Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.

OBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD

Machine learning for efficient recognition of anatomical structures and abnormalities in biomedical images

Three studies have been carried out to investigate new approaches to efficient image segmentation and anomaly detection. The first study investigates the use of deep learning in patch based segmentation. Current approaches to patch based segmentation use low level features such as the sum of squared differences between patches. We argue that better segmentation can be achieved by harnessing the power of deep neural networks. Currently these networks make extensive use of convolutional layers. However, we argue that in the context of patch based segmentation, convolutional layers have little advantage over the canonical artificial neural network architecture. This is because a patch is small, and does not need decomposition and thus will not benefit from convolution. Instead, we make use of the canonical architecture in which neurons only compute dot products, but also incorporate modern techniques of deep learning. The resulting classifier is much faster and less memory-hungry than convolution based networks. In a test application to the segmentation of hippocampus in human brain MR images, we significantly outperformed prior art with a median Dice score up to 90.98% at a near real-time speed (<1s). The second study is an investigation into mouse phenotyping, and develops a high-throughput framework to detect morphological abnormality in mouse embryo micro-CT images. Existing work in this line is centred on, either the detection of phenotype-specific features or comparative analytics. The former approach lacks generality and the latter can often fail, for example, when the abnormality is not associated with severe volume variation. Both these approaches often require image segmentation as a pre-requisite, which is very challenging when applied to embryo phenotyping. A new approach to this problem in which non-rigid registration is combined with robust principal component analysis (RPCA), is proposed. The new framework is able to efficiently perform abnormality detection in a batch of images. It is sensitive to both volumetric and non-volumetric variations, and does not require image segmentation. In a validation study, it successfully distinguished the abnormal VSD and polydactyly phenotypes from the normal, respectively, at 85.19% and 88.89% specificities, with 100% sensitivity in both cases. The third study investigates the RPCA technique in more depth. RPCA is an extension of PCA that tolerates certain levels of data distortion during feature extraction, and is able to decompose images into regular and singular components. It has previously been applied to many computer vision problems (e.g. video surveillance), attaining excellent performance. However these applications commonly rest on a critical condition: in the majority of images being processed, there is a background with very little variation. By contrast in biomedical imaging there is significant natural variation across different images, resulting from inter-subject variability and physiological movements. Non-rigid registration can go some way towards reducing this variance, but cannot eliminate it entirely. To address this problem we propose a modified framework (RPCA-P) that is able to incorporate natural variation priors and adjust outlier tolerance locally, so that voxels associated with structures of higher variability are compensated with a higher tolerance in regularity estimation. An experimental study was applied to the same mouse embryo micro-CT data, and notably improved the detection specificity to 94.12% for the VSD and 90.97% for the polydactyly, while maintaining the sensitivity at 100%.Open Acces

Three-dimensional anatomical atlas of the human body

A thesis submitted in partial fulfillment of the requirements for the degree of Doctor in Information Management, specialization in Geographic Information SystemsAnatomical atlases allow mapping the anatomical structures of the human body. Early versions of these systems consisted of analogic representations with informative text and labelled images of the human body. With the advent of computer systems, digital versions emerged and the third dimension was introduced. Consequently, these systems increased their efficiency, allowing more realistic visualizations with improved interactivity. The development of anatomical atlases in geographic information systems (GIS) environments allows the development of platforms with a high degree of interactivity and with tools to explore and analyze the human body. In this thesis, a prototype for the human body representation is developed. The system includes a 3D GIS topological model, a graphical user interface and functions to explore and analyze the interior and the surface of the anatomical structures of the human body. The GIS approach relies essentially on the topological characteristics of the model and on the kind of available functions, which include measurement, identification, selection and analysis. With the incorporation of these functions, the final system has the ability to replicate the kind of information provided by the conventional anatomical atlases and also provides a higher level of functionality, since some of the atlases limitations are precisely features offered by GIS, namely, interactive capabilities, multilayer management, measurement tools, edition mode, allowing the expansion of the information contained in the system, and spatial analyzes

Deep learning based pipeline for fingerprinting using brain functional MRI connectivity data

In this work we describe an appropriate pipeline for using deep-learning as a form of improving the brain functional connectivity-based fingerprinting process which is based in functional Magnetic Resonance Imaging (fMRI) data-processing results. This pipeline approach is mostly intended for neuroscientists, biomedical engineers, and physicists that are looking for an easy form of using fMRI-based Deep-Learning in identifying people, drastic brain alterations in those same people, and/or pathologic consequences to people’s brains. Computer scientists and engineers can also gain by noticing the data-processing improvements obtained by using the here-proposed pipeline. With our best approach, we obtained an average accuracy of 0.3132 ± 0.0129 and an average validation cost of 3.1422 ± 0.0668, which clearly outperformed the published Pearson correlation approach performance with a 50 Nodes parcellation which had an accuracy of 0.237.Thanks to Eduarda Sousa for support. NFL was supported by a fellowship of the project MEDPERSYST - POCI-01-0145-FEDER-016428, funded by Portugal’s FCT. This work was also supported by NORTE-01-0145-FEDER-000013, and NORTE 2020 under the Portugal 2020 Partnership Agreement through the FEDER, plus it was funded by the European Commission (FP7) “SwitchBox - Maintaining health in old age through homeostasis” (Contract HEALTH-F2-2010-259772), and co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte), under the QREN through FEDER, and by the “Fundação Calouste Gulbenkian” (Portugal) (Contract grant number: P-139977; project “TEMPO - Better mental health during ageing based on temporal prediction of individual brain ageing trajectories”). We gratefully acknowledge the support of the NVIDIA Corporation with their donation of a Quadro P6000 board used in this research. This work was also supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT within the Project Scope: UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

Smart Cage Active Contours and their application to brain image segmentation

In this work we present a new segmentation method named Smart Cage Active Contours (SCAC) that combines a parametrized active contour framework named Cage Active Contours (CAC), based on a ne trans- formations, with Active Shape Models (ASM). Our method e ectively restricts the shapes the evolving contours can take without the need of the training images to be manually landmarked. We apply our method to segment the caudate nuclei subcortical structure of a set of 40 subjects in magnetic resonance brain images, with promising results

QUINT: Workflow for Quantification and Spatial Analysis of Features in Histological Images From Rodent Brain

Transgenic animal models are invaluable research tools for elucidating the pathways and mechanisms involved in the development of neurodegenerative diseases. Mechanistic clues can be revealed by applying labelling techniques such as immunohistochemistry or in situ hybridisation to brain tissue sections. Precision in both assigning anatomical location to the sections and quantifying labelled features is crucial for output validity, with a stereological approach or image-based feature extraction typically used. However, both approaches are restricted by the need to manually delineate anatomical regions. To circumvent this limitation, we present the QUINT workflow for quantification and spatial analysis of labelling in series of rodent brain section images based on available 3D reference atlases. The workflow is semi-automated, combining three open source software that can be operated without scripting knowledge, making it accessible to most researchers. As an example, a brain region-specific quantification of amyloid plaques across whole transgenic Tg2576 mouse brain series, immunohistochemically labelled for three amyloid-related antigens is demonstrated. First, the whole brain image series were registered to the Allen Mouse Brain Atlas to produce customised atlas maps adapted to match the cutting plan and proportions of the sections (QuickNII software). Second, the labelling was segmented from the original images by the Random Forest Algorithm for supervised classification (ilastik software). Finally, the segmented images and atlas maps were used to generate plaque quantifications for each region in the reference atlas (Nutil software). The method yielded comparable results to manual delineations and to the output of a stereological method. While the use case demonstrates the QUINT workflow for quantification of amyloid plaques only, the workflow is suited to all mouse or rat brain series with labelling that is visually distinct from the background, for example for the quantification of cells or labelled proteins

Hippocampal subfields at ultra high field MRI: An overview of segmentation and measurement methods

The hippocampus is one of the most interesting and studied brain regions because of its involvement in memory functions and its vulnerability in pathological conditions, such as neurodegenerative processes. In the recent years, the increasing availability of Magnetic Resonance Imaging (MRI) scanners that operate at ultra-high field (UHF), that is, with static magnetic field strength ≥7T, has opened new research perspectives. Compared to conventional high-field scanners, these systems can provide new contrasts, increased signal-to-noise ratio and higher spatial resolution, thus they may improve the visualization of very small structures of the brain, such as the hippocampal subfields. Studying the morphometry of the hippocampus is crucial in neuroimaging research because changes in volume and thickness of hippocampal subregions may be relevant in the early assessment of pathological cognitive decline and Alzheimer's Disease (AD). The present review provides an overview of the manual, semi-automated and fully automated methods that allow the assessment of hippocampal subfield morphometry at UHF MRI, focusing on the different hippocampal segmentation produced. © 2017 Wiley Periodicals, Inc