Natural recovery of genetic diversity by gene flow in reforested areas of the endemic Canary Island pine, Pinus canariensis

The endemic pine, Pinus canariensis, forms one of the main forest ecosystems in the Canary Islands. In this archipelago, pine forest is a mosaic of natural stands (remnants of past forest overexploitation) and artificial stands planted from the 1940's. The genetic makeup of the artificially regenerated forest is of some concern. The use of reproductive material with uncontrolled origin or from a reduced number of parental trees may produce stands ill adapted to local conditions or unable to adapt in response to environmental change. The genetic diversity within a transect of reforested stands connecting two natural forest fragments has been studied with nuclear and chloroplast microsatellites. Little genetic differentiation and similar levels of genetic diversity to the surrounding natural stands were found for nuclear markers. However, chloroplast microsatellites presented lower haplotype diversity in reforested stands, and this may be a consequence of the lower effective population size of the chloroplast genome, meaning chloroplast markers have a higher sensitivity to bottlenecks. Understory natural regeneration within the reforestation was also analysed to study gene flow from natural forest into artificial stands. Estimates of immigration rate into artificially regenerated forest were high (0.68-0.75), producing a significant increase of genetic diversity (both in chloroplast and nuclear microsatellites), which indicates the capacity for genetic recovery for P. canariensis reforestations surrounded by larger natural stands

Spectral Graph Convolutions for Population-based Disease Prediction

Exploiting the wealth of imaging and non-imaging information for disease prediction tasks requires models capable of representing, at the same time, individual features as well as data associations between subjects from potentially large populations. Graphs provide a natural framework for such tasks, yet previous graph-based approaches focus on pairwise similarities without modelling the subjects' individual characteristics and features. On the other hand, relying solely on subject-specific imaging feature vectors fails to model the interaction and similarity between subjects, which can reduce performance. In this paper, we introduce the novel concept of Graph Convolutional Networks (GCN) for brain analysis in populations, combining imaging and non-imaging data. We represent populations as a sparse graph where its vertices are associated with image-based feature vectors and the edges encode phenotypic information. This structure was used to train a GCN model on partially labelled graphs, aiming to infer the classes of unlabelled nodes from the node features and pairwise associations between subjects. We demonstrate the potential of the method on the challenging ADNI and ABIDE databases, as a proof of concept of the benefit from integrating contextual information in classification tasks. This has a clear impact on the quality of the predictions, leading to 69.5% accuracy for ABIDE (outperforming the current state of the art of 66.8%) and 77% for ADNI for prediction of MCI conversion, significantly outperforming standard linear classifiers where only individual features are considered.Comment: International Conference on Medical Image Computing and Computer-Assisted Interventions (MICCAI) 201

A novel grading biomarker for the prediction of conversion from mild cognitive impairment to Alzheimer's disease

OBJECTIVE: Identifying mild cognitive impairment (MCI) subjects who will progress to Alzheimer's disease is not only crucial in clinical practice, but also has a significant potential to enrich clinical trials. The purpose of this study is to develop an effective biomarker for an accurate prediction of MCI-to-AD conversion from magnetic resonance (MR) images. METHODS: We propose a novel grading biomarker for the prediction of MCI-to-AD conversion. First, we comprehensively study the effects of several important factors on the performance in the prediction task including registration accuracy, age correction, feature selection and the selection of training data. Based on the studies of these factors, a grading biomarker is then calculated for each MCI subject using sparse representation techniques. Finally, the grading biomarker is combined with age and cognitive measures to provide a more accurate prediction of MCI-to-AD conversion. RESULTS: Using the ADNI dataset, the proposed global grading biomarker achieved an area under the receiver operating characteristic curve (AUC) in the range of 79%-81% for the prediction of MCI-to-AD conversion within 3 years in 10-fold cross validations. The classification AUC further increases to 84%-92% when age and cognitive measures are combined with the proposed grading biomarker. CONCLUSION: The obtained accuracy of the proposed biomarker benefits from the contributions of different factors: a tradeoff registration level to align images to the template space; the removal of the normal aging effect; selection of discriminative voxels; the calculation of the grading biomarker using AD and normal control groups; the integration of sparse representation technique and the combination of cognitive measures. SIGNIFICANCE: The evaluation on the ADNI dataset shows the efficacy of the proposed biomarker and demonstrates a significant contribution in accurate prediction of MCI-to-AD conversion

Road layout understanding by generative adversarial inpainting

Autonomous driving is becoming a reality, yet vehicles still need to rely on complex sensor fusion to understand the scene they act in. The ability to discern static environment and dynamic entities provides a comprehension of the road layout that poses constraints to the reasoning process about moving objects. We pursue this through a GAN-based semantic segmentation inpainting model to remove all dynamic objects from the scene and focus on understanding its static components such as streets, sidewalks and buildings. We evaluate this task on the Cityscapes dataset and on a novel synthetically generated dataset obtained with the CARLA simulator and specifically designed to quantitatively evaluate semantic segmentation inpaintings. We compare our methods with a variety of baselines working both in the RGB and segmentation domains

Efficient Multi-Scale 3D CNN with Fully Connected CRF for Accurate Brain Lesion Segmentation

We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the networks soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumors, and ischemic stroke. We improve on the state-of-the-art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available

Efficient multi-scale 3D CNN with fully connected CRF for accurate brain lesion segmentation

We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the network's soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumours, and ischemic stroke. We improve on the state-of-the-art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available.This work is supported by the EPSRC First Grant scheme (grant ref no. EP/N023668/1) and partially funded under the 7th Framework Programme by the European Commission (TBIcare: http: //www.tbicare.eu/ ; CENTER-TBI: https://www.center-tbi.eu/). This work was further supported by a Medical Research Council (UK) Program Grant (Acute brain injury: heterogeneity of mechanisms, therapeutic targets and outcome effects [G9439390 ID 65883]), the UK National Institute of Health Research Biomedical Research Centre at Cambridge and Technology Platform funding provided by the UK Department of Health. KK is supported by the Imperial College London PhD Scholarship Programme. VFJN is supported by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship. DKM is supported by an NIHR Senior Investigator Award. We gratefully acknowledge the support of NVIDIA Corporation with the donation of two Titan X GPUs for our research

Explainable Anatomical Shape Analysis through Deep Hierarchical Generative Models

Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer's disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging

Efficient Multi-Scale 3D CNN with Fully Connected CRF for Accurate Brain Lesion Segmentation

We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the network’s soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumors, and ischemic stroke. We improve on the state-of-theart for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly availabl

Robust whole-brain segmentation: Application to traumatic brain injury

We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to differentiate subjects with the presence of a mass lesion or midline shift from those with diffuse brain injury with 76.0% accuracy. The thalamus, putamen, pallidum and hippocampus are particularly affected. Their involvement predicts TBI disease progression.This work was partially funded under the 7th Framework Programme by the European Commission (http://cordis.europa.eu/ist/, TBIcare: http://www.tbicare.eu/, last accessed: 8 December 2014). The research was further supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. AH is supported by the Department of Health via the NIHR comprehensive BRC award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and Kings College Hospital NHS Foundation Trust. This work was further supported by a Medical Research Council (UK) Program Grant (Acute brain injury: heterogeneity of mechanisms, therapeutic targets and outcome effects [G9439390 ID 65883]), the UK National Institute of Health Research Biomedical Research Centre at Cambridge, the Technology Platform funding provided by the UK Department of Health and an EPSRC Pathways to Impact award. VFJN is supported by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship. DKM is supported by an NIHR Senior Investigator Award. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript

Sex. Dev.

Campomelic dysplasia (MIM 114290) is a severe malformation syndrome frequently accompanied by male-to-female sex reversal. Causative are mutations within the SOX9 gene on 17q24.3 as well as chromosomal aberrations (translocations, inversions or deletions) in the vicinity of SOX9 . Here, we report on a patient with muscular hypotonia, craniofacial dysmorphism, cleft palate, brachydactyly, malformations of thoracic spine, and gonadal dysgenesis with female external genitalia and müllerian duct derivatives in the presence of a male karyotype. X-ray examination and clinical examinations revealed no signs of campomelia. The combination of molecular cytogenetic analysis and array CGH revealed an unbalanced translocation between one chromosome 7 and one chromosome 17 [46,XY,t(7; 17)(q33;q24).ish t(7; 17) (wcp7+,wcp17+;wcp7+wcp17+)] with a deletion of approximately 4.2 Mb located about 0.5 Mb upstream of SOX9 . STS analysis confirmed the deletion of chromosome 17, which has occurred de novo on the paternal chromosome. The proximal breakpoint on chromosome 17 is localized outside the known breakpoint cluster regions. The deletion on chromosome 17q24 removes several genes. Among these genes PRKAR1A is deleted. Inactivating mutations of PRKAR1A cause Carney complex. To our knowledge, this is the first report of a patient with acampomelic campomelic dysplasia, carrying both a deletion and a translocation