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

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.

Pulmonary vascular extraction and distribution of antipyrine with alveolar flooding

1995 ◽  
Vol 269 (5) ◽  
pp. H1811-H1819
Author(s):  
W. O. Cua ◽  
V. Bower ◽  
C. Tice ◽  
F. P. Chinard
Keyword(s):  
Tritiated Water ◽  
Indicator Dilution ◽  
Limiting Factor ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Before And After ◽  
Multiple Indicator ◽  
Dilution Experiments ◽  
Orthogonal Distribution

Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO) were assessed in dog lungs by multiple indicator-dilution experiments in vivo with anesthesia and in isolated perfused preparations before and after alveolar flooding. In controls, outflow patterns of AP and THO were nearly identical. In flooding, AP and THO patterns separated. THO upslopes decreased and mean (t) and modal (tmax) transit times increased as flooding increased; AP initial upslopes remained relatively unchanged but t increased, whereas tmax decreased. Patterns of 22Na+ were unchanged. The results indicate 22Na+ limitation at the endothelium, AP limitation only at the epithelium, and no THO limitation. A mathematical model is based on axial and orthogonal distribution of AP and THO. With alveolar flooding, diffusional distance may be a limiting factor in this distribution.

scholarly journals Transit Time Measurement in Indicator Dilution Curves: Overcoming the Missing Ground Truth and Quantifying the Error

2021 ◽  
Vol 12 ◽  
Author(s):  
Ady Naber ◽  
Michael Reiß ◽  
Werner Nahm
Keyword(s):  
Blood Flow ◽  
Transit Time ◽  
Flow Measurement ◽  
Local Density ◽  
Ground Truth ◽  
Time Measurement ◽  
Indicator Dilution ◽  
In Transit ◽  
Transit Time Measurement ◽  
Dilution Curves

The vascular function of a vessel can be qualitatively and intraoperatively checked by recording the blood dynamics inside the vessel via fluorescence angiography (FA). Although FA is the state of the art in proving the existence of blood flow during interventions such as bypass surgery, it still lacks a quantitative blood flow measurement that could decrease the recurrence rate and postsurgical mortality. Previous approaches show that the measured flow has a significant deviation compared to the gold standard reference (ultrasonic flow meter). In order to systematically address the possible sources of error, we investigated the error in transit time measurement of an indicator. Obtaining in vivo indicator dilution curves with a known ground truth is complex and often not possible. Further, the error in transit time measurement should be quantified and reduced. To tackle both issues, we first computed many diverse indicator dilution curves using an in silico simulation of the indicator's flow. Second, we post-processed these curves to mimic measured signals. Finally, we fitted mathematical models (parabola, gamma variate, local density random walk, and mono-exponential model) to re-continualize the obtained discrete indicator dilution curves and calculate the time delay of two analytical functions. This re-continualization showed an increase in the temporal accuracy up to a sub-sample accuracy. Thereby, the Local Density Random Walk (LDRW) model performed best using the cross-correlation of the first derivative of both indicator curves with a cutting of the data at 40% of the peak intensity. The error in frames depends on the noise level and is for a signal-to-noise ratio (SNR) of 20 dB and a sampling rate of fs = 60 Hz at fs-1·0.25(±0.18), so this error is smaller than the distance between two consecutive samples. The accurate determination of the transit time and the quantification of the error allow the calculation of the error propagation onto the flow measurement. Both can assist surgeons as an intraoperative quality check and thereby reduce the recurrence rate and post-surgical mortality.

Transcapillary exchange of molecular weight markers in the postglomerular circulation: application of a barrier-limited model

1982 ◽  
Vol 242 (5) ◽  
pp. F436-F446
Author(s):  
C. Trainor ◽  
M. Silverman
Keyword(s):  
Molecular Weight ◽  
Excluded Volume ◽  
Excluded Volume Effects ◽  
Multiple Indicator Dilution ◽  
Filtration Barrier ◽  
Transit Times ◽  
Multiple Indicator ◽  
Dilution Experiments ◽  
Volume Effects

The permselectivity of the postglomerular capillary wall was studied by performing pulse-injection multiple indicator-dilution experiments on dog kidneys in vivo, using simultaneous injection of T1824-labeled albumin (plasma reference), creatinine (extracellular reference), and one or two radioactively labeled indicators: raffinose (595 dalton), vitamin B12 (1,357 dalton), or inulin (approximately 5,000 dalton). The urine transit patterns superimposed for all these except albumin, suggesting equal permeability for these molecular weight markers at the level of the glomerular filtration barrier. But the renal vein mean transit times progressively decreased. Therefore, their apparent interstitial volumes of distribution decrease with increasing molecular weight. This could be due to several factors acting singly or in combination: reduced capillary permeability in the postglomerular microcirculation; restricted diffusion in the postglomerular interstitium; or excluded volume effects. Evidence suggested that the effect was due to a combination of permeability and exclusion volume effects. To assess the validity of this assumption, the barrier-limited model was compared with the experimental data. The results were analyzed (both hydropenic and mannitol-diuretic dogs) and best fits calculated using two independent parameters, permeability and excluded volume. For permeability (X10(-4) cm/s, mean +/- SD) the range of values was always greater than or equal to 15 for creatinine and raffinose, and greater than or equal to 12 for B12. The permeability for inulin was 6.9 +/- 1.4. When interstitial volume excluded was expressed as percentage of the volume available to creatine, the excluded volume was negligible for raffinose and B12 but 12 +/- 5% for inulin. During mannitol diuresis the permeability for creatinine and raffinose remained high, but the values tended to decrease for B12. The permeability of inulin decreased to 2.9 +/- 0.09. Mannitol diuresis increased the excluded volume of inulin but did not alter the creatinine, raffinose, or B12 value.

Endothelial extraction of tracer water varies with extravascular water in dog lungs

1987 ◽  
Vol 252 (2) ◽  
pp. H340-H348 ◽  
Author(s):  
F. P. Chinard ◽  
W. O. Cua
Keyword(s):  
Volume Of Distribution ◽  
Indicator Dilution ◽  
Lung Water ◽  
Limited Distribution ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator ◽  
The Time Domain ◽  
Area Product ◽  
Extravascular Volume

In multiple indicator-dilution experiments, transvascular passage of a permeating indicator is conventionally derived from the up-slope separation of the curve of the permeating indicator from that of a vascular reference and is expressed as the extraction (Ec). Extraction may be limited by the barrier (barrier-limited distribution). It may be limited by the volume of distribution accessible to it; in the time domain of an indicator-dilution experiment, the passage to and distribution in the extravascular volume are rapid relative to the velocity of blood in the exchange vessels. We examine here the relations of the extraction of tracer water as tritium oxide (THO) [Ec(THO)] and of the extraction of tracer sodium as 22Na [Ec(22Na)] to extravascular lung water, delta V wev, by adding isotonic fluid to the gas phase of the lungs. The net convective transvascular passage of water is negligible relative to the transendothelial molecular exchange. In 10 experiments in vivo and in 10 experiments in isolated perfused lungs, Ec(THO) increases as delta V wev increases. Ec(22Na) and the permeability-surface area product (PS) for 22Na do not change as delta V wev increases. We conclude that the extraction of THO is determined mainly by the volume accessible to it (flow- or volume-limited distribution) and that the extraction of 22Na is determined mainly by the resistance of the endothelium (barrier-limited distribution). A diffusion limitation in the added alveolar fluid rather than a barrier limitation at the endothelium may moderate Ec(THO).

Determination of glomerular permselectivity to neutral dextrans in the dog

1983 ◽  
Vol 245 (4) ◽  
pp. F485-F495
Author(s):  
C. Whiteside ◽  
M. Silverman
Keyword(s):  
Renal Vein ◽  
Renal Plasma Flow ◽  
Constant Infusion ◽  
Solute Flux ◽  
Left Renal Artery ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Multiple Indicator ◽  
T Values

The multiple-indicator-dilution (MID) technique was used to separate solute flux (Js) across the glomerular and postglomerular capillaries in vivo. Anesthetized mongrel dogs (n = 20) during mannitol diuresis received a pulse of extracellular indicators including 125I-albumin (plasma reference), [14C]inulin (glomerular reference), creatinine (interstitial reference), and a neutral [3H]dextran (specific mol wt between 10,000 and 24,000 dalton) in the left renal artery. Left renal venous and ureteric outflows were rapidly sampled. 3H-labeled dextrans 10,000-15,500 had renal vein mean transit times (t) greater than those of 125I-albumin, indicating postglomerular extraction. 3H-labeled dextrans greater than 15,500 had t values identical to those of 125I-albumin, indicating only unidirectional glomerular extraction. The glomerular fractional dextran extractions relative to simultaneously injected [14C]inulin (ED/Ei) were calculated from urine and renal vein outflow curves and ranged from 0.98 +/- 0.02 to 0.33 +/- 0.12 (SD) for mol wt 10,000 +/- 24,000. ED/Ei values were quantitatively identical to constant-infusion fractional clearances of the same dextrans. Renal plasma flow (RPF) was then deliberately reduced two-to threefold in the same dog. ED/Ei as measured by the MID technique remained unchanged during graded reduction in RPF. In constant-infusion experiments RPF was reduced from 5.78 to 2.77 ml X s-1 X 100 g-1 and GFR from 50.4 to 36.3 ml X min-1, but the fractional neutral dextran clearances remained constant. The predominance of convective solute flux across the dog glomerulus permitted calculation of glomerular reflection coefficients 0.03 +/- 0.06 to 0.85 +/- 0.03 (SD) for neutral 3H-labeled dextrans 10,000-24,000 dalton.

Exchange of multiple indicators across renal-like epithelia: a modeling study of six physiological regimes

1986 ◽  
Vol 251 (6) ◽  
pp. F1073-F1089
Author(s):  
C. J. Lumsden ◽  
M. Silverman
Keyword(s):  
Epithelial Transport ◽  
Transport Processes ◽  
Indicator Dilution ◽  
Mathematical Form ◽  
Multiple Indicators ◽  
Multiple Indicator Dilution ◽  
Tracer Movement ◽  
Wide Range ◽  
Multiple Indicator

Multiple indicator dilution (MID) provides a means of quantifying the unidirectional steady-state fluxes of in vivo tracer movement within organs. In this report a MID model of tracer exchange across renal-like epithelia is developed in mathematical form. Six regimes of epithelial transport function are defined on the basis of the relative sizes of the tracer fluxes. Evidence for the existence of each regime has previously been obtained empirically. These are net secretion, net reabsorption, kinetic sink, antiluminal drive, antiluminal equilibration, and antiluminal trapping. By means of the mathematical model, the indicator dilution properties of the six regimes are compared. The principal similarities and differences among the regimes are documented and related to the physical basis of the transport processes. The findings suggest that over a wide range of physiologically meaningful flux magnitudes the functional regimes can be distinguished via existing empirical methods of MID. The model provides an improved basis for carrying out these distinctions in specific applications.

Estimation of flow Heterogeneity in VIVO from Indicator Dilution Curves

1997 ◽  
Vol 30 (2) ◽  
pp. 35-38
Author(s):  
Chiara Chinello ◽  
Paolo Vicini ◽  
Riccardo C. Bonadonna ◽  
Claudio Cobelli
Keyword(s):  
Indicator Dilution ◽  
Flow Heterogeneity ◽  
Dilution Curves

scholarly journals Capillary endothelial transport of uric acid in guinea pig heart

1992 ◽  
Vol 262 (2) ◽  
pp. H420-H431 ◽  
Author(s):  
K. Kroll ◽  
T. R. Bukowski ◽  
L. M. Schwartz ◽  
D. Knoepfler ◽  
J. B. Bassingthwaighte
Keyword(s):  
Uric Acid ◽  
Endothelial Cell ◽  
Weak Acid ◽  
Cell Permeability ◽  
Guinea Pig Heart ◽  
Multiple Indicator Dilution ◽  
Negative Membrane Potential ◽  
Dilution Curves ◽  
Reference Tracer

Much of the adenosine formed in the heart is degraded by endothelial enzymes to uric acid, which is exported across the coronary capillary endothelial cell membrane before renal excretion. Because previous experiments suggested that cell permeability for uric acid is either very high (similar to water) or very low, multiple indicator-dilution experiments were carried out to distinguish between the two possibilities. An intravascular reference tracer, 131I-labeled albumin, and an extracellular reference tracer, L-[3H]glucose, were injected together with [14C]uric acid as a bolus into the coronary inflow, while fractionating the venous outflow for 90 s. Recovery of injected uric acid averaged 99.0 +/- 2.9% (mean +/- SD, n = 12) that of L-glucose. Peak capillary extraction of L-glucose and uric acid averaged 0.38 +/- 0.032 and 0.42 +/- 0.035 (P less than 0.005) compared with albumin. Except at the peaks, the dilution curves for [14C]uric acid and L-[3H]glucose coincided closely, indicating that little uric acid was transported into cells. The dilution curves were analyzed using an axially distributed, multipathway, four region mathematical model, to estimate membrane permeability-surface area (PS) products. Since the endothelial cell PS for uric acid was low (0.12 +/- 0.09 ml.g-1.min-1), approximately 3% of the PS reported for adenosine, the possibility of flow-limited exchange for uric acid is ruled out. To estimate steady-state endothelial concentrations of uric acid in vivo, equations were developed describing electrochemical potential gradients for dissociated and undissociated forms of a weak acid. Despite endothelial production, intracellular concentrations that are lower than outside are expected because the negative membrane potential and lower cellular pH assist uric acid efflux.

Comparison of labeled propanediol and urea as markers of lung vascular injury

1987 ◽  
Vol 62 (5) ◽  
pp. 1852-1859 ◽  
Author(s):  
T. R. Harris ◽  
R. J. Roselli ◽  
C. R. Maurer ◽  
R. E. Parker ◽  
N. A. Pou
Keyword(s):  
Surface Area ◽  
Indicator Dilution ◽  
Base Line ◽  
Lung Water ◽  
Transit Times ◽  
Permeability Surface ◽  
Permeability Alteration ◽  
Lung Vascular Permeability ◽  
Exchange Surface ◽  
Dilution Curves

The purpose of these studies was a comparison of [14C]urea (U) and 1,3-[14C]propanediol (Pr) as measures of lung vascular permeability-surface area (PS) under base-line conditions and after lung injury caused by alloxan infusion in isolated perfused dog lungs. Indicator mixtures of 125I-albumin, 51Cr-red blood cells, 3HOH, and U or Pr were injected under base-line conditions, after 1.2 g of alloxan, and after an additional 0.8 g of alloxan. Indicator-dilution curves were analyzed from sampled outflow blood to provide PS, the square root of effective extravascular diffusivity multiplied by exchange surface area (D1/2S), and extravascular lung water (EVLW) from the tracer mean transit times (VW). Results show that alloxan increases PS and D1/2S for U, D1/2S for Pr, and VW and EVLW by desiccation. All indicator-dilution parameters correlate significantly with alloxan dose. Interpretation of Pr transport suggests that materials with lipid and hydrophilic pathways might be used in conjunction with U to minimize the effects of surface area changes and increase the sensitivity of these tracers to permeability alteration. In addition Pr may be a useful alternative to U as a marker of vascular damage.

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