Towards segmentation and spatial alignment of the human embryonic brain using deep learning for atlas-based registration

We propose an unsupervised deep learning method for atlas based registration to achieve segmentation and spatial alignment of the embryonic brain in a single framework. Our approach consists of two sequential networks with a specifically designed loss function to address the challenges in 3D first trimester ultrasound. The first part learns the affine transformation and the second part learns the voxelwise nonrigid deformation between the target image and the atlas. We trained this network end-to-end and validated it against a ground truth on synthetic datasets designed to resemble the challenges present in 3D first trimester ultrasound. The method was tested on a dataset of human embryonic ultrasound volumes acquired at 9 weeks gestational age, which showed alignment of the brain in some cases and gave insight in open challenges for the proposed method. We conclude that our method is a promising approach towards fully automated spatial alignment and segmentation of embryonic brains in 3D ultrasound

BigBrain 3D atlas of cortical layers: Cortical and laminar thickness gradients diverge in sensory and motor cortices.

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy

Creation of Computerized 3D MRI-Integrated Atlases of the Human Basal Ganglia and Thalamus

Functional brain imaging and neurosurgery in subcortical areas often requires visualization of brain nuclei beyond the resolution of current magnetic resonance imaging (MRI) methods. We present techniques used to create: (1) a lower resolution 3D atlas, based on the Schaltenbrand and Wahren print atlas, which was integrated into a stereotactic neurosurgery planning and visualization platform (VIPER); and (2) a higher resolution 3D atlas derived from a single set of manually segmented histological slices containing nuclei of the basal ganglia, thalamus, basal forebrain, and medial temporal lobe. Both atlases were integrated to a canonical MRI (Colin27) from a young male participant by manually identifying homologous landmarks. The lower resolution atlas was then warped to fit the MRI based on the identified landmarks. A pseudo-MRI representation of the high-resolution atlas was created, and a non-linear transformation was calculated in order to match the atlas to the template MRI. The atlas can then be warped to match the anatomy of Parkinson's disease surgical candidates by using 3D automated non-linear deformation methods. By way of functional validation of the atlas, the location of the sensory thalamus was correlated with stereotactic intraoperative physiological data. The position of subthalamic electrode positions in patients with Parkinson's disease was also evaluated in the atlas-integrated MRI space. Finally, probabilistic maps of subthalamic stimulation electrodes were developed, in order to allow group analysis of the location of contacts associated with the best motor outcomes. We have therefore developed, and are continuing to validate, a high-resolution computerized MRI-integrated 3D histological atlas, which is useful in functional neurosurgery, and for functional and anatomical studies of the human basal ganglia, thalamus, and basal forebrain

Mapping sheep to human brain: The need for a sheep brain atlas

A brain atlas is essential for understanding the anatomical relationship between neuroanatomical structures. Standard stereotaxic coordinates and reference systems have been developed for humans, non-human primates and small laboratory animals to contribute to translational neuroscience research. Despite similar neuroanatomical and neurofunctional features between the sheep and human brain, little is known of the sheep brain stereotaxy, and a detailed sheep atlas is scarce. Here, we briefly discuss the value of using sheep in neurological research and the paucity of literature concerning the coordinates system during neurosurgical approaches. Recent advancements such as computerized tomography, positron emission tomography, magnetic resonance imaging, functional magnetic resonance imaging and diffusion tensor imaging are used for targeting and localizing the coordinates and brain areas in humans. Still, their application in sheep is rare due to the lack of a 3D stereotaxic sheep atlas by which to map sheep brain structures to its human counterparts. More recently, a T1- and T2-weighted high-resolution MRI 3D stereotaxic atlas of the sheep brain has been generated, however, the journey to create a sheep brain atlas by which to map directly to the human brain is still uncharted. Therefore, developing a detailed sheep brain atlas is valuable for the future to facilitate the use of sheep as a large animal experimental non-primate model for translational neurological research

Atlas-Guided Segmentation of Vervet Monkey Brain MRI

The vervet monkey is an important nonhuman primate model that allows the study of isolated environmental factors in a controlled environment. Analysis of monkey MRI often suffers from lower quality images compared with human MRI because clinical equipment is typically used to image the smaller monkey brain and higher spatial resolution is required. This, together with the anatomical differences of the monkey brains, complicates the use of neuroimage analysis pipelines tuned for human MRI analysis. In this paper we developed an open source image analysis framework based on the tools available within the 3D Slicer software to support a biological study that investigates the effect of chronic ethanol exposure on brain morphometry in a longitudinally followed population of male vervets. We first developed a computerized atlas of vervet monkey brain MRI, which was used to encode the typical appearance of the individual brain structures in MRI and their spatial distribution. The atlas was then used as a spatial prior during automatic segmentation to process two longitudinal scans per subject. Our evaluation confirms the consistency and reliability of the automatic segmentation. The comparison of atlas construction strategies reveals that the use of a population-specific atlas leads to improved accuracy of the segmentation for subcortical brain structures. The contribution of this work is twofold. First, we describe an image processing workflow specifically tuned towards the analysis of vervet MRI that consists solely of the open source software tools. Second, we develop a digital atlas of vervet monkey brain MRIs to enable similar studies that rely on the vervet model

Deep Neural Networks for Anatomical Brain Segmentation

We present a novel approach to automatically segment magnetic resonance (MR) images of the human brain into anatomical regions. Our methodology is based on a deep artificial neural network that assigns each voxel in an MR image of the brain to its corresponding anatomical region. The inputs of the network capture information at different scales around the voxel of interest: 3D and orthogonal 2D intensity patches capture the local spatial context while large, compressed 2D orthogonal patches and distances to the regional centroids enforce global spatial consistency. Contrary to commonly used segmentation methods, our technique does not require any non-linear registration of the MR images. To benchmark our model, we used the dataset provided for the MICCAI 2012 challenge on multi-atlas labelling, which consists of 35 manually segmented MR images of the brain. We obtained competitive results (mean dice coefficient 0.725, error rate 0.163) showing the potential of our approach. To our knowledge, our technique is the first to tackle the anatomical segmentation of the whole brain using deep neural networks

Fully-automated μMRI morphometric phenotyping of the Tc1 mouse model of Down Syndrome

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings

Anatomical atlas of the upper part of the human head for electroencephalography and bioimpedance applications

Objective. The objective of this work is to develop a 4D (3D+T) statistical anatomical atlas of the electrical properties of the upper part of the human head for cerebral electrophysiology and bioimpedance applications. Approach. The atlas was constructed based on 3D magnetic resonance images (MRI) of 107 human individuals and comprises the electrical properties of the main internal structures and can be adjusted for specific electrical frequencies. T1w+T2w MRI images were used to segment the main structures of the head while angiography MRI was used to segment the main arteries. The proposed atlas also comprises a time-varying model of arterial brain circulation, based on the solution of the Navier-Stokes equation in the main arteries and their vascular territories. Main results. High-resolution, multi-frequency and time-varying anatomical atlases of resistivity, conductivity and relative permittivity were created and evaluated using a forward problem solver for EIT. The atlas was successfully used to simulate electrical impedance tomography measurements indicating the necessity of signal-to-noise between 100 and 125 dB to identify vascular changes due to the cardiac cycle, corroborating previous studies. The source code of the atlas and solver are freely available to download. Significance. Volume conductor problems in cerebral electrophysiology and bioimpedance do not have analytical solutions for nontrivial geometries and require a 3D model of the head and its electrical properties for solving the associated PDEs numerically. Ideally, the model should be made with patient-specific information. In clinical practice, this is not always the case and an average head model is often used. Also, the electrical properties of the tissues might not be completely known due to natural variability. Anatomical atlases are important tools for in silico studies on cerebral circulation and electrophysiology that require statistically consistent data, e.g. machine learning, sensitivity analyses, and as a benchmark to test inverse problem solvers.Peer reviewe

A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology

The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer

A multimodal computational pipeline for 3D histology of the human brain

ABSTRACT: Ex vivo imaging enables analysis of the human brain at a level of detail that is not possible in vivo with MRI. In particular, histology can be used to study brain tissue at the microscopic level, using a wide array of different stains that highlight different microanatomical features. Complementing MRI with histology has important applications in ex vivo atlas building and in modeling the link between microstructure and macroscopic MR signal. However, histology requires sectioning tissue, hence distorting its 3D structure, particularly in larger human samples. Here, we present an open-source computational pipeline to produce 3D consistent histology reconstructions of the human brain. The pipeline relies on a volumetric MRI scan that serves as undistorted reference, and on an intermediate imaging modality (blockface photography) that bridges the gap between MRI and histology. We present results on 3D histology reconstruction of whole human hemispheres from two donors