Clearance and Non-Invasive Determination of the Hepatic Extraction of Indocyanine Green in Baboons and Man

1983 ◽  
Vol 64 (2) ◽  
pp. 207-212 ◽  
Author(s):  
S. L. Grainger ◽  
P. W. N. Keeling ◽  
I. M. H. Brown ◽  
J. H. Marigold ◽  
R. P. H. Thompson

1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and noninvasively after a single intravenous injection of ICG.

1989 ◽  
Vol 76 (5) ◽  
pp. 503-508 ◽  
Author(s):  
E. Burns ◽  
C. E. Ball ◽  
J. P. Christie ◽  
G. D. Broadhead ◽  
G. T. Tucker ◽  
...  

1. In order to estimate liver blood flow in the rat, the extraction ratio of Indocyanine Green was determined using a two-compartment model fitted to the plasma concentration time data after a single intravenous bolus dose and compared with values obtained directly by transhepatic sampling, both in the intact rat and in an isolated perfused rat liver preparation. 2. There was no agreement between estimates of the extraction ratio obtained by using the kinetic model and the directly measured values. 3. Elimination curves for Indocyanine Green were simulated to yield varied clearance values. Despite a 250% variation in clearance, extraction ratios derived using the two-compartment model were all greater than 0.9 and varied by less than 6%. 4. Estimates of liver blood flow obtained by deriving a value of the extraction ratio of Indocyanine Green using the two-compartment model are inaccurate.


1994 ◽  
Vol 266 (6) ◽  
pp. G1108-G1122 ◽  
Author(s):  
P. Ott ◽  
S. Keiding ◽  
A. H. Johnsen ◽  
L. Bass

In the anesthetized pig, we studied the kinetics after intravenous bolus injection of two fractions of indocyanine green (ICG): the genuine ICGg (95-99% of total) and a degradation product, ICGdp (1-5%). Plasma concentrations were followed in the carotid artery and a hepatic vein. ICGg disappearance curves (n = 7) were biexponential with rate constants alpha = 0.189 +/- 0.021 min-1 and beta = 0.0356 +/- 0.0061 min-1. The hepatic extraction fraction was constant with time. A detailed mathematical analysis showed this to be in disagreement with the conventional assumption that the biexponential plasma disappearance curve is a result of backflux from the liver storage to plasma. In contrast, our observations were predicted by an alternative model assuming temporary extrahepatic, extravasal redistribution during first-order, one-way hepatic uptake. Nevertheless, when a large bolus of sulfobromophthalein (BSP) was injected 20 min after ICG, a net backflux of ICG could be demonstrated, presumably due to countertransport. Thus a sufficient description of ICGg kinetics must include the complex kinetic behavior of the hepatic membrane carrier involved. Mass spectrometry suggested that ICGdp is formed by two ICGg molecules. Plasma elimination of ICGdp was slower (alpha = 0.0094 +/- 0.0007 min-1). Analysis of the bile after bolus injection (n = 2) of ICGdp revealed two possible metabolites of ICGdp that were not found in urine. Since BSP injection did not alter the ICGdp disappearance curve, ICGdp is probably not taken up by the same hepatic membrane carrier as ICGg.


2004 ◽  
Vol 286 (3) ◽  
pp. F590-F596 ◽  
Author(s):  
Zhonghua Qi ◽  
Irene Whitt ◽  
Amit Mehta ◽  
Jianping Jin ◽  
Min Zhao ◽  
...  

Two nonradioactive methods for determining glomerular filtration rate (GFR) in conscious mice using FITC-labeled inulin (FITC-inulin) were evaluated. The first method measured GFR using clearance kinetics of plasma FITC-inulin after a single bolus injection. Based on a two-compartment model, estimated GFR was 236.69 ± 16.55 and 140.20 ± 22.27 μl/min in male and female C57BL/6J mice, respectively. Total or ⅚ nephrectomy reduced inulin clearance to 0 or 32.80 ± 9.32 μl/min, respectively. Conversely, diabetes mellitus induced by streptozotocin was associated with increased GFR. The other approach measured urinary inulin clearance using intraperitoneal microosmotic pumps to deliver FITC-inulin and metabolic cages to collect timed urine samples. This approach yielded similar GFR values of 211.11 ± 26.56 and 157.36 ± 20.02 μl/min in male and female mice, respectively. These studies demonstrate the feasibility of repeated nonisotopic measurement of inulin clearance in conscious mice.


1981 ◽  
Vol 61 (3) ◽  
pp. 325-330 ◽  
Author(s):  
J. H. Marigold ◽  
I. T. Gilmore ◽  
R. P. H. Thompson

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min−1 m−2, range 376–672 increased to 704, 528–1968; P < 0.01) and indocyanine green (359, 227–473 increased to 435, 358–985; P < 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.


2005 ◽  
Author(s):  
Kishore Mosaliganti ◽  
Guang Jia ◽  
Johannes Heverhagen ◽  
raghu machiraju ◽  
Joel Saltz ◽  
...  

Dynamic magnetic resonance imaging (DCE-MRI) carried out with contrast media such as Gd-chelate complex (Gd-DTPA) allows the non-invasive assessment of microcirculatory characteristics of malignant lesions. Quantitative estimation of lesion parameters from the passage of the contrast media requires the use of pharmacokinetic two-compartment model. The input to the model is the time-intensity plot from a region of interest (ROI) covering the lesion extent. The lengthy imaging process, elasticity of the organs and patient movement result in complex deformations in the subject requiring 3D motion correction for ROI alignment. This paper presents results on applying the Thirion Demon’s 3D elastic matching procedure in the ITK framework on the two-compartment lesion parameters. Registration, meanwhile involves interpolation and smoothing operations thereby affecting the time-intensity plots. We explore the trade-offs that arise between registration and lesion parameter estimation. Experiments on synthesized and real deformation are presented.


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