scholarly journals Unbiased construction of a temporally consistent morphological atlas of neonatal brain development

2018 ◽  
Author(s):  
Andreas Schuh ◽  
Antonios Makropoulos ◽  
Emma C. Robinson ◽  
Lucilio Cordero-Grande ◽  
Emer Hughes ◽  
...  
Keyword(s):  
Brain Development ◽  
Longitudinal Change ◽  
Abnormal Development ◽  
Cross Sectional ◽  
Brain Images ◽  
Human Connectome Project ◽  
Mean Shape ◽  
Spatio Temporal ◽  
And Function

AbstractPremature birth increases the risk of developing neurocognitive and neurobe-havioural disorders. The mechanisms of altered brain development causing these disorders are yet unknown. Studying the morphology and function of the brain during maturation provides us not only with a better understanding of normal development, but may help us to identify causes of abnormal development and their consequences. A particular difficulty is to distinguish abnormal patterns of neurodevelopment from normal variation. The Developing Human Connectome Project (dHCP) seeks to create a detailed four-dimensional (4D) connectome of early life. This connectome may provide insights into normal as well as abnormal patterns of brain development. As part of this project, more than a thousand healthy fetal and neonatal brains will be scanned in vivo. This requires computational methods which scale well to larger data sets. We propose a novel groupwise method for the construction of a spatio-temporal model of mean morphology from cross-sectional brain scans at different gestational ages. This model scales linearly with the number of images and thus improves upon methods used to build existing public neonatal atlases, which derive correspondence between all pairs of images. By jointly estimating mean shape and longitudinal change, the atlas created with our method overcomes temporal inconsistencies, which are encountered when mean shape and intensity images are constructed separately for each time point. Using this approach, we have constructed a spatio-temporal atlas from 275 healthy neonates between 35 and 44 weeks post-menstrual age (PMA). The resulting atlas qualitatively preserves cortical details significantly better than publicly available atlases. This is moreover confirmed by a number of quantitative measures of the quality of the spatial normalisation and sharpness of the resulting template brain images.

scholarly journals Label-free concurrent 5-modal microscopy (Co5M) resolves unknown spatio-temporal processes in wound healing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Markus Seeger ◽  
Christoph Dehner ◽  
Dominik Jüstel ◽  
Vasilis Ntziachristos
Keyword(s):  
Wound Healing ◽  
Label Free ◽  
Third Harmonic ◽  
Two Photon ◽  
Non Invasive ◽  
Photon Excitation ◽  
Free Mode ◽  
Spatio Temporal ◽  
And Function

AbstractThe non-invasive investigation of multiple biological processes remains a methodological challenge as it requires capturing different contrast mechanisms, usually not available with any single modality. Intravital microscopy has played a key role in dynamically studying biological morphology and function, but it is generally limited to resolving a small number of contrasts, typically generated by the use of transgenic labels, disturbing the biological system. We introduce concurrent 5-modal microscopy (Co5M), illustrating a new concept for label-free in vivo observations by simultaneously capturing optoacoustic, two-photon excitation fluorescence, second and third harmonic generation, and brightfield contrast. We apply Co5M to non-invasively visualize multiple wound healing biomarkers and quantitatively monitor a number of processes and features, including longitudinal changes in wound shape, microvascular and collagen density, vessel size and fractality, and the plasticity of sebaceous glands. Analysis of these parameters offers unique insights into the interplay of wound closure, vasodilation, angiogenesis, skin contracture, and epithelial reformation in space and time, inaccessible by other methods. Co5M challenges the conventional concept of biological observation by yielding multiple simultaneous parameters of pathophysiological processes in a label-free mode.

scholarly journals Automatic Segmentation of the Dorsal Claustrum in Humans Using in vivo High-Resolution MRI

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Shai Berman ◽  
Roey Schurr ◽  
Gal Atlan ◽  
Ami Citri ◽  
Aviv A Mezer
Keyword(s):  
High Resolution ◽  
Automatic Segmentation ◽  
Thin Sheet ◽  
Brain Regions ◽  
Reproducible Research ◽  
Human Connectome Project ◽  
High Resolution Mri ◽  
Magnetic Resonance Imaging Mri ◽  
And Function

Abstract The claustrum is a thin sheet of neurons enclosed by white matter and situated between the insula and the putamen. It is highly interconnected with sensory, frontal, and subcortical regions. The deep location of the claustrum, with its fine structure, has limited the degree to which it could be studied in vivo. Particularly in humans, identifying the claustrum using magnetic resonance imaging (MRI) is extremely challenging, even manually. Therefore, automatic segmentation of the claustrum is an invaluable step toward enabling extensive and reproducible research of the anatomy and function of the human claustrum. In this study, we developed an automatic algorithm for segmenting the human dorsal claustrum in vivo using high-resolution MRI. Using this algorithm, we segmented the dorsal claustrum bilaterally in 1068 subjects of the Human Connectome Project Young Adult dataset, a publicly available high-resolution MRI dataset. We found good agreement between the automatic and manual segmentations performed by 2 observers in 10 subjects. We demonstrate the use of the segmentation in analyzing the covariation of the dorsal claustrum with other brain regions, in terms of macro- and microstructure. We identified several covariance networks associated with the dorsal claustrum. We provide an online repository of 1068 bilateral dorsal claustrum segmentations.

Contrasting effects of simulated microgravity with and without daily −Gx gravitation on structure and function of cerebral and mesenteric small arteries in rats

2009 ◽  
Vol 107 (6) ◽  
pp. 1710-1721 ◽  
Author(s):  
Le-Jian Lin ◽  
Fang Gao ◽  
Yun-Gang Bai ◽  
Jun-Xiang Bao ◽  
Xiao-Feng Huang ◽  
...  
Keyword(s):  
Structural Changes ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Small Arteries ◽  
Functional Studies ◽  
Cell Layers ◽  
And Function

This study was designed to test the hypothesis that a 28-day tail suspension (SUS) could induce hypertrophy and enhanced myogenic and vasoconstrictor reactivity in middle cerebral arteries (MCAs), whereas atrophy and decreased myogenic and vasoconstrictor responses in mesenteric third-order arterioles (MSAs). Also, in addition to the functional enhancement in MCAs, structural changes in both kinds of arteries and functional decrement in MSAs could all be prevented by the intervention of daily 1-h dorsoventral (−Gx) gravitation by restoring to standing posture. To test this hypothesis, vessel diameters to pressure alterations and nonreceptor- and receptor-mediated agonists were determined using a pressure arteriograph with a procedure to measure in vivo length and decrease hysteresis of vessel segments and longitudinal middlemost sections of vessels fixed at maximally dilated state were examined using electron microscopy and histomorphometry. Functional studies showed that 28-day tail-suspended, head-down tilt (SUS) resulted in enhanced and decreased myogenic tone and vasoconstrictor responses, respectively, in MCAs and MSAs. Histomorphometric data revealed that SUS-induced hypertrophic changes in MCAs characterized by increases in thickness (T) and cross-sectional area (CSA) of the media and the number of vascular smooth-muscle-cell layers (NCL), whereas in MSAs, it induced decreases in medial CSA and T and NCL. Daily 1-h −Gx over 28 days can fully prevent these differential structural changes in both kinds of small arteries and the functional decrement in MSAs, but not the augmented myogenic tone and increased vasoreactivity in the MCAs. These findings have revealed special features of small resistance arteries during adaptation to microgravity with and without gravity-based countermeasure.

Axonal Regulation of Central Nervous System Myelination: Structure and Function

2017 ◽  
Vol 24 (1) ◽  
pp. 7-21 ◽  
Author(s):  
Anna Klingseisen ◽  
David A. Lyons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adult Life ◽  
Structure And Function ◽  
Myelinated Axons ◽  
Cross Sectional ◽  
Recent Advances ◽  
Cross Sectional Size ◽  
And Function

Approximately half of the human brain consists of myelinated axons. Central nervous system (CNS) myelin is made by oligodendrocytes and is essential for nervous system formation, health, and function. Once thought simply as a static insulator that facilitated rapid impulse conduction, myelin is now known to be made and remodeled in to adult life. Oligodendrocytes have a remarkable capacity to differentiate by default, but many aspects of their development can be influenced by axons. However, how axons and oligodendrocytes interact and cooperate to regulate myelination in the CNS remains unclear. Here, we review recent advances in our understanding of how such interactions generate the complexity of myelination known to exist in vivo. We highlight intriguing results that indicate that the cross-sectional size of an axon alone may regulate myelination to a surprising degree. We also review new studies, which have highlighted diversity in the myelination of axons of different neuronal subtypes and circuits, and structure-function relationships, which suggest that myelinated axons can be exquisitely fine-tuned to mediate precise conduction needs. We also discuss recent advances in our understanding of how neuronal activity regulates CNS myelination, and aim to provide an integrated overview of how axon-oligodendrocyte interactions sculpt neuronal circuit structure and function.

scholarly journals Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria

2013 ◽  
Vol 210 (8) ◽  
pp. 1635-1646 ◽  
Author(s):  
Alberto Pinzon-Charry ◽  
Tonia Woodberry ◽  
Vivian Kienzle ◽  
Virginia McPhun ◽  
Gabriela Minigo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Acute Infection ◽  
Plasmodium Infection ◽  
Spontaneous Apoptosis ◽  
Cross Sectional ◽  
And Function ◽  
Immature Cells

Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC’s immunotherapeutic potential.

scholarly journals A data-driven approach to optimising the encoding for multi-shell diffusion MRI with application to neonatal imaging

2019 ◽  
Author(s):  
J-Donald Tournier ◽  
Daan Christiaens ◽  
Jana Hutter ◽  
Anthony N. Price ◽  
Lucilio Cordero-Grande ◽  
...  
Keyword(s):  
Information Content ◽  
Diffusion Mri ◽  
Data Driven ◽  
Abnormal Development ◽  
Quality Data ◽  
List Type ◽  
Reconstruction Methods ◽  
Human Connectome Project ◽  
Data Driven Approach

AbstractDiffusion MRI has the potential to provide important information about the connectivity and microstructure of the human brain during normal and abnormal development, non-invasively and in vivo. Recent developments in MRI hardware and reconstruction methods now permit the acquisition of large amounts of data within relatively short scan times. This makes it possible to acquire more informative multi-shell data, with diffusion-sensitisation applied along many directions over multiple b-value shells. Such schemes are characterised by the number of shells acquired, and the specific b-value and number of directions sampled for each shell. However, there is currently no clear consensus as to how to optimise these parameters. In this work, we propose a means of optimising multi-shell acquisition schemes by estimating the information content of the diffusion MRI signal, and optimising the acquisition parameters for sensitivity to the observed effects, in a manner agnostic to any particular diffusion analysis method that might subsequently be applied to the data. This method was used to design the acquisition scheme for the neonatal diffusion MRI sequence used in the developing Human Connectome Project, which aims to acquire high quality data and make it freely available to the research community. The final protocol selected by the algorithm, and currently in use within the dHCP, consists of b = 0, 400, 1000, 2600 s/mm2 with 20, 64, 88 & 128 DW directions per shell respectively.HighlightsA data driven method is presented to design multi-shell diffusion MRI acquisition schemes (b-values and no. directions).This method optimises the multi-shell scheme for maximum sensitivity to the information content in the signal.When applied in neonates, the data suggest that a b=0 + 3 shell strategy is appropriate

scholarly journals Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling

2021 ◽  
Author(s):  
Kanchan Bisht ◽  
Kenneth A Okojie ◽  
Kaushik P Sharma ◽  
Dennis H Lentferink ◽  
Yu-Yo Sun ◽  
...  
Keyword(s):  
Myeloid Cell ◽  
Structure And Function ◽  
Laser Speckle ◽  
Vascular Structure ◽  
Fixed Tissue ◽  
Pannexin 1 ◽  
Spatio Temporal ◽  
Vessel Development ◽  
And Function

Microglia are brain-resident immune cells with a repertoire of functions in the developing, mature and pathological brain. Their wide-ranging roles in physiology include the clearance of cellular debris, elimination of excess synapses, regulation of neuronal activity and contributions to blood vessel development. Despite these known roles for microglia, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, using in vivo acute and longitudinal two-photon imaging in transgenic mice combined with electron microscopy, fixed tissue immunohistochemistry, pharmacological treatments and laser speckle imaging, we document the steady-state interactions between ramified CX3CR1+ myeloid cell somata and capillaries in the brain. We first confirm that these myeloid cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing and contrasting them with parenchymal microglia (PCMs) in their static, dynamic and chronic morphological activities including during microglial depletion and repopulation. Molecularly, we identify microglial-specific purinergic P2RY12 receptors as a receptor regulating CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, to elucidate roles for microglia in vascular structure and function, we eliminated microglia and showed that this triggered capillary dilation, blood flow increase, and impaired vasodilative responses. We find that P2RY12-/- and PANX1-/- mice recapitulate these vascular impairments suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.

scholarly journals The Neurodevelopmental Hypothesis of Huntington’s Disease

2020 ◽  
Vol 9 (3) ◽  
pp. 217-229
Author(s):  
Ellen van der Plas ◽  
Jordan L. Schultz ◽  
Peg C. Nopoulos
Keyword(s):  
At Risk ◽  
Brain Development ◽  
Abnormal Development ◽  
Alternative Theory ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
Brain Structure And Function ◽  
And Function ◽  
Neurodevelopmental Hypothesis ◽  
Abnormal Brain

The current dogma of HD pathoetiology posits it is a degenerative disease affecting primarily the striatum, caused by a gain of function (toxicity) of the mutant mHTT that kills neurons. However, a growing body of evidence supports an alternative theory in which loss of function may also influence the pathology.This theory is predicated on the notion that HTT is known to be a vital gene for brain development. mHTT is expressed throughout life and could conceivably have deleterious effects on brain development. The end event in the disease is, of course, neurodegeneration; however the process by which that occurs may be rooted in the pathophysiology of aberrant development. To date, there have been multiple studies evaluating molecular and cellular mechanisms of abnormal development in HD, as well as studies investigating abnormal brain development in HD animal models. However, direct study of how mHTT could affect neurodevelopment in humans has not been approached until recent years. The current review will focus on the most recent findings of a unique study of children at-risk for HD, the Kids-HD study. This study evaluates brain structure and function in children ages 6–18 years old who are at risk for HD (have a parent or grand-parent with HD).

scholarly journals Multimodal image fusion via deep generative models

2021 ◽  
Author(s):  
Giovanna Maria Dimitri ◽  
Simeon Spasov ◽  
Andrea Duggento ◽  
Luca Passamonti ◽  
Pietro Lio’ ◽  
...  
Keyword(s):  
A Priori ◽  
Generative Models ◽  
Phenotypic Characterization ◽  
Brain Images ◽  
Disease Evolution ◽  
Human Connectome Project ◽  
Neuroimaging Data ◽  
Individual Participant ◽  
Spatio Temporal ◽  
Model Training

AbstractRecently, it has become progressively more evident that classic diagnostic labels are unable to accurately and reliably describe the complexity and variability of several clinical phenotypes. This is particularly true for a broad range of neuropsychiatric illnesses such as depression and anxiety disorders or behavioural phenotypes such as aggression and antisocial personality. Patient heterogeneity can be better described and conceptualized by grouping individuals into novel categories, which are based on empirically-derived sections of intersecting continua that span both across and beyond traditional categorical borders. In this context, neuroimaging data carry a wealth of spatiotemporally resolved information about each patient’s brain. However, they are usually heavily collapsed a priori through procedures which are not learned as part of model training, and consequently not optimized for the downstream prediction task. This is due to the fact that every individual participant usually comes with multiple whole-brain 3D imaging modalities often accompanied by a deep genotypic and phenotypic characterization, hence posing formidable computational challenges.In this paper we design and validate a deep learning architecture based on generative models rooted in a modular approach and separable convolutional blocks (which result in a 20-fold decrease in parameter utilization) in order to a) fuse multiple 3D neuroimaging modalities on a voxel-wise level, b) efficiently convert them into informative latent embeddings through heavy dimensionality reduction, c) maintain excellent generalizability and minimal information loss. As proof of concept, we test our architecture on the well characterized Human Connectome Project database (n=974 healthy subjects), demonstrating that our latent embeddings can be clustered into easily separable subject strata which, in turn, map to extremely different phenotypical information (including organic, neuropsychological, personality variables) which was not included in the embedding creation process.The ability to extract meaningful and separable phenotypic information from brain images alone can aid in creating multi-dimensional biomarkers able to chart spatio-temporal trajectories which may correspond to different pathophysiological mechanisms unidentifiable to traditional data analysis approaches. In turn, this may be of aid in predicting disease evolution as well as drug response, hence supporting mechanistic disease understanding and also empowering clinical trials.

scholarly journals Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

2021 ◽  
Vol 22 (7) ◽  
pp. 3462
Author(s):  
Pauline V. Marck ◽  
Marco T. Pessoa ◽  
Yunhui Xu ◽  
Laura C. Kutz ◽  
Dominic M. Collins ◽  
...  
Keyword(s):  
Protein Content ◽  
Genetically Engineered ◽  
Heart Weight ◽  
Sequencing Analysis ◽  
Cross Sectional ◽  
Hypertrophic Growth ◽  
High Affinity ◽  
Physiological Cardiac Hypertrophy ◽  
And Function

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1r/rα2s/s mouse failed to do so in the α1s/sα2s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.

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