scholarly journals Validation of Microcirculatory Parameters Derived from the Standard Two-Compartment Model with Murine Xenografts Model

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Septian Hartono ◽  
Choon Hua Thng ◽  
Richard Weijie Ong ◽  
Quan Sing Ng ◽  
Tony Kiat Hon Lim ◽  
...  

The purpose of this study was to validate DCE-MRI parameters such as blood flow (F), permeability surface area product (PS), fractional intravascular space (v1), and fractional extracellular extravascular space (v2), obtained using a standard two-compartment model against other established analysis methods and histological indices. DCE-MRI datasets of 28 mice implanted with various human cancer xenografts were acquired and analyzed. Statistically significant correlations were found between the parameters derived from the standard two-compartment model (v1, v2, F, and PS) with the histological markers of intravascular and interstitial space and with the corresponding flow and permeability estimates obtained by the initial slope method and Patlak plot, respectively.

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S44-S51 ◽  
Author(s):  
Allan R. Andersen ◽  
Hans Friberg ◽  
Karen B. M. Knudsen ◽  
David I. Barry ◽  
Olaf B. Paulson ◽  
...  

The initial extraction ( E) across the blood–brain barrier (BBB) of [99mTc]– d,l-HM-PAO after intracarotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as the cotracer. In both series, cerebral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 μl), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF ( p < 0.001): With a small bolus of saline and at resting CBF (0.75 ml/g/min), E was 0.81, decreasing to 0.56 at a high CBF (1.5 ml/g/min). The calculated permeability surface area product ( PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p < 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 μl, while using a 120 μl bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood elements may reduce the apparent extraction across brain capillaries. In patients using a bolus of 1 ml saline, E decreased linearly with increasing CBF ( r = −0.81, p < 0.001). For a CBF of 0.59 ml/g/min and an average apparent E of 0.72, an apparent PS product of 0.76 ml/g/min was calculated. Analysis of the apparent E vs. time profiles indicated a backdiffusion of the tracer during the experimental period. This could lead to a small underestimation of the actual extraction values.


2015 ◽  
Vol 76 (3) ◽  
pp. 998-1006 ◽  
Author(s):  
Dimitra Flouri ◽  
Daniel Lesnic ◽  
Steven P. Sourbron

1994 ◽  
Vol 12 (6) ◽  
pp. 317-326 ◽  
Author(s):  
Masatomo Yashiro ◽  
Eri Muso ◽  
Munehiro Matsushima ◽  
Ryoichi Nagura ◽  
Kenji Sawanishi ◽  
...  

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.


1996 ◽  
Vol 40 (1) ◽  
pp. 105-109 ◽  
Author(s):  
M Dreetz ◽  
J Hamacher ◽  
J Eller ◽  
K Borner ◽  
P Koeppe ◽  
...  

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.


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