Maturational networks of human fetal brain activity reveal emerging connectivity patterns prior to ex-utero exposure.

A key feature of the fetal period is the rapid emergence of organised patterns of spontaneous brain activity. However, characterising this process in utero using functional MRI is inherently challenging and requires analytical methods which can capture the constituent developmental transformations. Here, we introduce a novel analytical framework, termed "maturational networks" (matnets), that achieves this by modelling functional networks as an emerging property of the developing brain. Compared to standard network analysis methods that assume consistent patterns of connectivity across development, our method incorporates age-related changes in connectivity directly into network estimation. We test its performance in a large neonatal sample, finding that the matnets approach characterises adult-like features of functional network architecture with a greater specificity than a standard group-ICA approach; for example, our approach is able to identify a nearly complete default mode network. In the in-utero brain, matnets enables us to reveal the richness of emerging functional connections and the hierarchy of their maturational relationships with remarkable anatomical specificity. We show that the associative areas play a central role within prenatal functional architecture, therefore indicating that functional connections of high-level associative areas start emerging prior to exposure to the extra-utero environment.

Accurate segmentation of neonatal brain MRI with deep learning.

An important step toward delivering an accurate connectome of the human brain is robust segmentation of 3D Magnetic Resonance Imaging (MRI) scans, which is particularly challenging when carried out on perinatal data. In this paper, we present an automated, deep learning-based pipeline for accurate segmentation of tissues from neonatal brain MRI and extend it by introducing an age prediction pathway. A major constraint to using deep learning techniques on developing brain data is the need to collect large numbers of ground truth labels. We therefore also investigate two practical approaches that can help alleviate the problem of label scarcity without loss of segmentation performance. First, we examine the efficiency of different strategies of distributing a limited budget of annotated 2D slices over 3D training images. In the second approach, we compare the segmentation performance of pre-trained models with different strategies of fine-tuning on a small subset of preterm infants. Our results indicate that distributing labels over a larger number of brain scans can improve segmentation performance. We also show that even partial fine-tuning can be superior in performance to a model trained from scratch, highlighting the relevance of transfer learning strategies under conditions of label scarcity. We illustrate our findings on large, publicly available T1- and T2-weighted MRI scans (n = 709, range of ages at scan: 26-45 weeks) obtained retrospectively from the Developing Human Connectome Project (dHCP) cohort.

A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features.

Cardiovascular diseases are a public health concern; they remain the leading cause of morbidity and mortality in patients with type 2 diabetes. Phenotypic information available from retinal fundus images and clinical measurements, in addition to genomic data, can identify relevant biomarkers of cardiovascular health. In this study, we assessed whether such biomarkers stratified risks of major adverse cardiac events (MACE). A retrospective analysis was carried out on an extract from the Tayside GoDARTS bioresource of participants with type 2 diabetes (n = 3,891). A total of 519 features were incorporated, summarising morphometric properties of the retinal vasculature, various single nucleotide polymorphisms (SNPs), as well as routine clinical measurements. After imputing missing features, a predictive model was developed on a randomly sampled set (n = 2,918) using L1-regularised logistic regression (lasso). The model was evaluated on an independent set (n = 973) and its performance associated with overall hazard rate after censoring (log-rank p < 0.0001), suggesting that multimodal features were able to capture important knowledge for MACE risk assessment. We further showed through a bootstrap analysis that all three sources of information (retinal, genetic, routine clinical) offer robust signal. Particularly robust features included: tortuousity, width gradient, and branching point retinal groupings; SNPs known to be associated with blood pressure and cardiovascular phenotypic traits; age at imaging; clinical measurements such as blood pressure and high density lipoprotein. This novel approach could be used for fast and sensitive determination of future risks associated with MACE.

Radiomics in paediatric neuro-oncology: A multicentre study on MRI texture analysis.

Brain tumours are the most common solid cancers in children in the UK and are the most common cause of cancer deaths in this age group. Despite current advances in MRI, non-invasive diagnosis of paediatric brain tumours has yet to find its way into routine clinical practice. Radiomics, the high-throughput extraction and analysis of quantitative image features (e.g. texture), offers potential solutions for tumour characterization and decision support. In the search for diagnostic oncological markers, the primary aim of this work was to study the application of MRI texture analysis (TA) for the classification of paediatric brain tumours. A multicentre study was carried out, within a supervised classification framework, on clinical MR images, and a support vector machine (SVM) was trained with 3D textural attributes obtained from conventional MRI. To determine the cross-centre transferability of TA, an assessment of how SVM performs on unseen datasets was carried out through rigorous pairwise testing. The study also investigated the nature of features that are most likely to train classifiers that can generalize well with the data. Finally, the issue of class imbalance, which arises due to some tumour types being more common than others, was explored. For each of the tests carried out through pairwise testing, the optimal area under the receiver operating characteristic curve ranged between 76% and 86%, suggesting that the model was able to capture transferable tumour information. Feature selection results suggest that similar aspects of tumour texture are enhanced by MR images obtained at different hospitals. Our results also suggest that the availability of equally represented classes has enabled SVM to better characterize the data points. The findings of the study presented here support the use of 3D TA on conventional MR images to aid diagnostic classification of paediatric brain tumours.

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.

Three-dimensional textural features of conventional MRI improve diagnostic classification of childhood brain tumours.

The aim of this study was to assess the efficacy of three-dimensional texture analysis (3D TA) of conventional MR images for the classification of childhood brain tumours in a quantitative manner. The dataset comprised pre-contrast T1 - and T2-weighted MRI series obtained from 48 children diagnosed with brain tumours (medulloblastoma, pilocytic astrocytoma and ependymoma). 3D and 2D TA were carried out on the images using first-, second- and higher order statistical methods. Six supervised classification algorithms were trained with the most influential 3D and 2D textural features, and their performances in the classification of tumour types, using the two feature sets, were compared. Model validation was carried out using the leave-one-out cross-validation (LOOCV) approach, as well as stratified 10-fold cross-validation, in order to provide additional reassurance. McNemar's test was used to test the statistical significance of any improvements demonstrated by 3D-trained classifiers. Supervised learning models trained with 3D textural features showed improved classification performances to those trained with conventional 2D features. For instance, a neural network classifier showed 12% improvement in area under the receiver operator characteristics curve (AUC) and 19% in overall classification accuracy. These improvements were statistically significant for four of the tested classifiers, as per McNemar's tests. This study shows that 3D textural features extracted from conventional T1 - and T2-weighted images can improve the diagnostic classification of childhood brain tumours. Long-term benefits of accurate, yet non-invasive, diagnostic aids include a reduction in surgical procedures, improvement in surgical and therapy planning, and support of discussions with patients' families. It remains necessary, however, to extend the analysis to a multicentre cohort in order to assess the scalability of the techniques used.

3D Texture Analysis of Heterogeneous MRI Data for Diagnostic Classification of Childhood Brain Tumours.

Brain tumours are the most frequently occuring solid tumours affecting childhood, representing 27% of all cancers. The most common posterior fossa tumours are medulloblastoma, pilocytic astrocytoma and ependymoma. Texture Analysis (TA) of Magnetic Resonance Imaging (MRI) aims to represent pixel distributions, intensities and dependencies using mathematically defined features. Such features could potentially provide quantifiable information that is beyond the human vision capabilities, and hence be used to supplement qualitative assessments conducted by radiologists. The primary aim of this study was to carry out a multicentre investigation on the efficacy of 3D TA for diagnostic classification of childhood brain tumours, using conventional MRI images. The data used had been acquired at three different hospitals and consisted of pre-contrast T1 and T2-weighted MRI series, obtained from 121 children diagnosed with medulloblastoma, pilocytic astrocytoma and ependymoma. Using 3D textural features, based on first, second and higher order statistical methods, a support vector machine (SVM) classifier was trained and tested using the leave-one-out cross-validation (LOOCV) approach. An essential outcome of this study is that 3D TA demonstrated a good overall performance, when used on data acquired from a number of centres and using scanners made by different manufacturers and at different magnetic field strengths.

An Extensible Neuroimaging e-Repository for Clinical Trials of Paediatric Brain Tumours.

Novel imaging techniques are playing an increasing role in tumour characterisation, assessment and management. However, incorporating imaging data into clinical trials presents a number of challenges in terms of quality control, standardisation in data collection, interoperability of widely used archiving systems and extensibility of imaging software architectures. Additionally, currently available monolithic applications cannot fulfil the diverse and rapidly changing needs of the clinical imaging research community. This paper discusses the limitations of the current CCLG Remote Data Entry (RDE) system and introduces the prototype of an alternative modular system based on the Extensible Neuroimaging Archive Toolkit (XNAT). The modular nature of the presented prototype promotes incremental software evolution and allows for flexible system customisation to suit the needs of individual imaging centres.

#DigitalHealth: Exploring Users' Perspectives through Social Media Analysis.

In order to explore the role of social media in forming an understanding of digital healthcare, we conducted a study involving sentiment and network analysis of Twitter contents. In doing this, we gathered 20,400 tweets that mentioned the key term #DigitalHealth for 55 hours, over a three-day period. In addition to examining users' opinions through sentiment analysis, we calculated in-degree centralities of nodes to identify the hubs in the network of interactions. The results suggest that the overall opinion about digital healthcare is generally positive. Additionally, our findings indicate that the most prevalent keywords, associated with digital health, widely range from mobile health to wearable technologies and big data. Surprisingly, the results show that the newly announced wearable technologies could occupy the majority of discussions.

3D texture analysis of MR images to improve classification of paediatric brain tumours: a preliminary study.

Brain and central nervous system (CNS) tumours form the second most common group of cancers in children in the UK, accounting for 27% of all childhood cancers. Initial assessment of tumours from MRI scans is usually performed qualitatively, via radiologists' visual inspection. However, different brain tumours do not always demonstrate clear differences in physical appearance, so a diagnosis is usually made via histopathological examination of biopsy samples taken through surgery. This gives rise to the need for accurate, yet non-invasive diagnostic aids. In a previous study, we demonstrated the potential of MRI texture analysis in capturing quantitative information about paediatric brain tumours. In this work, we carry out a preliminary investigation on the use of 3D (volumetric) texture analysis of T1 and T2-weighted MR images in order to classify paediatric brain tumours. We then compare its performance with the traditional 2D texture analysis approach. Our preliminary findings are very encouraging and show that 3D textural features are capable of capturing more discriminative information about the tumours than the traditional 2D approach. However, it remains necessary to expand the work further to include larger cohorts and additional modalities.

MRI texture analysis in paediatric oncology: a preliminary study.

Despite current advances in neuro-imaging, the characterisation of paediatric brain tumours and neurological disorders is very challenging. Whilst Magnetic Resonance Imaging (MRI) provides images of superb clarity, it gives little information on how aggressive a tumour is. It is also very difficult to visually inspect any underlying textural patterns between tumours on MR images. This gives rise to the need for a quantitative means of analysing MR images for characterising tumours. In this work, we present a preliminary investigation into the effectiveness of texture analysis as a quantitative approach for classifying paediatric brain tumours.