An Image-Based Framework for the Analysis of the Murine Microvasculature: From Tissue Clarification to Computational Hemodynamics DOI Creative Commons

Santiago Mañosas,

Aritz Sanz, Cristina Ederra

et al.

Mathematics, Journal Year: 2022, Volume and Issue: 10(23), P. 4593 - 4593

Published: Dec. 4, 2022

The blood–brain barrier is a unique physiological structure acting as filter for every molecule reaching the brain through blood. For this reason, an effective pharmacologic treatment supplied to patient by systemic circulation should first be capable of crossing barrier. Standard cell cultures (or those based on microfluidic devices) and animal models have been used study human Unfortunately, these tools not yet reached state maturity because complexity process aggravated high heterogeneity that easily recapitulated experimentally. In fact, extensive research has performed preclinical trials carried out provided sometimes contradictory results, functionality function still fully understood. study, we combined tissue clarification, advanced microscopy image analysis develop one-dimensional computational model microvasculature hemodynamics inside mouse brain. This can provide information about flow regime, pressure field wall shear stress among other fluid dynamics variables Although it simplified cerebral microvasculature, allows insight into offers several additional possibilities systematically microcirculatory processes.

Language: Английский

Stokes flows in a two-dimensional bifurcation DOI Creative Commons
Yidan Xue, Stephen J. Payne, Sarah L. Waters

et al.

Royal Society Open Science, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 1, 2025

The flow network model is an established approach to approximate pressure–flow relationships in a bifurcating network, and has been widely used many contexts. Existing models typically assume unidirectional exploit Poiseuille’s law, thus neglect the impact of bifurcation geometry finite-sized objects on flow. We determine by computing Stokes flows two-dimensional (2D) using Lightning-AAA Rational algorithm, novel mesh-free algorithm for solving 2D problems utilizing applied complex analysis based rational approximation Goursat functions. compute conductances bifurcations with different channel widths, angles, curved boundary geometries fixed circular objects. quantify difference between computed their Poiseuille law approximations demonstrate importance incorporating detailed into existing models. parametrize as functions dimensionless parameters object machine learning approach, which simple use provides more accurate than law. Finally, details are presented.

Language: Английский

Citations

1

Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction DOI Creative Commons
Florian Goirand, Tanguy Le Borgne, Sylvie Lorthois

et al.

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

Citations

41

Mathematical synthesis of the cortical circulation for the whole mouse brain—part II: Microcirculatory closure DOI
Grant Hartung,

Shoale Badr,

Samuel A. Mihelic

et al.

Microcirculation, Journal Year: 2021, Volume and Issue: 28(5)

Published: Feb. 22, 2021

Recent advancements in multiphoton imaging and vascular reconstruction algorithms have increased the amount of data on cerebrovascular circulation for statistical analysis hemodynamic simulations. Experimental observations offer fundamental insights into capillary network topology but mainly within a narrow field view typically spanning small fraction cortical surface (less than 2%). In contrast, larger-resolution modalities, such as computed tomography (CT) or magnetic resonance (MRI), whole-brain coverage capture only larger blood vessels, overlooking microscopic bed. To integrate acquired at multiple length scales with different neuroimaging modalities to reconcile brain-wide macroscale information microscale data, we developed method synthesizing hemodynamically equivalent networks entire cerebral circulation. This computational approach is intended aid quantification patterns flow metabolism brain. part I, described mathematical framework image-guided generation synthetic covering large arteries from circle Willis through pial leading back venous sinuses. Here II, introduce novel procedures creating microcirculatory closure that mimics realistic We demonstrate our capability synthesize whose morphometrics match empirical graphs three independent state-of-the-art laboratories using image acquisition protocols. also successfully synthesized twelve complete mouse brain hemisphere suitable performing Synthetic arterial microvascular allow predictions. Simulations across all will potentially illuminate organ-wide supply metabolic functions are inaccessible models reconstructed limited spatial coverage.

Language: Английский

Citations

24

Modelling the effects of cerebral microthrombi on tissue oxygenation and cell death DOI
Yidan Xue, Wahbi K. El‐Bouri, Tamás Józsa

et al.

Journal of Biomechanics, Journal Year: 2021, Volume and Issue: 127, P. 110705 - 110705

Published: Aug. 23, 2021

Language: Английский

Citations

18

Quantification of hypoxic regions distant from occlusions in cerebral penetrating arteriole trees DOI Creative Commons
Yidan Xue, Theodosia Georgakopoulou, Anne‐Eva van der Wijk

et al.

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(8), P. e1010166 - e1010166

Published: Aug. 5, 2022

The microvasculature plays a key role in oxygen transport the mammalian brain. Despite close coupling between cerebral vascular geometry and local demand, recent experiments have reported that microvascular occlusions can lead to unexpected distant tissue hypoxia infarction. To better understand spatial correlation hypoxic regions occlusion sites, we used both vivo silico simulations investigate effects of penetrating arteriole trees on hypoxia. In rat model microembolisation, 25 μm microspheres were injected through carotid artery occlude arterioles. representative models human cortical columns, arterioles occluded by simulating same size was simulated using Green’s function method. locations segmented, two novel distance analyses implemented study their correlation. found be present simulations, mainly due hypoperfusion region downstream site. Furthermore, reasonable agreement for sites is shown which indicates good applicability understanding response blood flow microemboli.

Language: Английский

Citations

13

Modeling hypoxia-induced radiation resistance and the impact of radiation sources DOI
Luca Possenti,

Piermario Vitullo,

A. Cicchetti

et al.

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 173, P. 108334 - 108334

Published: March 20, 2024

Language: Английский

Citations

2

Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging – A Symposium Review DOI Creative Commons

Joshua K Marchant,

Natalie Ferris,

Diana Grass

et al.

Neuroinformatics, Journal Year: 2024, Volume and Issue: 22(4), P. 679 - 706

Published: Sept. 23, 2024

Abstract Advances in the spatiotemporal resolution and field-of-view of neuroimaging tools are driving mesoscale studies for translational neuroscience. On October 10, 2023, Center Mesoscale Mapping (CMM) at Massachusetts General Hospital (MGH) Athinoula A. Martinos Biomedical Imaging Institute Technology (MIT) Health Sciences based Neuroimaging Training Program (NTP) hosted a symposium exploring state-of-the-art this rapidly growing area research. “Mesoscale Brain Mapping: Bridging Scales Modalities Neuroimaging” brought together researchers who use broad range imaging techniques to study brain structure function convergence microscopic macroscopic scales. The day-long event centered on areas which CMM has established expertise, including development emerging technologies their application clinical needs basic neuroscience questions. in-person welcomed more than 150 attendees, 57 faculty members, 61 postdoctoral fellows, 35 students, four industry professionals, represented institutions local, regional, international levels. also served training goals both NTP. content, organization, format were planned collaboratively by trainees. Many presented or participated panel discussion, thus contributing dissemination they have developed under auspices findings obtained using those technologies. NTP trainees benefited from included helped organize and/or posters gave “flash” oral presentations. In addition gaining experience presenting work, had opportunities throughout day engage one-on-one discussions with visiting scientists other faculty, potentially opening door future collaborations. presentations provided deep exploration many technological advances enabling progress structural functional imaging. Finally, students worked closely develop report summarizing content putting it broader context current state field share scientific community. We note that references cited here include conference abstracts corresponding poster

Language: Английский

Citations

2

Targeted capillary photothrombosis via multiphoton excitation of Rose Bengal DOI Creative Commons
Patrick Delafontaine-Martel, Cong Zhang, Xuecong Lu

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 43(10), P. 1713 - 1725

Published: Jan. 17, 2023

Microvascular stalling, the process occurring when a capillary temporarily loses perfusion, has gained increasing interest in recent years through its demonstrated presence various neuropathologies. Studying impact of such stalls on surrounding brain tissue is paramount importance to understand their role diseases. Despite efforts trying study stalling events, investigations are hampered by elusiveness and scarcity. In an attempt alleviate these hurdles, we present here novel methodology enabling transient occlusions targeted microvascular segments multiphoton excitation Rose Bengal, established photothrombotic agent. With n = 7 mice C57BL/6 J (5 males 2 females) 95 photothrombosis trials, demonstrate ability triggering reversible blockages illuminating segment during ∼300 s at 1000 nm, using standard Ti:Sapphire femtosecond laser. Furthermore, performed concurrent Optical Coherence Microscopy (OCM) angiography imaging network highlight specificity occlusion duration. Through comparison with control group, conclude that blood flow cessation indeed created agent via temporary, followed recovery less than 24 h. Moreover, Immunohistology points toward mechanism driven adherence neutrophil vascular lumen. This observation seems be promoted inflammation locally activation Bengal.

Language: Английский

Citations

6

Mesh‐free high‐resolution simulation of cerebrocortical oxygen supply with fast Fourier preconditioning DOI Creative Commons

Thomas Ventimiglia,

Andreas A. Linninger

International Journal for Numerical Methods in Biomedical Engineering, Journal Year: 2023, Volume and Issue: 39(8)

Published: May 28, 2023

Abstract Oxygen transfer from blood vessels to cortical brain tissue is representative of a class problems with mixed‐domain character. Large‐scale efficient computation oxygen concentration dependent on the manner in which tubular network coupled mesh. Models explicitly resolve interface between and vasculature contiguous mesh are prohibitively expensive for very dense cerebral microvasculature. We propose mesh‐free technique whereby vascular anatomical (VAN) represented as thin directed graph serves convection oxygen, surrounding extravascular Cartesian grid 3D voxels throughout transported by diffusion. split meshes Schur complement method domain decomposition obtain reduced set system equations at steady state. The use allows corresponding matrix equation be solved approximately fast Fourier transform‐based Poisson solver, an effective preconditioner Krylov subspace iteration. performance this enables steady‐state simulation perfusion anatomically accurate networks down single micron resolution without need supercomputers.

Language: Английский

Citations

6

A dynamic multiscale model of cerebral blood flow and autoregulation in the microvasculature DOI Creative Commons
Ali Daher, Stephen J. Payne

Applied Mathematical Modelling, Journal Year: 2023, Volume and Issue: 123, P. 213 - 240

Published: July 3, 2023

Models of the micro-circulatory blood flow in brain can play a key role understanding variety cerebrovascular diseases that occur microvasculature. These conditions are often linked to structural modifications vessel network, alterations patterns, as well impairment autoregulatory response, all which pathological changes model should be able address if it were have any clinical value. Furthermore, results validated against MRI data, simulations need computationally feasible when used on networks scale an voxel. This requires some form upscaling approach bypasses for explicit architectural representation whole network while maintaining relevant anatomical connections. To this end, we developed hybrid multiscale and autoregulation traces dynamic flow, volume, pressure cortical microvasculature, where discrete topology penetrating vessels is preserved, these then appropriately coupled homogenised capillary bed by spatially distributing support function terminal endings. In contrast other models, here accounts physiological phenomena processes microvessels. We show how adaptive meshing scheme study employed ensure scale-invariant coupling formulation numerically accurate simulations, without compromising computational feasibility model. A statistically voxel generated, parameter values calibrated using Monte Carlo Filtering analysis physiologically informed. The found capture steep gradients been reported at interfaces. response upstream drop, recover cerebral exhibiting characteristic behaviour terms calibre biphasic response. Overall, offers high-quality characterisation microvasculature improved efficiency lays ground whole-brain simulations.

Language: Английский

Citations

6