Brain Template Research Articles

Brain Quantitative MRI Metrics in Astronauts as a Unique Professional Group.

As part of its technological sophistication, the International Space Station (ISS) Program operates a robust medical surveillance schedule for its rotating 6-person crew to control the known health risks and to address knowledge gaps related to human health in space flight environment. Recent evidence on visual impairment in a subset of ISS crew has renewed the interest in the effects of long-duration space flight on the central nervous system (CNS). Through retrospective analysis in a sample of 10 healthy astronauts, we demonstrate the utility of multimodal quantitative magnetic resonance imaging (qMRI) with diffusion tensor imaging (DTI)-based customized brain templates to examine the structural attributes of various CNS compartments in this occupational group. The study included 10 healthy astronauts (45-55 years). All subjects had previous space flights with the median duration of 110 days. Multimodal quantitative structural imaging modalities performed and used in analyses. A host of CNS features are presented, which are largely commensurate with the available normative data. Remarkably, some of our findings demonstrate statistically significant positive features suggestive of structural neuroplasticity conceivably associated with the professional activities of astronauts, and compensatory neurogenesis that counterweighs the expected normative volume loss with age. The novelty of this exploratory report is in the demonstration of a qMRI toolset as a potential capability for characterization and surveillance of unique professional groups, and for future prospective examinations of the effects of various long-term exposures on CNS.

Neural mechanisms of mental schema: a triplet of delta, low beta/spindle and ripple oscillations.

Schemas are higher-level knowledge structures that integrate and organise lower-level representations. As internal templates, schemas are formed according to how events are perceived, interpreted and remembered. Although these higher-level units are assumed to play a fundamental role in our daily life from an early age, the neuronal basis and mechanisms of schema formation and use remain largely unknown. It is important to elucidate how the brain constructs and maintains these higher-level units. In order to examine the possible neural underpinnings of schema, we recapitulate previous work and discuss their findings related to schemas as the brain template. We specifically focused on low beta/spindle oscillations, which are assumed to be the key components of schemas, and propose that the brain template is implemented with a triplet of neural oscillations, that is delta, low beta/spindle and ripple oscillations.

Multivariate Classification of Major Depressive Disorder Using the Effective Connectivity and Functional Connectivity.

Major depressive disorder (MDD) is a mental disorder characterized by at least 2 weeks of low mood, which is present across most situations. Diagnosis of MDD using rest-state functional magnetic resonance imaging (fMRI) data faces many challenges due to the high dimensionality, small samples, noisy and individual variability. To our best knowledge, no studies aim at classification with effective connectivity and functional connectivity measures between MDD patients and healthy controls. In this study, we performed a data-driving classification analysis using the whole brain connectivity measures which included the functional connectivity from two brain templates and effective connectivity measures created by the default mode network (DMN), dorsal attention network (DAN), frontal-parietal network (FPN), and silence network (SN). Effective connectivity measures were extracted using spectral Dynamic Causal Modeling (spDCM) and transformed into a vectorial feature space. Linear Support Vector Machine (linear SVM), non-linear SVM, k-Nearest Neighbor (KNN), and Logistic Regression (LR) were used as the classifiers to identify the differences between MDD patients and healthy controls. Our results showed that the highest accuracy achieved 91.67% (p < 0.0001) when using 19 effective connections and 89.36% when using 6,650 functional connections. The functional connections with high discriminative power were mainly located within or across the whole brain resting-state networks while the discriminative effective connections located in several specific regions, such as posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC), dorsal cingulate cortex (dACC), and inferior parietal lobes (IPL). To further compare the discriminative power of functional connections and effective connections, a classification analysis only using the functional connections from those four networks was conducted and the highest accuracy achieved 78.33% (p < 0.0001). Our study demonstrated that the effective connectivity measures might play a more important role than functional connectivity in exploring the alterations between patients and health controls and afford a better mechanistic interpretability. Moreover, our results showed a diagnostic potential of the effective connectivity for the diagnosis of MDD patients with high accuracies allowing for earlier prevention or intervention.

A stereotaxic breed-averaged, symmetric T2w canine brain atlas including detailed morphological and volumetrical data sets

Stereotaxic systems and automatic tissue segmentation routines enable neuronavigation as well as reproducible processing of neuroimage datasets. Such systems have been developed for humans, non-human-primates, sheep, and rodents, but not for dogs. Although dogs share important neurofunctional and -anatomical features with humans, and in spite of their importance in translational neuroscience, little is known about the variability of the canine brain morphology and, possibly related, function. Moreover, we lack templates, tissue probability maps (TPM), and stereotaxic brain labels for implementation in standard software utilities such as Statistical Parametric Mapping (SPM). Hence, objective and reproducible, image-based investigations are currently impeded in dogs. We have created a detailed stereotaxic reference frame for dogs including TPM and tissue labels, enabling inter-individual and cross-study neuroimage analysis.T2w datasets were acquired from 16 neurologically inconspicuous dogs of different breeds by 3T MRI. The datasets were averaged after initial preprocessing using linear and nonlinear registration algorithms as implemented in SPM8. TPM for gray (GM) and white matter (WM) as well as cerebrospinal fluid (CSF) were created. Different cortical, subcortical, medullary, and CSF regions were manually labeled to create a spatial binary atlas being aligned with the template. A proof-of-concept for automatic determination of morphological and volumetrical characteristics was performed using additional canine datasets (n = 64) including a subgroup of laboratory beagles (n = 24).Overall, 21 brain regions were labeled using the segmented tissue classes of the brain template. The proof-of-concept trial revealed excellent suitability of the created tools for image processing and subsequent analysis. There was high intra-breed variability in frontal lobe and hippocampus volumes, and noticeable inter-breed corpus callosum volume variation.The T2w brain template provides important, breed-averaged canine brain anatomy features in a spatial standard coordinate system. TPM allows automatic tissue segmentation using SPM and enables unbiased automatic image processing or morphological characterization in different canine breeds. The reported volumetric and morphometric results may serve as a starting point for further research aimed at in vivo analysis of canine brain anatomy and function.

Topologically Constrained Template Estimation via Morse--Smale Complexes Controls Its Statistical Consistency

In most neuroimaging studies, one builds a brain template that serves as a reference for normalizing the measurements of each individual subject into a common space. Such a template should be repre...

INCF Program on Digital Brain Atlasing workshop: Towards a multi-modal human brain atlas

This workshop was organized by INCF in Seattle, Washington, United States, 14 - 15 June 2013. The workshop aim was to assess the current state of the human brain mapping field and atlas generation to determine the requirements and challenges to the development of a multi-modal human brain atlas. INCF convened a 2-day workshop with scientists representing different aspects in this field to discuss the challenges and potential of a multi-modal human brain atlas model. Specifically, scientists from the brain mapping subfields of: High field MR imaging, Microstructure, Macroscopical and high throughput MR data, Functional brain atlases, and Time domain presented an overview of the atlasing needs of their respective brain mapping fields and discussed the following questions: How do you envision a comprehensive multimodal model of the human brain? Which data should be included in the multimodal model of the human brain? Which data standards are necessary? How do we handle ontology? Which reference spaces should be supported? The participants agreed that a single (even multi-modal) human brain model would not be an appropriate choice; instead, they believed that a truly multi-modal human brain model would live in a collection of a few interoperable brain templates bridged by established pipelines. The participants identified 4 key challenges that must be overcome to achieve the multi-modal model they envisioned. The challenges identified were (i) correspondence between reference spaces, templates, and atlases, (ii) heterogeneity of features, (iii) integration of information into labels and maps, and (iv) the decision between labeling regions or mapping features. To resolve these challenges and move towards the envisioned multimodal model, the participants believed that (i) pipelines would have to be created to go between the various templates, (ii) a framework that integrates heterogeneous information at different levels of abstraction would have to be established, and (iii) distinction would have to be made between labels and descriptions. In addition to scientists from the different brain mapping fields, scientists from the neuroinformatics community were also invited and presented informatics-based approaches to brain mapping. The overall objective of the 2-day workshop was to identify the key challenges impeding this vision of a multi-modal human brain atlas and discussed what developments are needed to put it into reality

Four-dimensional map of the human early visual system

ObjectiveWe generated a large-scale, four-dimensional map of neuronal modulations elicited by full-field flash stimulation. MethodsWe analyzed electrocorticography (ECoG) recordings from 63 patients with focal epilepsy, and delineated the spatial-temporal dynamics of visually-elicited high-gamma70-110 Hz amplitudes on a standard brain template. We then clarified the neuronal events underlying visual evoked potential (VEP) components, by correlating with high-gamma amplitude measures. ResultsThe medial-occipital cortex initially revealed rapid neural activation followed by prolonged suppression, reflected by augmentation of high-gamma activity lasting up to 100 ms followed by attenuation lasting up to 1000 ms, respectively. With a number of covariate factors incorporated into a prediction model, the eccentricity representation independently predicted the magnitude of post-activation suppression, which was more intense in regions representing more parafoveal visual fields compared to those of more peripheral fields. The initial negative component on VEP was sharply contoured and co-occurred with early high-gamma augmentation, whose offset then co-occurred with a large positive VEP peak. A delayed negative VEP peak was blunt and co-occurred with prolonged high-gamma attenuation. ConclusionsEccentricity-dependent gradient in neural suppression in the medial-occipital region may explain the functional difference between peripheral and parafoveal/central vision. Early negative and positive VEP components may reflect neural activation, whereas a delayed negative VEP peak reflecting neural suppression. SignificanceOur observation provides the mechanistic rationale for transient scotoma or mild flash-blindness, characterized by physiological afterimage preferentially formed in central vision following intense but non-injurious light exposure.

PAM50: Unbiased multimodal template of the brainstem and spinal cord aligned with the ICBM152 space

Template-based analysis of multi-parametric MRI data of the spinal cord sets the foundation for standardization and reproducibility, thereby helping the discovery of new biomarkers of spinal-related diseases. While MRI templates of the spinal cord have been recently introduced, none of them cover the entire spinal cord. In this study, we introduced an unbiased multimodal MRI template of the spinal cord and the brainstem, called PAM50, which is anatomically compatible with the ICBM152 brain template and uses the same coordinate system. The PAM50 template is based on 50 healthy subjects, covers the full spinal cord (C1 to L2 vertebral levels) and the brainstem, is available for T1-, T2-and T2*-weighted MRI contrasts and includes a probabilistic atlas of the gray matter and white matter tracts. Template creation accuracy was assessed by computing the mean and maximum distance error between each individual spinal cord centerline and the PAM50 centerline, after registration to the template. Results showed high accuracy for both T1- (mean = 0.37 ± 0.06 mm; max = 1.39 ± 0.58 mm) and T2-weighted (mean = 0.11 ± 0.03 mm; max = 0.71 ± 0.27 mm) contrasts. Additionally, the preservation of the spinal cord topology during the template creation process was verified by comparing the cross-sectional area (CSA) profile, averaged over all subjects, and the CSA profile of the PAM50 template. The fusion of the PAM50 and ICBM152 templates will facilitate group and multi-center studies of combined brain and spinal cord MRI, and enable the use of existing atlases of the brainstem compatible with the ICBM space.

Robust Fusion of Diffusion MRI Data for Template Construction

Construction of brain templates is generally carried out using a two-step procedure involving registering a population of images to a common space and then fusing the aligned images to form a template. In practice, image registration is not perfect and simple averaging of the images will blur structures and cause artifacts. In diffusion MRI, this is further complicated by intra-voxel inter-subject differences in fiber orientation, fiber configuration, anisotropy, and diffusivity. In this paper, we propose a method to improve the construction of diffusion MRI templates in light of inter-subject differences. Our method involves a novel q-space (i.e., wavevector space) patch matching mechanism that is incorporated in a mean shift algorithm to seek the most probable signal at each point in q-space. Our method relies on the fact that the mean shift algorithm is a mode seeking algorithm that converges to the mode of a distribution and is hence robust to outliers. Our method is therefore in effect seeking the most probable signal profile at each voxel given a distribution of signal profiles. Experimental results show that our method yields diffusion MRI templates with cleaner fiber orientations and less artifacts caused by inter-subject differences in fiber orientation.

Disease-specific brain template for quantification of brain dopamine transporter in Parkinson’s disease

Background: Dopamine transporter (DAT) imaging is an important noninvasive method for detecting neurodegeneration in Parkinson's disease (PD). For automatic quantification of striatal DAT activity, a brain template from healthy control (HC) is often used for spatial normalization. However, the automated warping algorithms may produce inappropriate solution when normalizing brains with striatal lesions.

Hippocampus-dependent spatial learning is associated with higher global cognition among healthy older adults

Cognitive deficits in normal aging have been associated with atrophy of the hippocampus. As such, methods to detect early dysfunction of the hippocampus have become valuable, if not indispensable, to early intervention. The hippocampus is critical for spatial memory and is among the first structures to atrophy with aging. Despite the presence of navigation deficits in aging, few studies have looked at the association between wayfinding ability, navigation strategies, general cognitive function, and hippocampal volume. In the current study we investigated whether better general cognitive function is associated with the use of hippocampal-dependent spatial strategies, better spatial memory, and increased hippocampal volume. We also investigated, within older adults, the effects of aging on spatial memory. Healthy older adults (N = 107) were tested on a virtual wayfinding task and a dual-solution navigation task that can be solved using either a hippocampal-dependent spatial strategy or a caudate nucleus-dependent response strategy. Participants were also administered the Montreal Cognitive Assessment (MoCA), a test that measures general cognition and is sensitive to dementia. A structural MRI was administered to a sub-set of participants (n = 49) and hippocampal volume was calculated using a Multiple Automatically Generated Templates (MAGeT) Brain algorithm. We found that age was negatively associated with wayfinding ability and hippocampal volume. On the wayfinding task, participants with higher MoCA scores found more target locations and travelled shorter distances. We also found a significant association between higher MoCA scores and spatial strategy use. MoCA scores, spatial memory ability, and spatial strategy use all positively correlated with a larger hippocampal volume. These results confirm that with age there is a decrease in spatial memory, which is consistent with decreased volume in the hippocampus with aging. Furthermore, better general cognitive function is associated with better wayfinding ability and increased use of hippocampal-dependent spatial strategies.

Stereotaxic 18F-FDG PET and MRI templates with three-dimensional digital atlas for statistical parametric mapping analysis of tree shrew brain

BackgroundTree shrews are proposed as an alternative animal model to nonhuman primates due to their close affinity to primates. Neuroimaging techniques are widely used to study brain functions and structures of humans and animals. However, tree shrews are rarely applied in neuroimaging field partly due to the lack of available species specific analysis methods. New methodIn this study, 10 PET/CT and 10 MRI images of tree shrew brain were used to construct PET and MRI templates; based on histological atlas we reconstructed a three-dimensional digital atlas with 628 structures delineated; then the digital atlas and templates were aligned into a stereotaxic space. Finally, we integrated the digital atlas and templates into a toolbox for tree shrew brain spatial normalization, statistical analysis and results localization. ResultsWe validated the feasibility of the toolbox by simulated data with lesions in laterodorsal thalamic nucleus (LD). The lesion volumes of simulated PET and MRI images were (12.97±3.91)mm3 and (7.04±0.84)mm3. Statistical results at p<0.005 showed the lesion volumes of PET and MRI were 13.18mm3 and 8.06mm3 in LD. Comparison with existing method(s)To our knowledge, we report the first PET template and digital atlas of tree shrew brain. Compared to the existing MRI templates, our MRI template was aligned into stereotaxic space. And the toolbox is the first software dedicated for tree shrew brain analysis. ConclusionsThe templates and digital atlas of tree shrew brain, as well as the toolbox, facilitate the use of tree shrews in neuroimaging field.

Populational brain models of diffusion tensor imaging for statistical analysis: a complementary information in common space

Abstract Introduction: The search for human brain templates has been progressing in the past decades and in order to understand disease patterns a need for a standard diffusion tensor imaging (DTI) dataset was raised. For this purposes, some DTI templates were developed which assist group analysis studies. In this study, complementary information to the most commonly used DTI template is proposed in order to offer a patient-specific statistical analysis on diffusion-weighted data. Methods 131 normal subjects were used to reconstruct a population-averaged template. After image pre processing, reconstruction and diagonalization, the eigenvalues and eigenvectors were used to reconstruct the quantitative DTI maps, namely fractional anisotropy (FA), mean diffusivity (MD), relative anisotropy (RA), and radial diffusivity (RD). The mean absolute error (MAE) was calculated using a voxel-wise procedure, which informs the global error regarding the mean intensity value for each quantitative map. Results the MAE values presented a low MAE estimate (max(MAE) = 0.112), showing a reasonable error measure between our DTI-USP-131 template and the classical DTI-JHU-81 approach, which also shows a statistical equivalence (p<0.05) with the classical DTI template. Hence, the complementary standard deviation (SD) maps for each quantitative DTI map can be added to the classical DTI-JHU-81 template. Conclusion In this study, variability DTI maps (SD maps) were reconstructed providing the possibility of a voxel-wise statistical analysis in patient-specific approach. Finally, the brain template (DTI-USP-131) described here was made available for research purposes on the web site (http://dx.doi.org/10.17632/br7bhs4h7m.1), being valuable to research and clinical applications.

Using Large-Scale Statistical Chinese Brain Template (Chinese2020) in Popular Neuroimage Analysis Toolkits.

Given that the morphology of Chinese brains statistically differs from that of Caucasian, there is an urgent need to develop a Chinese brain template for neuroimaging studies in Chinese populations. Based on a multi-center dataset, we developed a statistical Chinese brain template, named as Chinese2020 (Liang et al., 2015). This new Chinese brain atlas has been validated in brain normalization and segmentation for anatomical Magnetic Resonance Imaging (MRI) studies, and is publicly available at http://www.chinese-brain-atlases.org/. In our previous study, we have demonstrated this Chinese atlas showed higher accuracy in segmentation and relatively smaller shape deformations during registration. Because the spatial normalization of functional images is mainly based on the segmentation and normalization of anatomical image, the population-specific brain atlas should also be more appropriate for functional studies involving Chinese populations. The aim of this technology report is to validate the performance of Chinsese2020 template in functional neuroimaging studies, and demonstrated that for Chinese population studies, the use of the Chinese2010 template produces more valid results. The steps of how to use the Chinese2020 template in SPM software were given in details in this technology report, and based on an example of finger tapping fMRI study, this technology report demonstrated the Chinese2020 template could improve the performance of the neuroimaging analysis of Chinese populations.

Rat brain digital stereotaxic white matter atlas with fine tract delineation in Paxinos space and its automated applications in DTI data analysis

PurposeTo automatically analyze diffusion tensor images of the rat brain via both voxel-based and ROI-based approaches, we constructed a new white matter atlas of the rat brain with fine tracts delineation in the Paxinos and Watson space. Materials and methodsUnlike in previous studies, we constructed a digital atlas image from the latest edition of the Paxinos and Watson. This atlas contains 111 carefully delineated white matter fibers. A white matter network of rat brain based on anatomy was constructed by locating the intersection of all these tracts and recording the nuclei on the pathway of each white matter tract. Moreover, a compatible rat brain template from DTI images was created and standardized into the atlas space. To evaluate the automated application of the atlas in DTI data analysis, a group of rats with right-side middle cerebral artery occlusion (MCAO) and those without were enrolled in this study. ResultsThe voxel-based analysis result shows that the brain region showing significant declines in signal in the MCAO rats was consistent with the occlusion position. ConclusionWe constructed a stereotaxic white matter atlas of the rat brain with fine tract delineation and a compatible template for the data analysis of DTI images of the rat brain.

Catlas: An magnetic resonance imaging-based three-dimensional cortical atlas and tissue probability maps for the domestic cat (Felis catus).

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter-regional connectivity. Here, we introduce a three-dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1-weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes.

Chinese Color Nest Project: Growing up in China

To face the challenges of keeping healthy in increasing population sizes of both ageing and developing people in China, a fundamental request from the public health is the development of lifespan normative trajectories of brain and behavior. This paper introduces the Chinese Color Nest Project (CCNP 2013–2022), a large-scale ten-year program of modeling brain and behavioral trajectories for human lifespan (6–85 years old). We plan to gradually collect the behavioral and brain imaging data at ages across the lifespan on nationwide and depict the normal trajectory of Chinese brain development across the lifespan, based on the accelerated longitudinal design in the coming next 10 years starting at 2013. Various psychiatric disorders have been demonstrated highly relevant to abnormal events during the neurodevelopment regarding their onset ages of first episodes. Therefore, delineation of normative growth curves of brain and cognition in typically developing children is extremely useful for monitoring, early detecting and intervention of various neurodevelopmental disorders. In this paper, we detailed the developing part of CCNP, devCCNP. It tracked 192 healthy children and adolescents (6–18 years old) in Beibei district of Chongqing for the first 5 years of the full CCNP cohort (2013–2017). To demonstrate the feasibility of implementing the long-term follow-up of CCNP, we here comprehensively document devCCNP in terms of its experimental design, sample strategies, data acquisition and storage as well as some preliminary results and data sharing roadmap for future. Specifically, we first describe the accelerated longitudinal sampling design as well as its exact ratioof sample dropping off during the data collection. Second, we present several initial findings such as canonical growth curves of cortical surface areas of a set of well-established large-scale functional networks of the human brain. Finally, together with records generated by many psychological and behavioral tests, we will provide an individual growing-up report for each family participating the program, initiating the potential guidance on the individual academic and social development. The resources introduced in the current work can provide first-hand data for a series of coming Chinese brain development studies, such as Chinese Standard MRI Brain Templates, Normative Growth Curves of Chinese Brain and Cognition as well as Mapping of Language Areas in Chinese Developing Brain. These would not only offer normative references of the atypical brain and cognition development for Chinese population but also serve as a strong force on accelerating the pace of integrating Chinese brain development into the national brain program or Chinese Brain Project.

34 A lesion map of secondary bipolar disorder

Objective Bipolar Disorder (BPD) is a severe mood disorder, affecting 1.5%–4.4% of the population, and manifesting as an episodic, recurrent disturbance of mood, sleep, and behaviour. Secondary BPD (SBPD) develops following a brain insult, and is traditionally associated with right frontal lobe lesions. Yet, evidence supporting this association is mostly anecdotal. Here, we use two methodologies to study the neuroanatomy of SBPD: a systematic review of SBPD cases published in the literature, and reconstitution of brain lesions from a cohort of patients with SBPD in a single 3D template brain. Method Systematic search of pubmed and WebOfScience for SBPD. For the lesion-map, data were collected from 16 consecutive patients (6 women, 10 men, mean age 60,75±14,27 years) with SBPD developing after an MRI-documented right-sided brain-lesion. For each scan we selected the sequence (T1, T2, or FLAIR) providing the best lesion discrimination. Lesions were manually segmented using MITK software.1 After segmentation, each scan was co-registered onto a template reference brain2 using 3DSlicer software.3 Co-registration applies a transformation vector along the three axes of the source image, such that its voxels match the reference brain voxels to the highest possible degree. The resulting transformation vector was then applied to the image of each segmented lesion, and all the co-registered lesions were overlapped on the template brain scan (Automated anatomical labelling atlas or John Hopkins University white matter tractography Atlas for gray- and white-matter analysis, respectively). Results 1476 articles were found in literature review, with 207 eligible cases, including 193 with focal brain lesions, mostly right-sided (84.5%) and more rarely left-sided (34.7%). Lesions were overrepresented in the frontal and temporal lobes bilaterally. In the 3D lesion-map, lesions were spread over the right hemisphere, with highest overlap in a medial area of the superior frontal gyrus (6 patients). Grey-matter quantitative mapping showed that the right superior frontal gyrus right anterior cingulate and supramarginal gyrus and right insula were lesioned in the highest number of patients (respectively 8, 7 and 6 patients). White-matter analysis highlighted the right superior longitudinal fasciculus and superior corona radiata (6 patients each), anterior corona radiata and body of corpus callosum (5 patients each). Conclusion Our systematic review confirmed that right-sided frontotemporal lesions predominate in SBPD. In our cohort lesions converged on areas of the right executive control and anterior salience networks. Both have been implicated in the neurophysiology of primary BPD.4,5

Whole mouse brain imaging using optical coherence tomography: reconstruction, normalization, segmentation, and comparison with diffusion MRI.

An automated massive histology setup combined with an optical coherence tomography (OCT) microscope was used to image a total of [Formula: see text] whole mouse brains. Each acquisition generated a dataset of thousands of OCT volumetric tiles at a sampling resolution of [Formula: see text]. This paper describes techniques for reconstruction and segmentation of the sliced brains. In addition to the measured OCT optical reflectivity, a single scattering photon model was used to compute the attenuation coefficients within each tissue slice. Average mouse brain templates were generated for both the OCT reflectivity and attenuation contrasts and were used with an [Formula: see text]-tissue segmentation algorithm. To better understand the brain tissue OCT contrast origin, one of the mouse brains was acquired using dMRI and coregistered to its corresponding assembled brain. Our results indicate that the optical reflectivity in a fiber bundle varies with its orientation, its fiber density, and the number of fiber orientations it contains. The OCT mouse brain template generation and coregistration to dMRI data demonstrate the potential of this massive histology technique to pursue cross-sectional, multimodal, and multisubject investigations of small animal brains.

Arterial branching and basal ganglia lacunes: A study in pure small vessel disease.

Lacunes are defined morphologically by size and location, but radiological characteristics alone may be unable to distinguish small vessel disease aetiology from alternative mechanisms. We investigated the branching order of arterial vessels associated with basal ganglia lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in order to improve the understanding of their pathogenesis in pure cerebral small vessel disease. Adults with a confirmed diagnosis of CADASIL were included. A pilot study was conducted in a Scottish CADASIL cohort. The Paris-Munich CADASIL cohort was used for independent validation. Lacunes identified on T1-weighted magnetic resonance imaging scans were registered to a standard brain template. A microangiographic template of the basal ganglia vasculature was automatically overlaid onto coronal slices, and raters estimated the vessel branching order related to each lacune. Of 179 lacunes, 150 (84%) were associated with third-order vessels. In 14 incident lacunes, 11 (79%) were associated with third-order vessels. In the pilot study, lacune volume was significantly lower in lacunes associated with third-order vessels (0.04 ml ± 0.04 ml) compared to second-order vessels (0.48 ± 0.16 ml; p < 0.001). In this study of CADASIL patients, most lacunes were small and associated with third-order vessel disease. This suggests that these are the vessels primarily affected in cerebral small vessel disease. Microangiographic template techniques could be used to further investigate in a general stroke population whether finding large lacunes originating from higher order vessels indicates an alternative cause of stroke. Lacunes in pure small vessel disease are associated with the smallest vessels in the basal ganglia.