Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth.

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multimodal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared with term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.

BOUNTI: Brain vOlumetry and aUtomated parcellatioN for 3D feTal MRI.

Fetal MRI is widely used for quantitative brain volumetry studies. However, currently, there is a lack of universally accepted protocols for fetal brain parcellation and segmentation. Published clinical studies tend to use different segmentation approaches that also reportedly require significant amounts of time-consuming manual refinement. In this work, we propose to address this challenge by developing a new robust deep learning-based fetal brain segmentation pipeline for 3D T2w motion corrected brain images. At first, we defined a new refined brain tissue parcellation protocol with 19 regions-of-interest using the new fetal brain MRI atlas from the Developing Human Connectome Project. This protocol design was based on evidence from histological brain atlases, clear visibility of the structures in individual subject 3D T2w images and the clinical relevance to quantitative studies. It was then used as a basis for developing an automated deep learning brain tissue parcellation pipeline trained on 360 fetal MRI datasets with different acquisition parameters using semi-supervised approach with manually refined labels propagated from the atlas. The pipeline demonstrated robust performance for different acquisition protocols and GA ranges. Analysis of tissue volumetry for 390 normal participants (21-38 weeks gestational age range), scanned with three different acquisition protocols, did not reveal significant differences for major structures in the growth charts. Only minor errors were present in < 15% of cases thus significantly reducing the need for manual refinement. In addition, quantitative comparison between 65 fetuses with ventriculomegaly and 60 normal control cases were in agreement with the findings reported in our earlier work based on manual segmentations. These preliminary results support the feasibility of the proposed atlas-based deep learning approach for large-scale volumetric analysis. The created fetal brain volumetry centiles and a docker with the proposed pipeline are publicly available online at https://hub.docker.com/r/fetalsvrtk/segmentation (tag brain_bounti_tissue).

Structural and functional asymmetry of the neonatal cerebral cortex.

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Here we investigated cortical asymmetries in 442 healthy term-born neonates using structural and functional magnetic resonance images from the Developing Human Connectome Project. Our results demonstrate that the neonatal cortex is markedly asymmetric in both structure and function. Cortical asymmetries observed in the term cohort were contextualized in two ways: by comparing them against cortical asymmetries observed in 103 preterm neonates scanned at term-equivalent age, and by comparing structural asymmetries against those observed in 1,110 healthy young adults from the Human Connectome Project. While associations with preterm birth and biological sex were minimal, significant differences exist between birth and adulthood.

The Multiscale Surface Vision Transformer.

Surface meshes are a favoured domain for representing structural and functional information on the human cortex, but their complex topology and geometry pose significant challenges for deep learning analysis. While Transformers have excelled as domain-agnostic architectures for sequence-to-sequence learning, notably for structures where the translation of the convolution operation is non-trivial, the quadratic cost of the self-attention operation remains an obstacle for many dense prediction tasks. Inspired by some of the latest advances in hierarchical modelling with vision transformers, we introduce the Multiscale Surface Vision Transformer (MS-SiT) as a backbone architecture for surface deep learning. The self-attention mechanism is applied within local-mesh-windows to allow for high-resolution sampling of the underlying data, while a shifted-window strategy improves the sharing of information between windows. Neighbouring patches are successively merged, allowing the MS-SiT to learn hierarchical representations suitable for any prediction task. Results demonstrate that the MS-SiT outperforms existing surface deep learning methods for neonatal phenotyping prediction tasks using the Developing Human Connectome Project (dHCP) dataset. Furthermore, building the MS-SiT backbone into a U-shaped architecture for surface segmentation demonstrates competitive results on cortical parcellation using the UK Biobank (UKB) and manually-annotated MindBoggle datasets. Code and trained models are publicly available at https://github.com/metrics-lab/surface-vision-transformers.

Telomere length and brain imaging phenotypes in UK Biobank.

Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker of biological aging. Short telomeres are associated with an increased risk of neurological and psychiatric disorders including dementia. The mechanism underlying this risk is unclear, and may involve brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized. Here we show that leucocyte telomere length (LTL) is associated with multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL is associated with: i) larger global and subcortical grey matter volumes including the hippocampus, ii) lower T1-weighted grey-white tissue contrast in sensory cortices, iii) white-matter microstructure measures in corpus callosum and association fibres, iv) lower volume of white matter hyperintensities, and v) lower basal ganglia iron. Longer LTL was protective against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91-0.96), but not stroke or Parkinson's disease. LTL is associated with multiple MRI endophenotypes of neurodegenerative disease, suggesting a pathway by which longer LTL may confer protective against dementia.

ICAM-Reg: Interpretable Classification and Regression With Feature Attribution for Mapping Neurological Phenotypes in Individual Scans.

An important goal of medical imaging is to be able to precisely detect patterns of disease specific to individual scans; however, this is challenged in brain imaging by the degree of heterogeneity of shape and appearance. Traditional methods, based on image registration, historically fail to detect variable features of disease, as they utilise population-based analyses, suited primarily to studying group-average effects. In this paper we therefore take advantage of recent developments in generative deep learning to develop a method for simultaneous classification, or regression, and feature attribution (FA). Specifically, we explore the use of a VAE-GAN (variational autoencoder - general adversarial network) for translation called ICAM, to explicitly disentangle class relevant features, from background confounds, for improved interpretability and regression of neurological phenotypes. We validate our method on the tasks of Mini-Mental State Examination (MMSE) cognitive test score prediction for the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, as well as brain age prediction, for both neurodevelopment and neurodegeneration, using the developing Human Connectome Project (dHCP) and UK Biobank datasets. We show that the generated FA maps can be used to explain outlier predictions and demonstrate that the inclusion of a regression module improves the disentanglement of the latent space. Our code is freely available on GitHub https://github.com/CherBass/ICAM.

A bipolar taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients.

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (N=34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bipolar distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex; complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (N=228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age.

INTRODUCTION: The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. METHODS: We sought to first map typical cortical micro- and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n = 259). Then we offer a comprehensive characterization of the cortical consequences of preterm birth in 76 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. RESULTS: In the term-born neonatal brain, we observed heterogeneous and regionally specific associations between age at scan and measures of cortical morphology and microstructure, including rapid surface expansion, greater cortical thickness, lower cortical anisotropy and higher neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. CONCLUSION: We showed that preterm birth alters cortical micro- and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

Positive Inotropic Effect of Prostaglandin F2α in Rat Ventricular Trabeculae.

Prostaglandins are ubiquitous signaling molecules in the body that produce autocrine/paracrine effects on target cells in response to mechanical or chemical signals. In the heart, long-term exposure to prostaglandin (PG) F2α has been linked to the development of hypertrophy; however, there is no consensus on the acute effect of PGF2α. Our aim was to determine the response to exogenous PGF2α in isolated trabeculae from rat hearts. PGF2α (1 µM) increased both the Ca transients and the isometric stress in trabeculae, reaching steady state after 10-15 minutes, without altering the time course of Ca transient decay. The precursor of PGF2α, arachidonic acid, also stimulated a similar response. The positive inotropic effect of PGF2α was mediated through a protein kinase C signaling pathway that involved activation of the sarcolemmal Na/H exchanger. We also found that the slow force response to stretch was attenuated in the presence of PGF2α and by addition of indomethacin, a blocker of prostaglandin synthesis. In conclusion, PGF2α was positively inotropic when acutely applied to trabeculae and contributed to the increased Ca transients during the slow force response to stretch. Together, these data suggest that PGF2α is important in maintaining homeostasis during volume loading in healthy hearts.