scholarly journals Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation

2016 ◽  
Vol 10 ◽  
Author(s):  
Louis Gagnon ◽  
Amy F. Smith ◽  
David A. Boas ◽  
Anna Devor ◽  
Timothy W. Secomb ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Transport ◽  
Network Structure ◽  
Cerebral Oxygen ◽  
Microvascular Network ◽  
Microscopic Imaging

In vivo visualization of oxygen transport in microvascular network

1994 ◽  
Vol 267 (5) ◽  
pp. H2068-H2078 ◽  
Author(s):  
T. Itoh ◽  
K. Yaegashi ◽  
T. Kosaka ◽  
T. Kinoshita ◽  
T. Morimoto
Keyword(s):  
Oxygen Transport ◽  
Time Lag ◽  
Epifluorescence Microscopy ◽  
Oxygen Quenching ◽  
Microvascular Network ◽  
Membrane Technique ◽  
Po2 Measurement ◽  
Micropositioning System

Oxygen transport from the blood to the tissues is a diffusive process driven by the gradient of oxygen tension (PO2). We developed an oxygen-quenching fluorescent membrane that allowed visualization of the PO2 distribution near the microvessels as optical patterns on the membrane by epifluorescence microscopy. This membrane was highly gas permeable to allow PO2 measurement and was transparent enough to also permit observation of the microcirculation. In combination with a newly devised gastight chamber and a micropositioning system, this membrane technique made it possible to visualize the PO2 distribution in the rat mesenteric microvascular network under well-defined conditions. Our preliminary findings indicate that the oxygen distribution in the microvascular network is heterogeneous and suggest that there is considerable release of oxygen from the arterioles. The time lag of the system for tracking rapid PO2 changes in vitro was shown to be negligible, indicating that dynamic PO2 changes occurring in vivo can also be assessed. This technique should provide a novel tool for the study of oxygen transport and metabolism under normal and abnormal conditions.

Therapeutic Efficacy of Semisynthetic Supra Perfusion Resuscitation Fluids, EAF Peg Alb and EAF Peg Hb, Are Differentiated By Their Cerebral Effects in Animal Models of Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 773-773
Author(s):  
Craig A Branch ◽  
Min-Hui Cui ◽  
Sangeetha Thangaswamy ◽  
Nicholas Branch ◽  
Seetharama Acharya
Keyword(s):  
Blood Flow ◽  
Sickle Cell Disease ◽  
Oxygen Delivery ◽  
Therapeutic Efficacy ◽  
Systemic Circulation ◽  
Cerebral Oxygen ◽  
Cremaster Muscle ◽  
Cell Disease ◽  
The Brain

Abstract Background: Extension Arm Facilitated (EAF) PEG Alb and EAF PEG Hb are low viscosity semisynthetic hybrid biopolymers which are isoviscous with conventional colloidal plasma expanders but are distinguished from them because they are supra perfusion resuscitation fluids (SPF's). These SPF's have longer half-life, are pseudoplastic and facilitate the production of NO in vivo by increasing shear thinning of RBC's. We recently tested two SPF's, EAF-P5K6 Alb and P3K6 Hb in WT mice, and in two Tg models of Sickle Cell Disease (SCD): the Berkley mouse (BERK), which is a severe anemic model exhibiting a high impairment of systemic blood flow, and in the NY1DD mouse which only exhibits extensive blood flow impairment when challenged with hypoxia followed by reoxygenation. Here we present a comparison of the systemic and cerebral effects of the EAF PEGgylated SPF's. Methods: A single intraperitoneal 10% top-load dose of either drug was given to WT, NY1DD or BERK mice. In NY1DD mice SPF's were administered after hypoxia at the beginning of reoxygenation (8% for 18 hours), while SPF's were given to WT or BERK mice under normoxia conditions. Three hours after the administration of drug, in vivo intra-vital microscopic observation of post-capillary venules in cremaster muscle was performed. In a separate group of WT and BERK animals, we employed MRI to examine the therapeutic efficacy of a single dose of the same SPF's by measuring cerebral blood flow (CBF) and sufficiency of cerebral oxygen delivery (B OLD MRI R esponse to a brief period of H yperO xia, BRHO) serially following treatment. Results: In NY1DD mice, EAF P5K6 Alb significantly attenuated hopoxia reoxygenation induced impairment of cremaster blood flow and associated vaso-occlusion, while EAF P3K6 Hb completely neutralized the experimentally induced sickle crisis. In BERK mice, both SPF's had comparable effects: the chronic state of vaso-occluison as observed in the cremaster muscle was eliminated completely by EAF P3K6-Hb. In MRI experiments in WT mice, both drug candidates resulted in increases in CBF, which resolved over 1 week. The increased CBF was accompanied by decreased BRHO consistent with a pseudo 'luxury perfusion' afforded by the accentuated delivery of oxygen. On the other hand, when BERK mice were treated with EAF P5K6 Alb or EAF P3K6 Hb, CBF trended lower, but with the Alb SPF, BRHO increased, and the Hb SPF, BHRO was unchanged, suggesting that the slightly reduced CBF led to increased O2 deficiency with the PEG-Alb, but not with the PEG-Hb. Conclusion : In WT mice, SPF's increase CBF in the brain where the facility to modify NO production is intact, resulting in over delivery of oxygen as confirmed by reductions in deoxy-Hb levels by BROH imaging, confirming supraperfusionary properties of the SPF's. In SCD animals, both SPF's attenuate muscle vaso-occlusion and restore blood flow. In addition, in experimentally induced sickle crisis (NY1DD), EAF P3K6 Hb maintained O2 level in the plasma and attenuate depolymerization of deoxyHb. In the severely anemic BERK mouse, EAF P5K6-Alb slightly attenuated CBF, likely due to reduced cerebral perfusion pressure (CPP), while O2 extraction increased suggesting that reduced CBF was detrimental to cerebral oxygen delivery. This effect was remediated when EAF P3K6-Hb is administered, which afforded additional oxygen to offset the losses due to reduced CBF. EAF P3K6 Hb led to slightly reduced CBF in NY1DD and BERK mice to levels approaching that obtained after administering EAF P5K6 Alb, but without inducing further oxygen debt. EAF P3K6 Hb appears to be the choice agent as this SPF facilitates increased delivery of O2 to hypoxic tissues thereby neutralizing painful crisis, and protects the brain from further ischemic insults. The influence of SCD on CBF by MRI is opposite to the decrease in blood flow observed in the systemic circulation. The infusion of SFA's increased flow in the systemic circulation, but reduced CBF in a disease dependent fashion. These divergent responses suggest the need for oxygen supplementation when developing SCD therapeutics. In particular, these studies suggest that high oxygen affinity PEG-Hb may have increased the therapeutic efficacy of this SPF by preventing the complete deoxygenation of HbS in the RBC. An antioxidant conjugated to the SFP, such as quercetin, could attenuate the hypoxia reoxygenation induced acute crisis and improve the efficacy of SCD therapeutics. Disclosures No relevant conflicts of interest to declare.

scholarly journals Insights into cerebral haemodynamics and oxygenation utilising in vivo mural cell imaging and mathematical modelling

2017 ◽  
Author(s):  
Paul W. Sweeney ◽  
Simon Walker-Samuel ◽  
Rebecca J. Shipley
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Mathematical Modelling ◽  
Oxygen Transport ◽  
Muscle Activation ◽  
Smooth Muscle Actin ◽  
Blood Velocity ◽  
Mural Cell ◽  
Proxy Measurement

AbstractThe neurovascular mechanisms underpinning the local regulation of cerebral blood flow (CBF) and oxygen transport remain elusive. In this study we have combined novel in vivo imaging of cortical microvascular and mural cell architecture with mathematical modelling of blood flow and oxygen transport, to provide new insights into CBF regulation that would be inaccessible in a conventional experimental context. Our study implicates vasomotion of smooth muscle actin-covered vessels, rather than pericyte-covered capillaries, as the main mechanism for modulating tissue oxygenation. We also resolve seemingly paradoxical observations in the literature around reduced blood velocity in response to arteriolar constrictions and deduce the cause to be propagation of constrictions to upstream penetrating arterioles. We provide support for pericytes acting as signalling conduits for upstream smooth muscle activation, and erythrocyte deformation as a complementary regulatory mechanism. Finally, we caution against the use of blood velocity as a proxy measurement for flow. Our combined imaging-modelling platform complements conventional experimentation allowing cerebrovascular physiology to be probed in unprecedented detail.

scholarly journals Quantitative mapping of cerebral oxygen metabolism using breath-hold calibrated fMRI

2021 ◽  
Author(s):  
Michael Germuska ◽  
Rachael C Stickland ◽  
Antonio Maria Chiarelli ◽  
Hannah L Chandler ◽  
Richard G Wise
Keyword(s):  
Blood Flow ◽  
Oxygen Metabolism ◽  
Oxygen Extraction Fraction ◽  
Arterial Oxygen ◽  
Breath Holding ◽  
Breath Hold ◽  
Neural Function ◽  
Cerebral Oxygen ◽  
Cerebral Oxygen Metabolism

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the rate of cerebral metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. Existing methods of mapping CMRO2, based on respiratory modulation of arterial spin labelling (ASL) and blood oxygen level dependent (BOLD) signals, require lengthy acquisitions and independent modulation of both arterial oxygen and carbon dioxide levels. Here, we present a new simplified method for mapping the rate of cerebral oxygen metabolism that can be performed using a simple breath-holding paradigm. The method incorporates flow-diffusion modelling of oxygen transport and physiological constraints to create a non-linear mapping between the maximum BOLD signal, M, baseline blood flow (CBF0), and CMRO2. A gradient boosted decision tree is used to learn this mapping directly from simulated MRI data. Modelling studies demonstrate that the proposed method is robust to variation in cerebral physiology and metabolism. This new gas-free methodology offers a rapid and pragmatic alternative to existing dual-calibrated methods, removing the need for specialist respiratory equipment and long acquisition times. In-vivo testing of the method, using an 8-minute 45 second protocol of repeated breath-holding, was performed on 15 healthy volunteers, producing quantitative maps of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and CMRO2.

scholarly journals A model for the regulation of cerebral oxygen delivery

1998 ◽  
Vol 85 (2) ◽  
pp. 554-564 ◽  
Author(s):  
Fahmeed Hyder ◽  
Robert G. Shulman ◽  
Douglas L. Rothman
Keyword(s):  
Blood Flow ◽  
Oxygen Delivery ◽  
Current Model ◽  
Oxygen Extraction Fraction ◽  
Physiological Data ◽  
Cerebral Oxygen ◽  
Oxygen Diffusivity ◽  
Wide Range ◽  
Capillary Bed

On the basis of the assumption that oxygen delivery across the endothelium is proportional to capillary plasma[Formula: see text], a model is presented that links cerebral metabolic rate of oxygen utilization ([Formula: see text]) to cerebral blood flow (CBF) through an effective diffusivity for oxygen (D) of the capillary bed. On the basis of in vivo evidence that the oxygen diffusivity properties of the capillary bed may be altered by changes in capillary[Formula: see text], hematocrit, and/or blood volume, the model allows changes in D with changes in CBF. Choice in the model of the appropriate ratio of Ω ≡ (ΔD/D)/(ΔCBF/CBF) determines the dependence of tissue oxygen delivery on perfusion. Buxton and Frank ( J. Cereb. Blood Flow. Metab. 17: 64–72, 1997) recently presented a limiting case of the present model in which Ω = 0. In contrast to the trends predicted by the model of Buxton and Frank, in the current model when Ω > 0, the proportionality between changes in CBF and[Formula: see text] becomes more linear, and similar degrees of proportionality can exist at different basal values of oxygen extraction fraction. The model is able to fit the observed proportionalities between CBF and[Formula: see text] for a large range of physiological data. Although the model does not validate any particular observed proportionality between CBF and[Formula: see text], generally values of ([Formula: see text]/[Formula: see text])/(ΔCBF/CBF) close to unity have been observed across ranges of graded anesthesia in rats and humans and for particular functional activations in humans. The model’s capacity to fit the wide range of data indicates that the oxygen diffusivity properties of the capillary bed, which can be modified in relation to perfusion, play an important role in regulating cerebral oxygen delivery in vivo.

scholarly journals Characterization of Blood Flow in the Mouse Dorsal Spinal Venous System before and after Dorsal Spinal Vein Occlusion

2015 ◽  
Vol 35 (4) ◽  
pp. 667-675 ◽  
Author(s):  
Matthew J Farrar ◽  
Jonathan D Rubin ◽  
Darcy M Diago ◽  
Chris B Schaffer
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Laboratory Mouse ◽  
Microvascular Network ◽  
Vein Occlusion ◽  
Before And After ◽  
Diseased State ◽  
Dorsal Spinal

The availability of transgenic strains has made the laboratory mouse a popular model for the study of healthy and diseased state spinal cord (SC). Essential to identifying physiologic and pathologic events is an understanding of the microvascular network and flow patterns of the SC. Using 2-photon excited fluorescence (2PEF) microscopy we performed in vivo measurements of blood flow in the lower thoracic portion of the mouse dorsal spinal vein (dSV) and in the first upstream branches supplying it, denoted as dorsal ascending venules (dAVs). We found that the dSV had large radiculomedullary veins (RMVs) exiting the SC, and that flow in the dSV between pairs of RMVs was bidirectional. Volumetric flow increased in each direction away from the point of bifurcation. Flow in the upstream dAVs varied with diameter in a manner consistent with a constant distal pressure source. By performing ex vivo 2PEF microscopy of fluorescent-gel perfused tissue, we created a 3-D map of the dorsal spinal vasculature. From these data, we constructed a simple model that predicted changes in the flow of upstream branches after occlusion of the dSV in different locations. Using an atraumatic model of dSV occlusion, we confirmed the predictions of this model in vivo.

Imaging and Measurement of the Separation Surface Between Converging Fluids of Differing Viscosity at a Microscopic Branch

2000 ◽  
Author(s):  
J. P. Peach ◽  
D. L. Hitt
Keyword(s):  
Blood Flow ◽  
Oxygen Transport ◽  
Nonuniform Distribution ◽  
Transport Processes ◽  
Blood Components ◽  
Microvascular Network ◽  
Separation Surface ◽  
Flow Mixing ◽  
Flow Impedance ◽  
Reverse Situation

Abstract The mechanics of branching blood flow is of fundamental importance in understanding the nonuniform distribution of blood components within a microvascular network and, indeed, even within an individual vessel. The nonuniformity resulting from the branch can in turn impact microvascular flow impedance and oxygen transport processes. A construct known as the “separation surface” is often used to describe the flow at converging (venular) and diverging (arteriolar) branches. In the case of two converging flows, the separation surface identifies the portions of the flow in the outlet branch which originated from each of the two feeding branches. The reverse situation holds for a diverging branch. If the converging fluids are immiscible, then the separation surface is a persistent, physical surface within the flow. For converging blood flow, mixing occurs and the separation surface loses its definition with downstream position.

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