Self-Supervised Ultrasound to MRI Fetal Brain Image Synthesis

Fetal brain magnetic resonance imaging (MRI) offers exquisite images of the developing brain but is not suitable for second-trimester anomaly screening, for which ultrasound (US) is employed. Although expert sonographers are adept at reading US images, MR images which closely resemble anatomical images are much easier for non-experts to interpret. Thus in this paper we propose to generate MR-like images directly from clinical US images. In medical image analysis such a capability is potentially useful as well, for instance for automatic US-MRI registration and fusion. The proposed model is end-to-end trainable and self-supervised without any external annotations. Specifically, based on an assumption that the US and MRI data share a similar anatomical latent space, we first utilise a network to extract the shared latent features, which are then used for MRI synthesis. Since paired data is unavailable for our study (and rare in practice), pixel-level constraints are infeasible to apply. We instead propose to enforce the distributions to be statistically indistinguishable, by adversarial learning in both the image domain and feature space. To regularise the anatomical structures between US and MRI during synthesis, we further propose an adversarial structural constraint. A new cross-modal attention technique is proposed to utilise non-local spatial information, by encouraging multi-modal knowledge fusion and propagation. We extend the approach to consider the case where 3D auxiliary information (e.g., 3D neighbours and a 3D location index) from volumetric data is also available, and show that this improves image synthesis. The proposed approach is evaluated quantitatively and qualitatively with comparison to real fetal MR images and other approaches to synthesis, demonstrating its feasibility of synthesising realistic MR images.Comment: IEEE Transactions on Medical Imaging 202

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2 , selected using World Health Organization recommendations for growth standards3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5 . The atlas was produced using 1,059 optimal quality, three dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8 . The atlas corresponds structurally to published magnetic resonance images9 , but with finer anatomical details in deep grey matter. The between study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks’ gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks’ gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment

The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm

Objectives: Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. Methods: We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. Results: A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (−3.8 days, 95%CI [−5.5; −2.0], P = <.001) and low (−4.0 days, 95% CI [−6.7; −1.2] P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (−4.4 days, 95%CI [−6.4; −2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. Conclusion: The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm

Introduction: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. Material and methods: Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. Results: In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P =.002). Conclusions: This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester