Brain Capillary Networks Across Species: A few Simple Organizational Requirements Are Sufficient to Reproduce Both Structure and Function

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: March 26, 2019

Despite the key role of capillaries in neurovascular function, a thorough characterization cerebral capillary network properties is currently lacking. Here, we define range metrics (geometrical, topological, flow, mass transfer, and robustness) for quantification structural differences between brain areas, organs, species, or patient populations and, parallel, digitally generate synthetic networks that replicate organizational features anatomical (isotropy, connectedness, space-filling nature, convexity tissue domains, characteristic size). To reach these objectives, first construct database defined healthy obtained from imaging mouse human brains. Results show are topologically equivalent two species geometrical only differ scaling. Based on results, then devise method which employs constrained Voronoi diagrams to 3D model locally randomized but homogeneous at network-scale. With appropriate choice scaling, have data, demonstrated by comparison metrics. The ability synthetically opens broad applications, ranging systematic computational studies structure-function relationships detailed analysis pathological degeneration, even development templates fabrication biomimetic vascular embedded tissue-engineered constructs.

Language: Английский

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More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction

eLife, Journal Year: 2019, Volume and Issue: 8

Published: July 15, 2019

Our understanding of how capillary blood flow and oxygen distribute across cortical layers to meet the local metabolic demand is incomplete. We addressed this question by using two-photon imaging resting-state microvascular partial pressure (PO2) in whisker barrel cortex awake mice. measurements I-V show that red-blood-cell flux oxygenation heterogeneity, intracapillary resistance delivery, all decrease with depth, reaching a minimum around layer IV, while depth-dependent extraction fraction increased where presumably highest. findings suggest more homogeneous distribution physiological observables relevant transport tissue an important part network adaptation brain metabolism. These results will inform biophysical models layer-specific cerebral delivery consumption improve our diseases affect microcirculation.

Language: Английский

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Imaging faster neural dynamics with fast fMRI: A need for updated models of the hemodynamic response

Progress in Neurobiology, Journal Year: 2021, Volume and Issue: 207, P. 102174 - 102174

Published: Sept. 12, 2021

Language: Английский

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Velocity distributions, dispersion and stretching in three-dimensional porous media

Journal of Fluid Mechanics, Journal Year: 2020, Volume and Issue: 891

Published: March 23, 2020

Language: Английский

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Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Dec. 15, 2021

Abstract Blood microcirculation supplies neurons with oxygen and nutrients, contributes to clearing their neurotoxic waste, through a dense capillary network connected larger tree-like vessels. This complex microvascular architecture results in highly heterogeneous blood flow travel time distributions, whose origin consequences on brain pathophysiology are poorly understood. Here, we analyze highly-resolved intracortical transport simulations establish the physical laws governing macroscopic properties micro-circulation. We show that network-driven anomalous leads emergence of critical regions, whether hypoxic or high concentrations amyloid- β , waste product centrally involved Alzheimer’s Disease. develop Continuous-Time Random Walk theory capturing these dynamics predicting such regions appear much earlier than anticipated by current empirical models under mild hypoperfusion. These findings provide framework for understanding modelling impact dysfunction diseases, including

Language: Английский

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Advancements in modelling human blood brain-barrier on a chip

Biofabrication, Journal Year: 2023, Volume and Issue: 15(2), P. 022003 - 022003

Published: Jan. 23, 2023

Abstract The human Blood Brain Barrier (hBBB) is a complex cellular architecture separating the blood from brain parenchyma. Its integrity and perfect functionality are essential for preventing neurotoxic plasma components pathogens enter brain. Although vital preserving correct activity, low permeability of hBBB represents huge impediment to treat mental neurological disorders or address tumors. Indeed, vast majority potential drug treatments unable reach crossing hBBB. On other hand, can be damaged its increase as result infections in presence neurodegenerative diseases. Current vitro systems vivo animal models used study molecular/drug transport mechanism through have several intrinsic limitations that difficult overcome. In this scenario, Organ-on-Chip (OoC) based on microfluidic technologies considered promising innovative platforms combine handiness an model with complexity living organ, while reducing time costs. review, we focus recent advances OoCs developing models, aim providing reader critical overview main guidelines design manufacture hBBB-on-chip, whose compartments need mimic ‘blood side’ ‘brain barrier, choose cells types both representative convenient, adequately evaluate barrier integrity, stability, functionality.

Language: Английский

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Surmounting photon limits and motion artifacts for biological dynamics imaging via dual-perspective self-supervised learning

PhotoniX, Journal Year: 2024, Volume and Issue: 5(1)

Published: Jan. 5, 2024

Abstract Visualizing rapid biological dynamics like neuronal signaling and microvascular flow is crucial yet challenging due to photon noise motion artifacts. Here we present a deep learning framework for enhancing the spatiotemporal relations of optical microscopy data. Our approach leverages correlations mirrored perspectives from conjugated scan paths, training model suppress blur by restoring degraded spatial features. Quantitative validation on vibrational calcium imaging validates significant gains in correlation (2.2×), signal-to-noise ratio (9–12 dB), structural similarity (6.6×), tolerance compared raw We further apply diverse viv o experiments mouse cerebral hemodynamics zebrafish cardiac dynamics. This enables clear visualization nutrient (30 mm/s) microcirculation systolic diastolic processes heartbeat (2.7 cycle/s), as well cellular vascular structure cortex. Unlike techniques relying temporal correlations, inherent priors avoids motion-induced self-supervised strategy flexibly enhances live under photon-limited motion-prone regimes.

Language: Английский

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A porous circulation model of the human brain for in silico clinical trials in ischaemic stroke

Interface Focus, Journal Year: 2020, Volume and Issue: 11(1), P. 20190127 - 20190127

Published: Dec. 11, 2020

The advancement of ischaemic stroke treatment relies on resource-intensive experiments and clinical trials. In order to improve treatments, such as thrombolysis thrombectomy, we target the development computational tools for in silico trials which can partially replace these animal human with fast simulations. This study proposes a model that will serve part predictive unit within an trial estimating patient outcome function treatment. particular, present work aims at evaluation organ-scale microcirculation brain perfusion prediction. three-compartment porous continuum approach. Firstly, robust method is established compute anisotropic permeability tensors representing arterioles venules. Secondly, vessel encoded arterial spin labelling magnetic resonance imaging clustering are employed create anatomically accurate mapping between large arteries by identifying superficial territories. Thirdly, parameter space problem reduced analysing governing equations experimental data. Fourthly, optimization conducted. Finally, simulations performed tuned obtain maps corresponding open occluded (ischaemic stroke) scenario. map scenario shows promising qualitative agreement computed tomography images caused occlusion. results highlight case occlusion (i) territories essential capture location extent underperfused regions (ii) required give quantitatively realistic estimation change. future, be thoroughly validated against experiments.

Language: Английский

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Retinal blood flow in critical illness and systemic disease: a review

Annals of Intensive Care, Journal Year: 2020, Volume and Issue: 10(1)

Published: Nov. 12, 2020

Assessment and maintenance of end-organ perfusion are key to resuscitation in critical illness, although there limited direct methods or proxy measures assess cerebral perfusion. Novel non-invasive monitoring microcirculation critically ill patients offer the potential for real-time updates improve patient outcomes. Parallel mechanisms autoregulate retinal maintain blood flow meet metabolic demands across a range pressures. Cerebral (CBF) is reduced autoregulation impaired sepsis, but current image CBF do not reproducibly microcirculation. Peripheral microcirculatory may be imaged sublingual conjunctival mucosa sepsis. Retinal can directly by optical coherence tomography angiography (OCTA) during perfusion-deficit states such as other systemic haemodynamic disturbances acute coronary syndrome, inflammatory conditions bowel disease. Monitoring offers enhance care patients, imaging illness biomarker

Language: Английский

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A network-based model of dynamic cerebral autoregulation

Microvascular Research, Journal Year: 2023, Volume and Issue: 147, P. 104503 - 104503

Published: Feb. 9, 2023

Cerebrovascular diseases continue to be one of the leading causes morbidity and mortality in humans. Abnormalities dynamic cerebral autoregulation (dCA) have been implicated many these disease conditions. Accurate models are therefore needed better understand complex pathophysiology behind impaired dCA. We thus present here a simple framework for modelling vessel-driven network model dCA microvasculature, as opposed conventional compartmental approach. Network incorporate actual connectivity anatomy vasculature, thereby allowing us include trace changes calibre morphology individual vessels, investigate spatial specificity heterogeneity various control mechanisms help disentangle their contributions, link parameters physiology. The proposed feedback incorporated at level vessel, pressure flow fields solved within vessel network. In response an upstream drop, is found able recover blood (CBF) while exhibiting characteristic autoregulatory behaviour terms biphasic response. assess feasibility our formulation larger networks by comparing simulation results those obtained using one-dimensional (1D) CBF applied same microvasculature find that very good agreement with 1D solution, significantly reducing computational cost, enabling more detailed adopted future. computationally feasible representative vasculature can increase translatability haemodynamic into clinical environment, which would develop informed treatment guidelines patients cerebrovascular diseases.

Language: Английский

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