetitive tasks may allow more attention to be directed identifying fetal malformation. Further work is required to improve the image plane detection algorithm for use in real time.

Maternal and fetal incidental findings on antenatal magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) examinations are increasingly used in antenatal clinical practice. Incidental findings are a recognized association with imaging and although in some circumstances their identification can alter management, they are often associated with increased anxiety, for both patient and clinician, as well as increased health care costs. OBJECTIVE: This study aimed to evaluate the incidence of unexpected findings in both the mother and fetus during antenatal MRI examinations. MATERIALS AND METHODS: A retrospective study was undertaken over a five-year period at St.. Thomas' Hospital in London. Maternal incidental findings were recorded from all clinical reports of all fetal MRIs performed (for clinical reasons and in healthy volunteers) during this period. Fetal incidental findings were recorded only in cases where women with uncomplicated pregnancies were participating as healthy volunteers. RESULTS: A total of 2,569 MRIs were included; 17% of women had maternal incidental findings. Of these, 1,099 were women with uncomplicated pregnancies who undertook research MRIs as healthy volunteers; fetal incidental findings were identified in 12.3%. CONCLUSION: Incidental findings are a common occurrence in antenatal MRI. Consideration should be given to counseling women appropriately before imaging and ensuring that robust local protocols are in place for follow-up and further management of such cases.

Complex diffusion-weighted image estimation via matrix recovery under general noise models.

We propose a patch-based singular value shrinkage method for diffusion magnetic resonance image estimation targeted at low signal to noise ratio and accelerated acquisitions. It operates on the complex data resulting from a sensitivity encoding reconstruction, where asymptotically optimal signal recovery guarantees can be attained by modeling the noise propagation in the reconstruction and subsequently simulating or calculating the limit singular value spectrum. Simple strategies are presented to deal with phase inconsistencies and optimize patch construction. The pertinence of our contributions is quantitatively validated on synthetic data, an in vivo adult example, and challenging neonatal and fetal cohorts. Our methodology is compared with related approaches, which generally operate on magnitude-only data and use data-based noise level estimation and singular value truncation. Visual examples are provided to illustrate effectiveness in generating denoised and debiased diffusion estimates with well preserved spatial and diffusion detail.

An exploration of the potential utility of fetal cardiovascular MRI as an adjunct to fetal echocardiography.

OBJECTIVES: Fetal cardiovascular magnetic resonance imaging (MRI) offers a potential alternative to echocardiography, although in practice, its use has been limited. We sought to explore the need for additional imaging in a tertiary fetal cardiology unit and the usefulness of standard MRI sequences. METHODS: Cases where the diagnosis was not fully resolved using echocardiography were referred for MRI. Following a three-plane localiser, fetal movement was assessed with a balanced steady-state free precession (bSSFP) cine. Single-shot fast spin echo and bSSFP sequences were used for diagnostic imaging. RESULTS: Twenty-two fetal cardiac MRIs were performed over 12 months, at mean gestation of 32 weeks (26-38 weeks). The majority of referrals were for suspected vascular abnormalities (17/22), particularly involving the aortic arch (n = 10) and pulmonary vessels (n = 4). Single-shot fast spin echo sequences produced 'black-blood' images, useful for examining the extracardiac vasculature in these cases. BSSFP sequences were more useful for intracardiac structures. Real-time SSFP allowed for dynamic assessment of structures such as cardiac masses, with enhancement patterns also allowing for tissue characterisation in these cases. CONCLUSIONS: Fetal vascular abnormalities such as coarctation can be difficult to diagnose by using ultrasound. Fetal MRI may have an adjunctive role in the evaluation of the extracardiac vascular anatomy and tissue characterisation. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Identification and characterisation of midbrain nuclei using optimised functional magnetic resonance imaging.

Localising activity in the human midbrain with conventional functional MRI (fMRI) is challenging because the midbrain nuclei are small and located in an area that is prone to physiological artefacts. Here we present a replicable and automated method to improve the detection and localisation of midbrain fMRI signals. We designed a visual fMRI task that was predicted would activate the superior colliculi (SC) bilaterally. A limited number of coronal slices were scanned, orientated along the long axis of the brainstem, whilst simultaneously recording cardiac and respiratory traces. A novel anatomical registration pathway was used to optimise the localisation of the small midbrain nuclei in stereotactic space. Two additional structural scans were used to improve registration between functional and structural T1-weighted images: an echo-planar image (EPI) that matched the functional data but had whole-brain coverage, and a whole-brain T2-weighted image. This pathway was compared to conventional registration pathways, and was shown to significantly improve midbrain registration. To reduce the physiological artefacts in the functional data, we estimated and removed structured noise using a modified version of a previously described physiological noise model (PNM). Whereas a conventional analysis revealed only unilateral SC activity, the PNM analysis revealed the predicted bilateral activity. We demonstrate that these methods improve the measurement of a biologically plausible fMRI signal. Moreover they could be used to investigate the function of other midbrain nuclei.

Magnetic resonance imaging of the newborn brain: manual segmentation of labelled atlases in term-born and preterm infants.

Premature birth is a major and growing problem. Investigations into neuroanatomical correlates and consequences of preterm birth are hampered by complex neonatal brain anatomy and unavailability of atlases and protocols covering the whole brain. We developed delineation protocols for the manual segmentation of cerebral magnetic resonance (MR) images from newborn infants into 50 regions with comprehensive coverage of the brain. We then segmented MR scans from 15 infants born preterm at median 29, range 26-35, weeks postmenstrual age and scanned at term-corrected age, and five term-born infants born at median 41, range 39-45, weeks postmenstrual age. Total and regional brain volumes were estimated in each infant, and regional volumes expressed as a fraction of total brain volume. Total brain volumes were higher with greater age at birth and at time of scan, but once corrected for age at scan there was no difference between preterm and term infants. Fractional age-corrected regional volumes were bigger unilaterally in terms in middle and inferior temporal gyri, anterior temporal lobe, fusiform gyrus and posterior cingulate gyrus. Fractional age-corrected regional volumes were larger in preterms bilaterally in hippocampus, amygdala, thalamus and lateral ventricles, left superior temporal gyrus and right caudate nucleus. These differences were not significant after correcting for multiple hypothesis testing, but suggest subtle differences between preterms and term-borns accessible to regional analysis. Detailed illustrated protocols are made available in the Appendix.

Disruption of intracardiac flow patterns in the newborn infant.

INTRODUCTION: Consistent patterns of rotational intracardiac flow have been demonstrated in the healthy adult human heart. Intracardiac rotational flow patterns are hypothesized to assist in the maintenance of kinetic energy of inflowing blood, augmenting cardiac function. Newborn cardiac function is known to be suboptimal secondary to decreased receptor number and sympathetic innervation, increased afterload, and increased reliance on atrial contraction to support ventricular filling. Patterns of intracardiac flow in the newborn have not previously been examined. RESULTS: Whereas 5 of the 13 infants studied showed significant evidence of rotational flow within the right atrium, 8 infants showed little or no rotational flow. Presence or absence of rotational flow was not related to gestational age, birth weight, postnatal age, atrial size, or image quality. Despite absence of intra-atrial rotational flow, atrioventricular valve flow into the left and right ventricles later in the cardiac cycle could be seen, suggesting that visualization techniques were adequate. DISCUSSION: While further study is required to assess its exact consequences on cardiac mechanics and energetics, disruption to intracardiac flow patterns could be another contributor to the multifactorial sequence that produces newborn circulatory failure. METHODS: We studied 13 newborn infants, using three-dimensional (3D) cardiac magnetic resonance phase-contrast imaging (spatial resolution 0.84 mm, temporal resolution 22.6 ms) performed without sedation/anesthesia.

PRETUS: A plug-in based platform for real-time ultrasound imaging research.

We present PRETUS - a Plugin-based Real Time UltraSound software platform for live ultrasound image analysis and operator support. The software is lightweight; functionality is brought in via independent plug-ins that can be arranged in sequence. The software allows to capture the real-time stream of ultrasound images from virtually any ultrasound machine, applies computational methods and visualizes the results on-the-fly. Plug-ins can run concurrently without blocking each other. They can be implemented in C++ and Python. A graphical user interface can be implemented for each plug-in, and presented to the user in a compact way. The software is free and open source, and allows for rapid prototyping and testing of real-time ultrasound imaging methods in a manufacturer-agnostic fashion. The software is provided with input, output and processing plug-ins, as well as with tutorials to illustrate how to develop new plug-ins for PRETUS.

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29.7 weeks), we combined Magnetic Resonance Imaging with a polygenic risk score (PRS) for five psychiatric pathologies to test the prediction that: deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness. The variance explained by the PRS in the relative volumes of four deep grey matter structures (caudate nucleus, thalamus, subthalamic nucleus and lentiform nucleus) was estimated using linear regression both for the full, mixed ancestral, cohort and a subsample of European infants. Psychiatric PRS was negatively associated with lentiform volume in the full cohort (ß = -0.24, p = 8 × 10-4) and a European subsample (ß = -0.24, p = 8 × 10-3). Genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress and are associated with neuroanatomic changes in the perinatal period.

Human-level Performance On Automatic Head Biometrics In Fetal Ultrasound Using Fully Convolutional Neural Networks.

Measurement of head biometrics from fetal ultrasonography images is of key importance in monitoring the healthy development of fetuses. However, the accurate measurement of relevant anatomical structures is subject to large inter-observer variability in the clinic. To address this issue, an automated method utilizing Fully Convolutional Networks (FCN) is proposed to determine measurements of fetal head circumference (HC) and biparietal diameter (BPD). An FCN was trained on approximately 2000 2D ultrasound images of the head with annotations provided by 45 different sonographers during routine screening examinations to perform semantic segmentation of the head. An ellipse is fitted to the resulting segmentation contours to mimic the annotation typically produced by a sonographer. The model's performance was compared with inter-observer variability, where two experts manually annotated 100 test images. Mean absolute model-expert error was slightly better than inter-observer error for HC (1.99mm vs 2.16mm), and comparable for BPD (0.61mm vs 0.59mm), as well as Dice coefficient (0.980 vs 0.980). Our results demonstrate that the model performs at a level similar to a human expert, and learns to produce accurate predictions from a large dataset annotated by many sonographers. Additionally, measurements are generated in near real-time at 15fps on a GPU, which could speed up clinical workflow for both skilled and trainee sonographers.

3-D Reconstruction in Canonical Co-Ordinate Space From Arbitrarily Oriented 2-D Images.

Limited capture range, and the requirement to provide high quality initialization for optimization-based 2-D/3-D image registration methods, can significantly degrade the performance of 3-D image reconstruction and motion compensation pipelines. Challenging clinical imaging scenarios, which contain significant subject motion, such as fetal in-utero imaging, complicate the 3-D image and volume reconstruction process. In this paper, we present a learning-based image registration method capable of predicting 3-D rigid transformations of arbitrarily oriented 2-D image slices, with respect to a learned canonical atlas co-ordinate system. Only image slice intensity information is used to perform registration and canonical alignment, no spatial transform initialization is required. To find image transformations, we utilize a convolutional neural network architecture to learn the regression function capable of mapping 2-D image slices to a 3-D canonical atlas space. We extensively evaluate the effectiveness of our approach quantitatively on simulated magnetic resonance imaging (MRI), fetal brain imagery with synthetic motion and further demonstrate qualitative results on real fetal MRI data where our method is integrated into a full reconstruction and motion compensation pipeline. Our learning based registration achieves an average spatial prediction error of 7 mm on simulated data and produces qualitatively improved reconstructions for heavily moving fetuses with gestational ages of approximately 20 weeks. Our model provides a general and computationally efficient solution to the 2-D/3-D registration initialization problem and is suitable for real-time scenarios.

Segmentation of brain MRI in young children.

RATIONALE AND OBJECTIVES: This article deals with an automatic tissue segmentation of brain magnetic resonance imaging (MRI) in young children. MATERIALS AND METHODS: We examine the suitability of state-of-the-art methods developed for the adult brain when applied to the segmentation of the brain MRI in young children. We develop a method of creation of a population-specific atlas in young children using a single manual segmentation. The method is based on nonlinear propagation of the segmentation into population and subsequent affine alignment into a reference space and averaging. RESULTS: Using this approach, we significantly improve the performance of the popular expectation-maximization algorithm on brain MRI in young children. The method can be used for building probabilistic atlases with any number of structures. We compare resulting algorithm with nonrigid registration-based label propagation. CONCLUSIONS: Finally, both methods are used to measure the volume of seven brain structures and measure the growth between 1 and 2 years of age.

Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

BACKGROUND: We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. METHODS AND FINDINGS: We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. CONCLUSIONS: Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

Artifact reduction using parallel imaging methods.

Multiple receiver coils produce images with different but complementary views of a patient. This can be used to shorten scans times but there often remain image artifacts caused by patient motion or physiological processes such as flowing blood. This paper reviews how the extra information from the multiple coils can be used to reduce image artifacts. In one method, affected portions of data can be identified and discarded but enough information is still available to reconstruct an improved image. In other methods, the motion itself is determined and the corrupted data is then corrected, leading to an image with reduced artifacts. Results are presented from images corrupted by motion or by flowing blood.

Common genetic variants and risk of brain injury after preterm birth.

BACKGROUND: The role of heritable factors in determining the common neurologic deficits seen after preterm birth is unknown, but the characteristic phenotype of neurocognitive, neuroanatomical, and growth abnormalities allows principled selection of candidate genes to test the hypothesis that common genetic variation modulates the risk for brain injury. METHODS: We collected an MRI-linked genomic DNA library from 83 preterm infants and genotyped tag single nucleotide polymorphisms in 13 relevant candidate genes. We used tract-based spatial statistics and deformation-based morphometry to examine the risks conferred by carriage of particular alleles at tag single nucleotide polymorphisms in a restricted number of genes and related these to the preterm cerebral endophenotype. RESULTS: Carriage of the minor allele at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene, which has been linked to neuronal migration and schizophrenia, and rs174576 in the fatty acid desaturase 2 gene, which encodes a rate-limiting enzyme for endogenous long chain polyunsaturated fatty acid synthesis and has been linked to intelligence, was associated with white matter abnormality measured in vivo using diffusion tensor imaging (P = .0009 and P = .0019, respectively). CONCLUSIONS: These results suggest that genetic variants modulate white matter injury after preterm birth, and known susceptibilities to neurologic status in later life may be exposed by the stress of premature exposure to the extrauterine environment.