An anatomic and physiological model of hepatic vascular system

Hepatic function can be characterized by the activity/time curves obtained by imaging the aorta, spleen, and liver. Nonparametric deconvolution of the activity/time curves is clinically useful as a diagnostic tool in determining organ transit times and flow fractions. The use of this technique is limited, however, because of numerical and noise problems in performing deconvolution. Furthermore, the interaction of part of the tracer with the spleen and gastrointestinal tract, before it enters the liver, further obscures physiological information in the deconvolved liver curve. In this paper, a mathematical relationship is derived relating the liver activity/time curve to portal and hepatic behavior. The mathematical relationship is derived by using transit time spectrum/residence time density theory. Based on this theory, it is shown that the deconvolution of liver activity/time curves gives rise to a complex combination of splenic, gastrointestinal, and liver dependencies. An anatomically and physiologically plausible parametric model of the hepatic vascular system has been developed. This model is used in conjunction with experimental data to estimate portal, splenic, and hepatic physiological blood flow parameters for eight normal volunteers. These calculated parameters, which include the portal flow fraction, the splenic blood flow fraction, and blood transit times are shown to adequately correspond to published values. In particular, the model of the hepatic vascular system identifies the portal flow fraction as 0.752 +/- 0.022, the splenic blood flow fraction as 0.180 +/- 0.023, and the liver mean transit time as 13.4 +/- 1.71 s. The model has also been applied to two portal hypertensive patients. The variation in some of the model parameters is beyond normal limits and is consistent with the observed pathology.

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Measurement of relative blood flow, transit-time distributions and transport-model parameters by residue detection when radiotracer recirculates

Journal of Theoretical Biology ◽

10.1016/0022-5193(72)90088-4 ◽

1972 ◽

Vol 37 (3) ◽

pp. 503-529 ◽

Cited By ~ 18

Author(s):

Kenneth B. Larson ◽

Donald L. Snyder

Keyword(s):

Blood Flow ◽

Transit Time ◽

Transport Model ◽

Model Parameters ◽

Residue Detection

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Comparison of Renal Blood Flow and Transit Times Measured by Means of 99mTc-Labelled Erythrocytes and Indocyanine Green in Humans with Normal and Diseased Kidneys

Clinical Science ◽

10.1042/cs0510151 ◽

1976 ◽

Vol 51 (2) ◽

pp. 151-159

Author(s):

F. C. Reubi ◽

C. Vorburger ◽

Gertrud Pfeiffer ◽

S. Golder

Keyword(s):

Blood Flow ◽

Indocyanine Green ◽

Renal Blood Flow ◽

Transit Time ◽

Mean Transit Time ◽

Common Mechanism ◽

Dilution Method ◽

Appearance Time ◽

Vascular Volume ◽

Transit Times

1. In nineteen patients with normal or diseased kidneys, renal blood flow, transit times and vascular volume were determined by means of an indicator-dilution method. Two different indicators, plasma-bound Indocyanine Green (IG) and 99mTc-labelled erythrocytes, were used simultaneously. 2. Comparison of the results indicates that IG slightly overestimates renal blood flow, appearance time, mean transit time and vascular volume, as the erythrocyte/IG ratios averaged 0·972, 0·903, 0·93 and 0·921 respectively. Overestimation of the mean transit time was less apparent when it was prolonged. In patients with reduced renal function, the average blood flow values obtained with the two indicators were in good agreement. 3. It is unlikely that axial streaming of erythrocytes accounts for their shorter mean transit time, because the individual erythrocyte/IG mean transit time ratios were independent of the rate of blood flow and the peripheral packed cell volume. 4. Since the erythrocyte/IG mean transit time ratios correlated significantly with the erythrocyte/IG ratios for appearance time and renal blood flow, the common mechanism leading to a depression of all erythrocyte/IG ratios is presumably extravascular circulation and delayed recovery of a small fraction of IG.

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Distribution of Blood Flow in the Renal Cortex during Saline Loading

Clinical Science ◽

10.1042/cs0380699 ◽

1970 ◽

Vol 38 (6) ◽

pp. 699-712 ◽

Cited By ~ 8

Author(s):

O. Munck ◽

E. de Bono ◽

I. H. Mills

Keyword(s):

Blood Flow ◽

Transit Time ◽

Renal Cortex ◽

Mean Transit Time ◽

Control Period ◽

Isotonic Saline ◽

Saline Infusion ◽

Cortical Blood Flow ◽

Rapid Injection ◽

Transit Times

1. The effect of infusion of isotonic saline on the circulation in the renal cortex in the dog was investigated by an external counting technique involving measurement of the transit times for 85Krypton and 131I-labelled albumin after rapid injection into the renal artery. 2. During saline infusion superficial renal cortical blood flow and overall cortical blood flow rose by 23 and 15%, respectively. There was a 6% rise in the ratio superficial cortical blood flow to overall cortical flow, which however, was not significant. 3. Resistance to flow through cortex decreased. 4. Mean transit time for plasma through cortex decreased from an average of 2·9 sec in the control period to 2·6 and 2·1 sec during saline infusion. 5. Renal cortical blood volume, as estimated from the cortical blood flow and the mean transit time for plasma, was virtually unchanged. 6. These studies indicate that the decrease in resistance to flow during acute isotonic saline infusion is probably caused by a dilatation of the resistance vessels only. No significant redistribution of blood flow in cortex takes place; this, however, does not exclude regional changes in glomerular filtration rate.

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Microscope-Integrated Quantitative Analysis of Intraoperative Indocyanine Green Fluorescence Angiography for Blood Flow Assessment: First Experience in 30 Patients

Operative Neurosurgery ◽

10.1227/neu.0b013e31822f7d7c ◽

2011 ◽

Vol 70 (suppl_1) ◽

pp. ons65-ons74 ◽

Cited By ~ 18

Author(s):

Marcel A. Kamp ◽

Philipp Slotty ◽

Bernd Turowski ◽

Nima Etminan ◽

Hans-Jakob Steiger ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Indocyanine Green ◽

Transit Time ◽

Rise Time ◽

Fluorescence Angiography ◽

Flow Index ◽

Time To Peak ◽

Transit Times ◽

Blood Flow Index

Abstract BACKGROUND: Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. OBJECTIVE: To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. METHODS: We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. RESULTS: For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. CONCLUSION: Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

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Validation of transit-time ultrasound flow probes to directly measure portal blood flow in conscious rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.6.h2701 ◽

1996 ◽

Vol 271 (6) ◽

pp. H2701-H2709 ◽

Cited By ~ 7

Author(s):

M. S. D'Almeida ◽

S. Cailmail ◽

D. Lebrec

Keyword(s):

Blood Flow ◽

Portal Vein ◽

Direct Measurement ◽

Transit Time ◽

Portal Blood Flow ◽

Portal Blood ◽

Radioactive Microspheres ◽

Portal Flow ◽

Conscious Rats ◽

The Relationship

Direct measurement of portal venous blood flow is technically difficult, yet crucial for accurate assessment of liver hemodynamic and metabolic functions. The aim of this investigation was to assess the feasibility of implanting transit-time ultra-sound (TTUS) perivascular flow probes on the portal vein of the rat and to validate this technique as a means of directly measuring portal blood flow in conscious rats. A TTUS flow probe was implanted on the portal veins of 10 rats. One week later, portal flow was measured under basal conditions in these rats by TTUS probes and after pharmacological manipulation of portal flow by intravenous injections of Glypressin or infusions of adenosine while the rats were conscious. Portal flow was simultaneously measured in the same rats using radioactive microspheres. Basal systemic hemodynamics, regional blood flows to splanchnic organs, and portal blood pressure were not significantly modified by the presence of the probe on the portal vein compared with a control group of rats not instrumented with flow probes. Basal portal flows measured by the TTUS and microsphere techniques were not different (20.6 +/- 2.6 and 17.6 +/- 1.3 ml/min). After Glypressin, portal flows measured by the TTUS and microsphere techniques were 12.3 +/- 2.9 and 9.3 +/- 1.9 ml/min and, in response to adenosine, increased to 27.2 +/- 3.4 and 31.3 +/- 4.1 ml/min. There was no significant difference between the TTUS and microsphere flows. Both the relationship between absolute flows and the relationship between changes in flows measured by the two techniques were linear with slopes approaching 1.0. Thus TTUS flow probes can be used to directly measure portal flow from the portal vein in conscious rats. This methodology is as effective as the standard technique of radioactive microspheres. More importantly, the TTUS technique allows for continuous direct measurement of portal flow and eliminates the hazards and sources of error associated with the radioactive microsphere technique.

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Blood flow, capillary transit times, and tissue oxygenation: the centennial of capillary recruitment

Journal of Applied Physiology ◽

10.1152/japplphysiol.00537.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1413-1421

Author(s):

Leif Østergaard

Keyword(s):

Blood Flow ◽

Transit Time ◽

Tissue Oxygenation ◽

Plasma Viscosity ◽

Capillary Endothelium ◽

External Compression ◽

Capillary Recruitment ◽

Transit Times ◽

Vascular Origin ◽

Open Capillaries

The transport of oxygen between blood and tissue is limited by blood’s capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such capillary dysfunction contributes to vascular disease pathology.

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Study of capillary transit time distribution in coherent hemodynamics spectroscopy

Journal of Innovative Optical Health Sciences ◽

10.1142/s179354581550025x ◽

2015 ◽

Vol 08 (02) ◽

pp. 1550025 ◽

Cited By ~ 1

Author(s):

Angelo Sassaroli ◽

Jana Kainerstorfer ◽

Sergio Fantini

Keyword(s):

Blood Flow ◽

Transit Time ◽

Time Distribution ◽

Mean Value ◽

Original Model ◽

Extended Model ◽

Transit Times ◽

Sinusoidal Input ◽

The Mean ◽

Transit Time Distribution

A recently proposed analytical hemodynamic model1 [S. Fantini, NeuroImage85, 202–221 (2014)] is able to predict the changes of oxy, deoxy, and total hemoglobin concentrations (model outputs) given arbitrary changes in blood flow, blood volume, and rate of oxygen consumption (model inputs). One assumption of this model is that the capillary compartment is characterized by a single blood transit time. In this work, we have extended the original model by considering a distribution of capillary transit times and we have compared the outputs of both models (original and extended) for the case of sinusoidal input signals at different frequencies, which realizes the new technique of coherent hemodynamics spectroscopy (CHS). For the calculations with the original model, we have used the mean value of the distribution of capillary transit times considered in the extended model. We have found that, for distributions of capillary transit times having mean values around 1 s and a standard deviation less than about 45% of the mean value, the original and extended models yield the same CHS spectra (i.e., model outputs versus frequency of oscillation) within typical experimental errors. For wider capillary transit time distributions, the two models yield different CHS spectra. By assuming that Poiseuille's law is valid in the capillary compartment, we have related the distribution of capillary transit times to the distributions of capillary lengths and capillary speed of blood flow to calculate the average capillary and venous saturations. We have found that, for standard deviations of the capillary transit time distribution that are less than about 80% of the mean value, the average capillary saturation is always larger than the venous saturation. By contrast, the average capillary saturation may be less than the venous saturation for wider distributions of the capillary transit times.

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Microfluidics of blood in blood vessels stenosis

Proceedings of the Mavlyutov Institute of Mechanics ◽

10.21662/uim2016.2.031 ◽

2016 ◽

Vol 11 (2) ◽

pp. 210-217 ◽

Cited By ~ 1

Author(s):

A.T. Akhmetov ◽

A.A. Valiev ◽

A.A. Rakhimov ◽

S.P. Sametov ◽

R.R. Habibullina

Keyword(s):

Blood Flow ◽

Blood Vessels ◽

Hydraulic Resistance ◽

Microfluidic Device ◽

Human Body ◽

Vascular System ◽

Hydrodynamic Conditions ◽

Microstructure Change ◽

Healthy Part

It is mentioned in the paper that hydrodynamic conditions of a flow in blood vessels with the stenosis are abnormal in relation to the total hemodynamic conditions of blood flow in a vascular system of a human body. A microfluidic device developed with a stepped narrowing for studying of the blood flow at abnormal conditions allowed to reveal blood structure in microchannels simulating the stenosis. Microstructure change is observed during the flow of both native and diluted blood through the narrowing. The study of hemorheological properties allowed us to determine an increasing contribution of the hydraulic resistance of the healthy part of the vessel during the stenosis formation.

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Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-3068 ◽

2020 ◽

Vol 6 (3) ◽

pp. 268-271

Author(s):

Michael Reiß ◽

Ady Naber ◽

Werner Nahm

Keyword(s):

Transit Time ◽

Sampling Rate ◽

Ground Truth ◽

Indicator Dilution ◽

Cross Sectional ◽

In Vivo Measurements ◽

Multiple Indicator Dilution ◽

Transit Times ◽

Dilution Curves

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

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