Note
Go to the end to download the full example code.
Preclinical - repeat dosing effects on liver function#
This example illustrates the use of Liver for fitting of signals
measured in liver. The use case is provided by the liver work package of the
TRISTAN project which develops imaging
biomarkers for drug safety assessment. The manuscript relating to this data
and analysis is currently in preparation.
The specific objective of the study was to investigate the potential of gadoxetate-enhanced DCE-MRI to study acute inhibition of hepatocyte transporters of drug-induced liver injury (DILI) causing drugs, and to study potential changes in transporter function after chronic dosing.
The study presented here measured gadoxetate uptake and excretion in healthy rats scanned after administration of vehicle and repetitive dosing regimes of either Rifampicin, Cyclosporine, or Bosentan. Studies were performed in preclinical MRI scanners at 3 different centers and 2 different field strengths.
Reference
Mikael Montelius, Steven Sourbron, Nicola Melillo, Daniel Scotcher, Aleksandra Galetin, Gunnar Schuetz, Claudia Green, Edvin Johansson, John C. Waterton, and Paul Hockings. Acute and chronic rifampicin effect on gadoxetate uptake in rats using gadoxetate DCE-MRI. Int Soc Mag Reson Med 2021; 2674.
Setup#
# Import packages
import pandas as pd
import numpy as np
import matplotlib.pyplot as plt
import seaborn as sns
import dcmri as dc
# Fetch the data
data = dc.fetch('tristan_mdosing')
Model definition#
In order to avoid some repetition in this script, we define a function that returns a trained model for a single dataset.
The model uses a standardized, population-average input function and fits for only 2 parameters, fixing all other free parameters to typical values for this rat model:
def tristan_rat(data, **kwargs):
# High-resolution time points for prediction
t = np.arange(0, np.amax(data['time'])+0.5, 0.5)
# Standard input function
ca = dc.aif_tristan_rat(t, BAT=data['BAT'], duration=data['duration'])
# Liver model with population input function
model = dc.Liver(
# Input parameters
t = t,
ca = ca,
# Acquisition parameters
field_strength = data['field_strength'],
TR = data['TR'],
FA = data['FA'],
n0 = data['n0'],
# Kinetic paramaters
kinetics = '1I-IC-HF',
H = 0.418,
ve = 0.23,
free = {
'khe': [0, np.inf],
'Th': [0, np.inf],
},
# Tissue paramaters
R10 = 1/dc.T1(data['field_strength'], 'liver'),
)
return model.train(data['time'], data['liver'], **kwargs)
Check model fit#
Before running the full analysis on all cases, lets illustrate the results by fitting the baseline visit for the first subject. We use maximum verbosity to get some feedback about the iterations:
#model = tristan_rat(data[0], xtol=1e-3, verbose=2)
model = tristan_rat(data[0], xtol=1e-3, verbose=2)
Iteration Total nfev Cost Cost reduction Step norm Optimality
0 1 1.0128e+09 5.37e+10
1 3 8.9347e+08 1.19e+08 3.97e+02 6.21e+10
2 4 5.8888e+08 3.05e+08 7.01e+02 2.48e+11
3 5 4.1876e+08 1.70e+08 3.74e+01 1.80e+10
4 6 3.0475e+08 1.14e+08 3.64e+02 1.93e+11
5 7 4.3438e+07 2.61e+08 5.63e+01 3.92e+10
6 8 2.3882e+07 1.96e+07 1.63e+01 1.94e+07
7 9 2.3877e+07 4.84e+03 7.87e-01 3.92e+06
8 10 2.3877e+07 3.31e-01 4.72e-03 7.02e+02
`xtol` termination condition is satisfied.
Function evaluations 10, initial cost 1.0128e+09, final cost 2.3877e+07, first-order optimality 7.02e+02.
Plot the results to check that the model has fitted the data:
Print the measured model parameters and any derived parameters and check that standard deviations of measured parameters are small relative to the value, indicating that the parameters are measured reliably:
model.print_params(round_to=3)
--------------------------------
Free parameters with their stdev
--------------------------------
Hepatocellular uptake rate (khe): 0.011 (0.0) mL/sec/cm3
Hepatocellular mean transit time (Th): 260.882 (10.419) sec
----------------------------
Fixed and derived parameters
----------------------------
Hematocrit (H): 0.418
Liver extracellular volume fraction (ve): 0.23 mL/cm3
Biliary tissue excretion rate (Kbh): 0.004 mL/sec/cm3
Hepatocellular tissue uptake rate (Khe): 0.049 mL/sec/cm3
Biliary excretion rate (kbh): 0.003 mL/sec/cm3
Fit all data#
Now that we have illustrated an individual result in some detail, we proceed with fitting all the data. Results are stored in a dataframe in long format:
results = []
# Loop over all datasets
for scan in data:
# Generate a trained model for scan i:
model = tristan_rat(scan, xtol=1e-3)
# Save fitted parameters as a dataframe.
pars = model.export_params()
pars = pd.DataFrame.from_dict(pars,
orient = 'index',
columns = ["name", "value", "unit", 'stdev'])
pars['parameter'] = pars.index
pars['study'] = scan['study']
pars['visit'] = scan['visit']
pars['subject'] = scan['subject']
# Add the dataframe to the list of results
results.append(pars)
# Combine all results into a single dataframe.
results = pd.concat(results).reset_index(drop=True)
# Print all results
print(results.to_string())
name value unit stdev parameter study visit subject
0 Hematocrit 0.418000 0.000000 H 1 3 10
1 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 10
2 Hepatocellular uptake rate 0.011360 mL/sec/cm3 0.000423 khe 1 3 10
3 Hepatocellular mean transit time 260.881888 sec 10.418663 Th 1 3 10
4 Biliary tissue excretion rate 0.003833 mL/sec/cm3 0.000000 Kbh 1 3 10
5 Hepatocellular tissue uptake rate 0.049393 mL/sec/cm3 0.000000 Khe 1 3 10
6 Biliary excretion rate 0.002952 mL/sec/cm3 0.000000 kbh 1 3 10
7 Hematocrit 0.418000 0.000000 H 1 4 10
8 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 10
9 Hepatocellular uptake rate 0.010694 mL/sec/cm3 0.000376 khe 1 4 10
10 Hepatocellular mean transit time 366.054509 sec 14.497231 Th 1 4 10
11 Biliary tissue excretion rate 0.002732 mL/sec/cm3 0.000000 Kbh 1 4 10
12 Hepatocellular tissue uptake rate 0.046495 mL/sec/cm3 0.000000 Khe 1 4 10
13 Biliary excretion rate 0.002104 mL/sec/cm3 0.000000 kbh 1 4 10
14 Hematocrit 0.418000 0.000000 H 1 1 11
15 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 11
16 Hepatocellular uptake rate 0.013929 mL/sec/cm3 0.000628 khe 1 1 11
17 Hepatocellular mean transit time 424.375002 sec 22.004551 Th 1 1 11
18 Biliary tissue excretion rate 0.002356 mL/sec/cm3 0.000000 Kbh 1 1 11
19 Hepatocellular tissue uptake rate 0.060561 mL/sec/cm3 0.000000 Khe 1 1 11
20 Biliary excretion rate 0.001814 mL/sec/cm3 0.000000 kbh 1 1 11
21 Hematocrit 0.418000 0.000000 H 1 2 11
22 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 11
23 Hepatocellular uptake rate 0.001648 mL/sec/cm3 0.000185 khe 1 2 11
24 Hepatocellular mean transit time 2487.727225 sec 1055.364828 Th 1 2 11
25 Biliary tissue excretion rate 0.000402 mL/sec/cm3 0.000000 Kbh 1 2 11
26 Hepatocellular tissue uptake rate 0.007164 mL/sec/cm3 0.000000 Khe 1 2 11
27 Biliary excretion rate 0.000310 mL/sec/cm3 0.000000 kbh 1 2 11
28 Hematocrit 0.418000 0.000000 H 1 3 11
29 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 11
30 Hepatocellular uptake rate 0.002163 mL/sec/cm3 0.000281 khe 1 3 11
31 Hepatocellular mean transit time 965.450684 sec 224.974883 Th 1 3 11
32 Biliary tissue excretion rate 0.001036 mL/sec/cm3 0.000000 Kbh 1 3 11
33 Hepatocellular tissue uptake rate 0.009402 mL/sec/cm3 0.000000 Khe 1 3 11
34 Biliary excretion rate 0.000798 mL/sec/cm3 0.000000 kbh 1 3 11
35 Hematocrit 0.418000 0.000000 H 1 4 11
36 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 11
37 Hepatocellular uptake rate 0.004936 mL/sec/cm3 0.000208 khe 1 4 11
38 Hepatocellular mean transit time 596.073557 sec 34.084226 Th 1 4 11
39 Biliary tissue excretion rate 0.001678 mL/sec/cm3 0.000000 Kbh 1 4 11
40 Hepatocellular tissue uptake rate 0.021463 mL/sec/cm3 0.000000 Khe 1 4 11
41 Biliary excretion rate 0.001292 mL/sec/cm3 0.000000 kbh 1 4 11
42 Hematocrit 0.418000 0.000000 H 1 1 12
43 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 12
44 Hepatocellular uptake rate 0.014488 mL/sec/cm3 0.000771 khe 1 1 12
45 Hepatocellular mean transit time 417.269572 sec 25.326947 Th 1 1 12
46 Biliary tissue excretion rate 0.002397 mL/sec/cm3 0.000000 Kbh 1 1 12
47 Hepatocellular tissue uptake rate 0.062990 mL/sec/cm3 0.000000 Khe 1 1 12
48 Biliary excretion rate 0.001845 mL/sec/cm3 0.000000 kbh 1 1 12
49 Hematocrit 0.418000 0.000000 H 1 2 12
50 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 12
51 Hepatocellular uptake rate 0.014446 mL/sec/cm3 0.000451 khe 1 2 12
52 Hepatocellular mean transit time 337.211463 sec 11.461603 Th 1 2 12
53 Biliary tissue excretion rate 0.002965 mL/sec/cm3 0.000000 Kbh 1 2 12
54 Hepatocellular tissue uptake rate 0.062808 mL/sec/cm3 0.000000 Khe 1 2 12
55 Biliary excretion rate 0.002283 mL/sec/cm3 0.000000 kbh 1 2 12
56 Hematocrit 0.418000 0.000000 H 1 3 12
57 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 12
58 Hepatocellular uptake rate 0.011003 mL/sec/cm3 0.000370 khe 1 3 12
59 Hepatocellular mean transit time 431.927755 sec 17.035747 Th 1 3 12
60 Biliary tissue excretion rate 0.002315 mL/sec/cm3 0.000000 Kbh 1 3 12
61 Hepatocellular tissue uptake rate 0.047839 mL/sec/cm3 0.000000 Khe 1 3 12
62 Biliary excretion rate 0.001783 mL/sec/cm3 0.000000 kbh 1 3 12
63 Hematocrit 0.418000 0.000000 H 1 4 12
64 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 12
65 Hepatocellular uptake rate 0.013862 mL/sec/cm3 0.000475 khe 1 4 12
66 Hepatocellular mean transit time 466.547133 sec 18.929658 Th 1 4 12
67 Biliary tissue excretion rate 0.002143 mL/sec/cm3 0.000000 Kbh 1 4 12
68 Hepatocellular tissue uptake rate 0.060268 mL/sec/cm3 0.000000 Khe 1 4 12
69 Biliary excretion rate 0.001650 mL/sec/cm3 0.000000 kbh 1 4 12
70 Hematocrit 0.418000 0.000000 H 1 1 1
71 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 1
72 Hepatocellular uptake rate 0.009421 mL/sec/cm3 0.000282 khe 1 1 1
73 Hepatocellular mean transit time 455.976198 sec 16.359730 Th 1 1 1
74 Biliary tissue excretion rate 0.002193 mL/sec/cm3 0.000000 Kbh 1 1 1
75 Hepatocellular tissue uptake rate 0.040961 mL/sec/cm3 0.000000 Khe 1 1 1
76 Biliary excretion rate 0.001689 mL/sec/cm3 0.000000 kbh 1 1 1
77 Hematocrit 0.418000 0.000000 H 1 2 1
78 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 1
79 Hepatocellular uptake rate 0.004239 mL/sec/cm3 0.000210 khe 1 2 1
80 Hepatocellular mean transit time 701.069187 sec 51.108464 Th 1 2 1
81 Biliary tissue excretion rate 0.001426 mL/sec/cm3 0.000000 Kbh 1 2 1
82 Hepatocellular tissue uptake rate 0.018431 mL/sec/cm3 0.000000 Khe 1 2 1
83 Biliary excretion rate 0.001098 mL/sec/cm3 0.000000 kbh 1 2 1
84 Hematocrit 0.418000 0.000000 H 1 3 1
85 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 1
86 Hepatocellular uptake rate 0.008431 mL/sec/cm3 0.000488 khe 1 3 1
87 Hepatocellular mean transit time 313.419030 sec 21.175651 Th 1 3 1
88 Biliary tissue excretion rate 0.003191 mL/sec/cm3 0.000000 Kbh 1 3 1
89 Hepatocellular tissue uptake rate 0.036658 mL/sec/cm3 0.000000 Khe 1 3 1
90 Biliary excretion rate 0.002457 mL/sec/cm3 0.000000 kbh 1 3 1
91 Hematocrit 0.418000 0.000000 H 1 4 1
92 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 1
93 Hepatocellular uptake rate 0.014041 mL/sec/cm3 0.000899 khe 1 4 1
94 Hepatocellular mean transit time 384.897687 sec 27.614715 Th 1 4 1
95 Biliary tissue excretion rate 0.002598 mL/sec/cm3 0.000000 Kbh 1 4 1
96 Hepatocellular tissue uptake rate 0.061047 mL/sec/cm3 0.000000 Khe 1 4 1
97 Biliary excretion rate 0.002001 mL/sec/cm3 0.000000 kbh 1 4 1
98 Hematocrit 0.418000 0.000000 H 1 1 2
99 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 2
100 Hepatocellular uptake rate 0.011729 mL/sec/cm3 0.000527 khe 1 1 2
101 Hepatocellular mean transit time 484.725752 sec 26.380592 Th 1 1 2
102 Biliary tissue excretion rate 0.002063 mL/sec/cm3 0.000000 Kbh 1 1 2
103 Hepatocellular tissue uptake rate 0.050996 mL/sec/cm3 0.000000 Khe 1 1 2
104 Biliary excretion rate 0.001589 mL/sec/cm3 0.000000 kbh 1 1 2
105 Hematocrit 0.418000 0.000000 H 1 2 2
106 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 2
107 Hepatocellular uptake rate 0.003668 mL/sec/cm3 0.000227 khe 1 2 2
108 Hepatocellular mean transit time 1054.167547 sec 124.051836 Th 1 2 2
109 Biliary tissue excretion rate 0.000949 mL/sec/cm3 0.000000 Kbh 1 2 2
110 Hepatocellular tissue uptake rate 0.015949 mL/sec/cm3 0.000000 Khe 1 2 2
111 Biliary excretion rate 0.000730 mL/sec/cm3 0.000000 kbh 1 2 2
112 Hematocrit 0.418000 0.000000 H 1 3 2
113 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 2
114 Hepatocellular uptake rate 0.004694 mL/sec/cm3 0.000381 khe 1 3 2
115 Hepatocellular mean transit time 697.642779 sec 83.085664 Th 1 3 2
116 Biliary tissue excretion rate 0.001433 mL/sec/cm3 0.000000 Kbh 1 3 2
117 Hepatocellular tissue uptake rate 0.020409 mL/sec/cm3 0.000000 Khe 1 3 2
118 Biliary excretion rate 0.001104 mL/sec/cm3 0.000000 kbh 1 3 2
119 Hematocrit 0.418000 0.000000 H 1 4 2
120 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 2
121 Hepatocellular uptake rate 0.015398 mL/sec/cm3 0.000560 khe 1 4 2
122 Hepatocellular mean transit time 315.509802 sec 12.316806 Th 1 4 2
123 Biliary tissue excretion rate 0.003169 mL/sec/cm3 0.000000 Kbh 1 4 2
124 Hepatocellular tissue uptake rate 0.066947 mL/sec/cm3 0.000000 Khe 1 4 2
125 Biliary excretion rate 0.002440 mL/sec/cm3 0.000000 kbh 1 4 2
126 Hematocrit 0.418000 0.000000 H 1 1 3
127 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 3
128 Hepatocellular uptake rate 0.019519 mL/sec/cm3 0.000883 khe 1 1 3
129 Hepatocellular mean transit time 312.731644 sec 14.896586 Th 1 1 3
130 Biliary tissue excretion rate 0.003198 mL/sec/cm3 0.000000 Kbh 1 1 3
131 Hepatocellular tissue uptake rate 0.084863 mL/sec/cm3 0.000000 Khe 1 1 3
132 Biliary excretion rate 0.002462 mL/sec/cm3 0.000000 kbh 1 1 3
133 Hematocrit 0.418000 0.000000 H 1 2 3
134 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 3
135 Hepatocellular uptake rate 0.015384 mL/sec/cm3 0.000736 khe 1 2 3
136 Hepatocellular mean transit time 327.292492 sec 16.897858 Th 1 2 3
137 Biliary tissue excretion rate 0.003055 mL/sec/cm3 0.000000 Kbh 1 2 3
138 Hepatocellular tissue uptake rate 0.066885 mL/sec/cm3 0.000000 Khe 1 2 3
139 Biliary excretion rate 0.002353 mL/sec/cm3 0.000000 kbh 1 2 3
140 Hematocrit 0.418000 0.000000 H 1 3 3
141 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 3
142 Hepatocellular uptake rate 0.012785 mL/sec/cm3 0.000771 khe 1 3 3
143 Hepatocellular mean transit time 395.362741 sec 27.063476 Th 1 3 3
144 Biliary tissue excretion rate 0.002529 mL/sec/cm3 0.000000 Kbh 1 3 3
145 Hepatocellular tissue uptake rate 0.055588 mL/sec/cm3 0.000000 Khe 1 3 3
146 Biliary excretion rate 0.001948 mL/sec/cm3 0.000000 kbh 1 3 3
147 Hematocrit 0.418000 0.000000 H 1 4 3
148 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 3
149 Hepatocellular uptake rate 0.015981 mL/sec/cm3 0.000860 khe 1 4 3
150 Hepatocellular mean transit time 348.756416 sec 20.418697 Th 1 4 3
151 Biliary tissue excretion rate 0.002867 mL/sec/cm3 0.000000 Kbh 1 4 3
152 Hepatocellular tissue uptake rate 0.069483 mL/sec/cm3 0.000000 Khe 1 4 3
153 Biliary excretion rate 0.002208 mL/sec/cm3 0.000000 kbh 1 4 3
154 Hematocrit 0.418000 0.000000 H 1 1 4
155 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 4
156 Hepatocellular uptake rate 0.002570 mL/sec/cm3 0.000264 khe 1 1 4
157 Hepatocellular mean transit time 427.138764 sec 53.709765 Th 1 1 4
158 Biliary tissue excretion rate 0.002341 mL/sec/cm3 0.000000 Kbh 1 1 4
159 Hepatocellular tissue uptake rate 0.011172 mL/sec/cm3 0.000000 Khe 1 1 4
160 Biliary excretion rate 0.001803 mL/sec/cm3 0.000000 kbh 1 1 4
161 Hematocrit 0.418000 0.000000 H 1 2 4
162 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 4
163 Hepatocellular uptake rate 0.004742 mL/sec/cm3 0.000301 khe 1 2 4
164 Hepatocellular mean transit time 510.073394 sec 41.386830 Th 1 2 4
165 Biliary tissue excretion rate 0.001961 mL/sec/cm3 0.000000 Kbh 1 2 4
166 Hepatocellular tissue uptake rate 0.020618 mL/sec/cm3 0.000000 Khe 1 2 4
167 Biliary excretion rate 0.001510 mL/sec/cm3 0.000000 kbh 1 2 4
168 Hematocrit 0.418000 0.000000 H 1 3 4
169 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 4
170 Hepatocellular uptake rate 0.014605 mL/sec/cm3 0.000652 khe 1 3 4
171 Hepatocellular mean transit time 280.643774 sec 13.311467 Th 1 3 4
172 Biliary tissue excretion rate 0.003563 mL/sec/cm3 0.000000 Kbh 1 3 4
173 Hepatocellular tissue uptake rate 0.063501 mL/sec/cm3 0.000000 Khe 1 3 4
174 Biliary excretion rate 0.002744 mL/sec/cm3 0.000000 kbh 1 3 4
175 Hematocrit 0.418000 0.000000 H 1 4 4
176 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 4
177 Hepatocellular uptake rate 0.004105 mL/sec/cm3 0.000335 khe 1 4 4
178 Hepatocellular mean transit time 389.894552 sec 37.662703 Th 1 4 4
179 Biliary tissue excretion rate 0.002565 mL/sec/cm3 0.000000 Kbh 1 4 4
180 Hepatocellular tissue uptake rate 0.017849 mL/sec/cm3 0.000000 Khe 1 4 4
181 Biliary excretion rate 0.001975 mL/sec/cm3 0.000000 kbh 1 4 4
182 Hematocrit 0.418000 0.000000 H 1 1 5
183 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 5
184 Hepatocellular uptake rate 0.011727 mL/sec/cm3 0.000566 khe 1 1 5
185 Hepatocellular mean transit time 445.224064 sec 25.319526 Th 1 1 5
186 Biliary tissue excretion rate 0.002246 mL/sec/cm3 0.000000 Kbh 1 1 5
187 Hepatocellular tissue uptake rate 0.050986 mL/sec/cm3 0.000000 Khe 1 1 5
188 Biliary excretion rate 0.001729 mL/sec/cm3 0.000000 kbh 1 1 5
189 Hematocrit 0.418000 0.000000 H 1 2 5
190 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 5
191 Hepatocellular uptake rate 0.002716 mL/sec/cm3 0.000258 khe 1 2 5
192 Hepatocellular mean transit time 1419.978564 sec 318.812190 Th 1 2 5
193 Biliary tissue excretion rate 0.000704 mL/sec/cm3 0.000000 Kbh 1 2 5
194 Hepatocellular tissue uptake rate 0.011807 mL/sec/cm3 0.000000 Khe 1 2 5
195 Biliary excretion rate 0.000542 mL/sec/cm3 0.000000 kbh 1 2 5
196 Hematocrit 0.418000 0.000000 H 1 3 5
197 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 5
198 Hepatocellular uptake rate 0.009439 mL/sec/cm3 0.000286 khe 1 3 5
199 Hepatocellular mean transit time 429.890843 sec 15.354736 Th 1 3 5
200 Biliary tissue excretion rate 0.002326 mL/sec/cm3 0.000000 Kbh 1 3 5
201 Hepatocellular tissue uptake rate 0.041041 mL/sec/cm3 0.000000 Khe 1 3 5
202 Biliary excretion rate 0.001791 mL/sec/cm3 0.000000 kbh 1 3 5
203 Hematocrit 0.418000 0.000000 H 1 4 5
204 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 5
205 Hepatocellular uptake rate 0.015926 mL/sec/cm3 0.000838 khe 1 4 5
206 Hepatocellular mean transit time 372.829327 sec 21.645639 Th 1 4 5
207 Biliary tissue excretion rate 0.002682 mL/sec/cm3 0.000000 Kbh 1 4 5
208 Hepatocellular tissue uptake rate 0.069246 mL/sec/cm3 0.000000 Khe 1 4 5
209 Biliary excretion rate 0.002065 mL/sec/cm3 0.000000 kbh 1 4 5
210 Hematocrit 0.418000 0.000000 H 1 1 6
211 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 6
212 Hepatocellular uptake rate 0.018883 mL/sec/cm3 0.000931 khe 1 1 6
213 Hepatocellular mean transit time 249.868614 sec 12.730263 Th 1 1 6
214 Biliary tissue excretion rate 0.004002 mL/sec/cm3 0.000000 Kbh 1 1 6
215 Hepatocellular tissue uptake rate 0.082101 mL/sec/cm3 0.000000 Khe 1 1 6
216 Biliary excretion rate 0.003082 mL/sec/cm3 0.000000 kbh 1 1 6
217 Hematocrit 0.418000 0.000000 H 1 2 6
218 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 6
219 Hepatocellular uptake rate 0.014291 mL/sec/cm3 0.000861 khe 1 2 6
220 Hepatocellular mean transit time 242.572870 sec 15.375428 Th 1 2 6
221 Biliary tissue excretion rate 0.004122 mL/sec/cm3 0.000000 Kbh 1 2 6
222 Hepatocellular tissue uptake rate 0.062136 mL/sec/cm3 0.000000 Khe 1 2 6
223 Biliary excretion rate 0.003174 mL/sec/cm3 0.000000 kbh 1 2 6
224 Hematocrit 0.418000 0.000000 H 1 3 6
225 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 6
226 Hepatocellular uptake rate 0.006593 mL/sec/cm3 0.000439 khe 1 3 6
227 Hepatocellular mean transit time 325.322720 sec 24.436474 Th 1 3 6
228 Biliary tissue excretion rate 0.003074 mL/sec/cm3 0.000000 Kbh 1 3 6
229 Hepatocellular tissue uptake rate 0.028664 mL/sec/cm3 0.000000 Khe 1 3 6
230 Biliary excretion rate 0.002367 mL/sec/cm3 0.000000 kbh 1 3 6
231 Hematocrit 0.418000 0.000000 H 1 4 6
232 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 6
233 Hepatocellular uptake rate 0.016688 mL/sec/cm3 0.000662 khe 1 4 6
234 Hepatocellular mean transit time 191.785580 sec 7.847247 Th 1 4 6
235 Biliary tissue excretion rate 0.005214 mL/sec/cm3 0.000000 Kbh 1 4 6
236 Hepatocellular tissue uptake rate 0.072555 mL/sec/cm3 0.000000 Khe 1 4 6
237 Biliary excretion rate 0.004015 mL/sec/cm3 0.000000 kbh 1 4 6
238 Hematocrit 0.418000 0.000000 H 1 1 7
239 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 7
240 Hepatocellular uptake rate 0.011046 mL/sec/cm3 0.000534 khe 1 1 7
241 Hepatocellular mean transit time 294.844598 sec 15.502774 Th 1 1 7
242 Biliary tissue excretion rate 0.003392 mL/sec/cm3 0.000000 Kbh 1 1 7
243 Hepatocellular tissue uptake rate 0.048025 mL/sec/cm3 0.000000 Khe 1 1 7
244 Biliary excretion rate 0.002612 mL/sec/cm3 0.000000 kbh 1 1 7
245 Hematocrit 0.418000 0.000000 H 1 2 7
246 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 7
247 Hepatocellular uptake rate 0.006140 mL/sec/cm3 0.000433 khe 1 2 7
248 Hepatocellular mean transit time 534.934817 sec 48.699611 Th 1 2 7
249 Biliary tissue excretion rate 0.001869 mL/sec/cm3 0.000000 Kbh 1 2 7
250 Hepatocellular tissue uptake rate 0.026697 mL/sec/cm3 0.000000 Khe 1 2 7
251 Biliary excretion rate 0.001439 mL/sec/cm3 0.000000 kbh 1 2 7
252 Hematocrit 0.418000 0.000000 H 1 3 7
253 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 7
254 Hepatocellular uptake rate 0.007300 mL/sec/cm3 0.000256 khe 1 3 7
255 Hepatocellular mean transit time 346.765820 sec 13.814794 Th 1 3 7
256 Biliary tissue excretion rate 0.002884 mL/sec/cm3 0.000000 Kbh 1 3 7
257 Hepatocellular tissue uptake rate 0.031737 mL/sec/cm3 0.000000 Khe 1 3 7
258 Biliary excretion rate 0.002221 mL/sec/cm3 0.000000 kbh 1 3 7
259 Hematocrit 0.418000 0.000000 H 1 4 7
260 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 7
261 Hepatocellular uptake rate 0.011719 mL/sec/cm3 0.000494 khe 1 4 7
262 Hepatocellular mean transit time 413.526302 sec 20.117422 Th 1 4 7
263 Biliary tissue excretion rate 0.002418 mL/sec/cm3 0.000000 Kbh 1 4 7
264 Hepatocellular tissue uptake rate 0.050951 mL/sec/cm3 0.000000 Khe 1 4 7
265 Biliary excretion rate 0.001862 mL/sec/cm3 0.000000 kbh 1 4 7
266 Hematocrit 0.418000 0.000000 H 1 1 8
267 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 8
268 Hepatocellular uptake rate 0.011670 mL/sec/cm3 0.000705 khe 1 1 8
269 Hepatocellular mean transit time 348.268073 sec 23.368511 Th 1 1 8
270 Biliary tissue excretion rate 0.002871 mL/sec/cm3 0.000000 Kbh 1 1 8
271 Hepatocellular tissue uptake rate 0.050740 mL/sec/cm3 0.000000 Khe 1 1 8
272 Biliary excretion rate 0.002211 mL/sec/cm3 0.000000 kbh 1 1 8
273 Hematocrit 0.418000 0.000000 H 1 2 8
274 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 8
275 Hepatocellular uptake rate 0.002659 mL/sec/cm3 0.000293 khe 1 2 8
276 Hepatocellular mean transit time 967.558918 sec 191.541817 Th 1 2 8
277 Biliary tissue excretion rate 0.001034 mL/sec/cm3 0.000000 Kbh 1 2 8
278 Hepatocellular tissue uptake rate 0.011563 mL/sec/cm3 0.000000 Khe 1 2 8
279 Biliary excretion rate 0.000796 mL/sec/cm3 0.000000 kbh 1 2 8
280 Hematocrit 0.418000 0.000000 H 1 3 8
281 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 8
282 Hepatocellular uptake rate 0.010515 mL/sec/cm3 0.000420 khe 1 3 8
283 Hepatocellular mean transit time 425.802086 sec 19.891952 Th 1 3 8
284 Biliary tissue excretion rate 0.002349 mL/sec/cm3 0.000000 Kbh 1 3 8
285 Hepatocellular tissue uptake rate 0.045718 mL/sec/cm3 0.000000 Khe 1 3 8
286 Biliary excretion rate 0.001808 mL/sec/cm3 0.000000 kbh 1 3 8
287 Hematocrit 0.418000 0.000000 H 1 4 8
288 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 8
289 Hepatocellular uptake rate 0.009289 mL/sec/cm3 0.000357 khe 1 4 8
290 Hepatocellular mean transit time 488.900526 sec 23.084646 Th 1 4 8
291 Biliary tissue excretion rate 0.002045 mL/sec/cm3 0.000000 Kbh 1 4 8
292 Hepatocellular tissue uptake rate 0.040389 mL/sec/cm3 0.000000 Khe 1 4 8
293 Biliary excretion rate 0.001575 mL/sec/cm3 0.000000 kbh 1 4 8
294 Hematocrit 0.418000 0.000000 H 1 1 9
295 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 1 9
296 Hepatocellular uptake rate 0.008269 mL/sec/cm3 0.000232 khe 1 1 9
297 Hepatocellular mean transit time 325.545479 sec 10.218068 Th 1 1 9
298 Biliary tissue excretion rate 0.003072 mL/sec/cm3 0.000000 Kbh 1 1 9
299 Hepatocellular tissue uptake rate 0.035951 mL/sec/cm3 0.000000 Khe 1 1 9
300 Biliary excretion rate 0.002365 mL/sec/cm3 0.000000 kbh 1 1 9
301 Hematocrit 0.418000 0.000000 H 1 2 9
302 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 2 9
303 Hepatocellular uptake rate 0.008248 mL/sec/cm3 0.000258 khe 1 2 9
304 Hepatocellular mean transit time 340.651061 sec 11.989710 Th 1 2 9
305 Biliary tissue excretion rate 0.002936 mL/sec/cm3 0.000000 Kbh 1 2 9
306 Hepatocellular tissue uptake rate 0.035860 mL/sec/cm3 0.000000 Khe 1 2 9
307 Biliary excretion rate 0.002260 mL/sec/cm3 0.000000 kbh 1 2 9
308 Hematocrit 0.418000 0.000000 H 1 3 9
309 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 3 9
310 Hepatocellular uptake rate 0.011018 mL/sec/cm3 0.000610 khe 1 3 9
311 Hepatocellular mean transit time 349.011046 sec 21.531700 Th 1 3 9
312 Biliary tissue excretion rate 0.002865 mL/sec/cm3 0.000000 Kbh 1 3 9
313 Hepatocellular tissue uptake rate 0.047905 mL/sec/cm3 0.000000 Khe 1 3 9
314 Biliary excretion rate 0.002206 mL/sec/cm3 0.000000 kbh 1 3 9
315 Hematocrit 0.418000 0.000000 H 1 4 9
316 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 1 4 9
317 Hepatocellular uptake rate 0.011872 mL/sec/cm3 0.000497 khe 1 4 9
318 Hepatocellular mean transit time 397.282304 sec 18.991896 Th 1 4 9
319 Biliary tissue excretion rate 0.002517 mL/sec/cm3 0.000000 Kbh 1 4 9
320 Hepatocellular tissue uptake rate 0.051619 mL/sec/cm3 0.000000 Khe 1 4 9
321 Biliary excretion rate 0.001938 mL/sec/cm3 0.000000 kbh 1 4 9
322 Hematocrit 0.418000 0.000000 H 2 1 10
323 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 10
324 Hepatocellular uptake rate 0.033112 mL/sec/cm3 0.003861 khe 2 1 10
325 Hepatocellular mean transit time 235.620024 sec 28.921416 Th 2 1 10
326 Biliary tissue excretion rate 0.004244 mL/sec/cm3 0.000000 Kbh 2 1 10
327 Hepatocellular tissue uptake rate 0.143965 mL/sec/cm3 0.000000 Khe 2 1 10
328 Biliary excretion rate 0.003268 mL/sec/cm3 0.000000 kbh 2 1 10
329 Hematocrit 0.418000 0.000000 H 2 2 10
330 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 10
331 Hepatocellular uptake rate 0.046997 mL/sec/cm3 0.006581 khe 2 2 10
332 Hepatocellular mean transit time 189.261962 sec 26.924762 Th 2 2 10
333 Biliary tissue excretion rate 0.005284 mL/sec/cm3 0.000000 Kbh 2 2 10
334 Hepatocellular tissue uptake rate 0.204333 mL/sec/cm3 0.000000 Khe 2 2 10
335 Biliary excretion rate 0.004068 mL/sec/cm3 0.000000 kbh 2 2 10
336 Hematocrit 0.418000 0.000000 H 2 3 10
337 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 10
338 Hepatocellular uptake rate 0.039437 mL/sec/cm3 0.005774 khe 2 3 10
339 Hepatocellular mean transit time 201.532747 sec 30.441740 Th 2 3 10
340 Biliary tissue excretion rate 0.004962 mL/sec/cm3 0.000000 Kbh 2 3 10
341 Hepatocellular tissue uptake rate 0.171465 mL/sec/cm3 0.000000 Khe 2 3 10
342 Biliary excretion rate 0.003821 mL/sec/cm3 0.000000 kbh 2 3 10
343 Hematocrit 0.418000 0.000000 H 2 1 11
344 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 11
345 Hepatocellular uptake rate 0.021184 mL/sec/cm3 0.001626 khe 2 1 11
346 Hepatocellular mean transit time 296.420460 sec 25.207575 Th 2 1 11
347 Biliary tissue excretion rate 0.003374 mL/sec/cm3 0.000000 Kbh 2 1 11
348 Hepatocellular tissue uptake rate 0.092103 mL/sec/cm3 0.000000 Khe 2 1 11
349 Biliary excretion rate 0.002598 mL/sec/cm3 0.000000 kbh 2 1 11
350 Hematocrit 0.418000 0.000000 H 2 2 11
351 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 11
352 Hepatocellular uptake rate 0.001947 mL/sec/cm3 0.000388 khe 2 2 11
353 Hepatocellular mean transit time 994.000498 sec 383.078666 Th 2 2 11
354 Biliary tissue excretion rate 0.001006 mL/sec/cm3 0.000000 Kbh 2 2 11
355 Hepatocellular tissue uptake rate 0.008463 mL/sec/cm3 0.000000 Khe 2 2 11
356 Biliary excretion rate 0.000775 mL/sec/cm3 0.000000 kbh 2 2 11
357 Hematocrit 0.418000 0.000000 H 2 3 11
358 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 11
359 Hepatocellular uptake rate 0.003697 mL/sec/cm3 0.000553 khe 2 3 11
360 Hepatocellular mean transit time 738.371001 sec 176.773271 Th 2 3 11
361 Biliary tissue excretion rate 0.001354 mL/sec/cm3 0.000000 Kbh 2 3 11
362 Hepatocellular tissue uptake rate 0.016075 mL/sec/cm3 0.000000 Khe 2 3 11
363 Biliary excretion rate 0.001043 mL/sec/cm3 0.000000 kbh 2 3 11
364 Hematocrit 0.418000 0.000000 H 2 1 12
365 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 12
366 Hepatocellular uptake rate 0.033331 mL/sec/cm3 0.002803 khe 2 1 12
367 Hepatocellular mean transit time 327.775686 sec 30.151847 Th 2 1 12
368 Biliary tissue excretion rate 0.003051 mL/sec/cm3 0.000000 Kbh 2 1 12
369 Hepatocellular tissue uptake rate 0.144918 mL/sec/cm3 0.000000 Khe 2 1 12
370 Biliary excretion rate 0.002349 mL/sec/cm3 0.000000 kbh 2 1 12
371 Hematocrit 0.418000 0.000000 H 2 2 12
372 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 12
373 Hepatocellular uptake rate 0.004196 mL/sec/cm3 0.000621 khe 2 2 12
374 Hepatocellular mean transit time 767.727313 sec 185.616425 Th 2 2 12
375 Biliary tissue excretion rate 0.001303 mL/sec/cm3 0.000000 Kbh 2 2 12
376 Hepatocellular tissue uptake rate 0.018242 mL/sec/cm3 0.000000 Khe 2 2 12
377 Biliary excretion rate 0.001003 mL/sec/cm3 0.000000 kbh 2 2 12
378 Hematocrit 0.418000 0.000000 H 2 3 12
379 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 12
380 Hepatocellular uptake rate 0.003780 mL/sec/cm3 0.000617 khe 2 3 12
381 Hepatocellular mean transit time 875.317163 sec 253.321504 Th 2 3 12
382 Biliary tissue excretion rate 0.001142 mL/sec/cm3 0.000000 Kbh 2 3 12
383 Hepatocellular tissue uptake rate 0.016436 mL/sec/cm3 0.000000 Khe 2 3 12
384 Biliary excretion rate 0.000880 mL/sec/cm3 0.000000 kbh 2 3 12
385 Hematocrit 0.418000 0.000000 H 2 1 13
386 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 13
387 Hepatocellular uptake rate 0.039150 mL/sec/cm3 0.004911 khe 2 1 13
388 Hepatocellular mean transit time 204.471388 sec 26.489246 Th 2 1 13
389 Biliary tissue excretion rate 0.004891 mL/sec/cm3 0.000000 Kbh 2 1 13
390 Hepatocellular tissue uptake rate 0.170218 mL/sec/cm3 0.000000 Khe 2 1 13
391 Biliary excretion rate 0.003766 mL/sec/cm3 0.000000 kbh 2 1 13
392 Hematocrit 0.418000 0.000000 H 2 2 13
393 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 13
394 Hepatocellular uptake rate 0.003361 mL/sec/cm3 0.000460 khe 2 2 13
395 Hepatocellular mean transit time 682.319533 sec 143.183808 Th 2 2 13
396 Biliary tissue excretion rate 0.001466 mL/sec/cm3 0.000000 Kbh 2 2 13
397 Hepatocellular tissue uptake rate 0.014611 mL/sec/cm3 0.000000 Khe 2 2 13
398 Biliary excretion rate 0.001129 mL/sec/cm3 0.000000 kbh 2 2 13
399 Hematocrit 0.418000 0.000000 H 2 1 1
400 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 1
401 Hepatocellular uptake rate 0.021234 mL/sec/cm3 0.001323 khe 2 1 1
402 Hepatocellular mean transit time 445.709125 sec 33.837966 Th 2 1 1
403 Biliary tissue excretion rate 0.002244 mL/sec/cm3 0.000000 Kbh 2 1 1
404 Hepatocellular tissue uptake rate 0.092321 mL/sec/cm3 0.000000 Khe 2 1 1
405 Biliary excretion rate 0.001728 mL/sec/cm3 0.000000 kbh 2 1 1
406 Hematocrit 0.418000 0.000000 H 2 2 1
407 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 1
408 Hepatocellular uptake rate 0.001764 mL/sec/cm3 0.000209 khe 2 2 1
409 Hepatocellular mean transit time 946.697311 sec 210.231871 Th 2 2 1
410 Biliary tissue excretion rate 0.001056 mL/sec/cm3 0.000000 Kbh 2 2 1
411 Hepatocellular tissue uptake rate 0.007668 mL/sec/cm3 0.000000 Khe 2 2 1
412 Biliary excretion rate 0.000813 mL/sec/cm3 0.000000 kbh 2 2 1
413 Hematocrit 0.418000 0.000000 H 2 1 2
414 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 2
415 Hepatocellular uptake rate 0.025439 mL/sec/cm3 0.001669 khe 2 1 2
416 Hepatocellular mean transit time 400.946896 sec 30.716632 Th 2 1 2
417 Biliary tissue excretion rate 0.002494 mL/sec/cm3 0.000000 Kbh 2 1 2
418 Hepatocellular tissue uptake rate 0.110604 mL/sec/cm3 0.000000 Khe 2 1 2
419 Biliary excretion rate 0.001920 mL/sec/cm3 0.000000 kbh 2 1 2
420 Hematocrit 0.418000 0.000000 H 2 2 2
421 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 2
422 Hepatocellular uptake rate 0.003262 mL/sec/cm3 0.000459 khe 2 2 2
423 Hepatocellular mean transit time 811.695441 sec 193.168158 Th 2 2 2
424 Biliary tissue excretion rate 0.001232 mL/sec/cm3 0.000000 Kbh 2 2 2
425 Hepatocellular tissue uptake rate 0.014184 mL/sec/cm3 0.000000 Khe 2 2 2
426 Biliary excretion rate 0.000949 mL/sec/cm3 0.000000 kbh 2 2 2
427 Hematocrit 0.418000 0.000000 H 2 3 2
428 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 2
429 Hepatocellular uptake rate 0.002429 mL/sec/cm3 0.000334 khe 2 3 2
430 Hepatocellular mean transit time 1235.243836 sec 382.791656 Th 2 3 2
431 Biliary tissue excretion rate 0.000810 mL/sec/cm3 0.000000 Kbh 2 3 2
432 Hepatocellular tissue uptake rate 0.010561 mL/sec/cm3 0.000000 Khe 2 3 2
433 Biliary excretion rate 0.000623 mL/sec/cm3 0.000000 kbh 2 3 2
434 Hematocrit 0.418000 0.000000 H 2 1 3
435 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 3
436 Hepatocellular uptake rate 0.029708 mL/sec/cm3 0.001956 khe 2 1 3
437 Hepatocellular mean transit time 319.881225 sec 23.125250 Th 2 1 3
438 Biliary tissue excretion rate 0.003126 mL/sec/cm3 0.000000 Kbh 2 1 3
439 Hepatocellular tissue uptake rate 0.129164 mL/sec/cm3 0.000000 Khe 2 1 3
440 Biliary excretion rate 0.002407 mL/sec/cm3 0.000000 kbh 2 1 3
441 Hematocrit 0.418000 0.000000 H 2 2 3
442 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 3
443 Hepatocellular uptake rate 0.038069 mL/sec/cm3 0.004001 khe 2 2 3
444 Hepatocellular mean transit time 241.038074 sec 26.431877 Th 2 2 3
445 Biliary tissue excretion rate 0.004149 mL/sec/cm3 0.000000 Kbh 2 2 3
446 Hepatocellular tissue uptake rate 0.165518 mL/sec/cm3 0.000000 Khe 2 2 3
447 Biliary excretion rate 0.003195 mL/sec/cm3 0.000000 kbh 2 2 3
448 Hematocrit 0.418000 0.000000 H 2 3 3
449 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 3
450 Hepatocellular uptake rate 0.039354 mL/sec/cm3 0.003759 khe 2 3 3
451 Hepatocellular mean transit time 291.082102 sec 29.463169 Th 2 3 3
452 Biliary tissue excretion rate 0.003435 mL/sec/cm3 0.000000 Kbh 2 3 3
453 Hepatocellular tissue uptake rate 0.171103 mL/sec/cm3 0.000000 Khe 2 3 3
454 Biliary excretion rate 0.002645 mL/sec/cm3 0.000000 kbh 2 3 3
455 Hematocrit 0.418000 0.000000 H 2 1 4
456 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 4
457 Hepatocellular uptake rate 0.034651 mL/sec/cm3 0.003536 khe 2 1 4
458 Hepatocellular mean transit time 271.868035 sec 29.462149 Th 2 1 4
459 Biliary tissue excretion rate 0.003678 mL/sec/cm3 0.000000 Kbh 2 1 4
460 Hepatocellular tissue uptake rate 0.150656 mL/sec/cm3 0.000000 Khe 2 1 4
461 Biliary excretion rate 0.002832 mL/sec/cm3 0.000000 kbh 2 1 4
462 Hematocrit 0.418000 0.000000 H 2 2 4
463 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 4
464 Hepatocellular uptake rate 0.041785 mL/sec/cm3 0.003907 khe 2 2 4
465 Hepatocellular mean transit time 277.735620 sec 27.220410 Th 2 2 4
466 Biliary tissue excretion rate 0.003601 mL/sec/cm3 0.000000 Kbh 2 2 4
467 Hepatocellular tissue uptake rate 0.181673 mL/sec/cm3 0.000000 Khe 2 2 4
468 Biliary excretion rate 0.002772 mL/sec/cm3 0.000000 kbh 2 2 4
469 Hematocrit 0.418000 0.000000 H 2 3 4
470 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 4
471 Hepatocellular uptake rate 0.045374 mL/sec/cm3 0.004490 khe 2 3 4
472 Hepatocellular mean transit time 303.252561 sec 31.581094 Th 2 3 4
473 Biliary tissue excretion rate 0.003298 mL/sec/cm3 0.000000 Kbh 2 3 4
474 Hepatocellular tissue uptake rate 0.197278 mL/sec/cm3 0.000000 Khe 2 3 4
475 Biliary excretion rate 0.002539 mL/sec/cm3 0.000000 kbh 2 3 4
476 Hematocrit 0.418000 0.000000 H 2 1 5
477 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 5
478 Hepatocellular uptake rate 0.029670 mL/sec/cm3 0.002393 khe 2 1 5
479 Hepatocellular mean transit time 339.699622 sec 30.432673 Th 2 1 5
480 Biliary tissue excretion rate 0.002944 mL/sec/cm3 0.000000 Kbh 2 1 5
481 Hepatocellular tissue uptake rate 0.128999 mL/sec/cm3 0.000000 Khe 2 1 5
482 Biliary excretion rate 0.002267 mL/sec/cm3 0.000000 kbh 2 1 5
483 Hematocrit 0.418000 0.000000 H 2 2 5
484 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 5
485 Hepatocellular uptake rate 0.026065 mL/sec/cm3 0.002304 khe 2 2 5
486 Hepatocellular mean transit time 343.631652 sec 34.102096 Th 2 2 5
487 Biliary tissue excretion rate 0.002910 mL/sec/cm3 0.000000 Kbh 2 2 5
488 Hepatocellular tissue uptake rate 0.113325 mL/sec/cm3 0.000000 Khe 2 2 5
489 Biliary excretion rate 0.002241 mL/sec/cm3 0.000000 kbh 2 2 5
490 Hematocrit 0.418000 0.000000 H 2 3 5
491 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 5
492 Hepatocellular uptake rate 0.028257 mL/sec/cm3 0.001605 khe 2 3 5
493 Hepatocellular mean transit time 390.260253 sec 24.879173 Th 2 3 5
494 Biliary tissue excretion rate 0.002562 mL/sec/cm3 0.000000 Kbh 2 3 5
495 Hepatocellular tissue uptake rate 0.122858 mL/sec/cm3 0.000000 Khe 2 3 5
496 Biliary excretion rate 0.001973 mL/sec/cm3 0.000000 kbh 2 3 5
497 Hematocrit 0.418000 0.000000 H 2 1 6
498 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 6
499 Hepatocellular uptake rate 0.032433 mL/sec/cm3 0.003232 khe 2 1 6
500 Hepatocellular mean transit time 307.557296 sec 33.235168 Th 2 1 6
501 Biliary tissue excretion rate 0.003251 mL/sec/cm3 0.000000 Kbh 2 1 6
502 Hepatocellular tissue uptake rate 0.141014 mL/sec/cm3 0.000000 Khe 2 1 6
503 Biliary excretion rate 0.002504 mL/sec/cm3 0.000000 kbh 2 1 6
504 Hematocrit 0.418000 0.000000 H 2 2 6
505 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 6
506 Hepatocellular uptake rate 0.037131 mL/sec/cm3 0.003858 khe 2 2 6
507 Hepatocellular mean transit time 255.163021 sec 27.837065 Th 2 2 6
508 Biliary tissue excretion rate 0.003919 mL/sec/cm3 0.000000 Kbh 2 2 6
509 Hepatocellular tissue uptake rate 0.161437 mL/sec/cm3 0.000000 Khe 2 2 6
510 Biliary excretion rate 0.003018 mL/sec/cm3 0.000000 kbh 2 2 6
511 Hematocrit 0.418000 0.000000 H 2 3 6
512 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 6
513 Hepatocellular uptake rate 0.041152 mL/sec/cm3 0.003960 khe 2 3 6
514 Hepatocellular mean transit time 292.157416 sec 29.693316 Th 2 3 6
515 Biliary tissue excretion rate 0.003423 mL/sec/cm3 0.000000 Kbh 2 3 6
516 Hepatocellular tissue uptake rate 0.178921 mL/sec/cm3 0.000000 Khe 2 3 6
517 Biliary excretion rate 0.002636 mL/sec/cm3 0.000000 kbh 2 3 6
518 Hematocrit 0.418000 0.000000 H 2 1 7
519 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 7
520 Hepatocellular uptake rate 0.024099 mL/sec/cm3 0.001930 khe 2 1 7
521 Hepatocellular mean transit time 384.292751 sec 35.641988 Th 2 1 7
522 Biliary tissue excretion rate 0.002602 mL/sec/cm3 0.000000 Kbh 2 1 7
523 Hepatocellular tissue uptake rate 0.104778 mL/sec/cm3 0.000000 Khe 2 1 7
524 Biliary excretion rate 0.002004 mL/sec/cm3 0.000000 kbh 2 1 7
525 Hematocrit 0.418000 0.000000 H 2 2 7
526 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 7
527 Hepatocellular uptake rate 0.002941 mL/sec/cm3 0.000483 khe 2 2 7
528 Hepatocellular mean transit time 811.928946 sec 225.756469 Th 2 2 7
529 Biliary tissue excretion rate 0.001232 mL/sec/cm3 0.000000 Kbh 2 2 7
530 Hepatocellular tissue uptake rate 0.012786 mL/sec/cm3 0.000000 Khe 2 2 7
531 Biliary excretion rate 0.000948 mL/sec/cm3 0.000000 kbh 2 2 7
532 Hematocrit 0.418000 0.000000 H 2 3 7
533 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 7
534 Hepatocellular uptake rate 0.003205 mL/sec/cm3 0.000451 khe 2 3 7
535 Hepatocellular mean transit time 949.340030 sec 249.605449 Th 2 3 7
536 Biliary tissue excretion rate 0.001053 mL/sec/cm3 0.000000 Kbh 2 3 7
537 Hepatocellular tissue uptake rate 0.013937 mL/sec/cm3 0.000000 Khe 2 3 7
538 Biliary excretion rate 0.000811 mL/sec/cm3 0.000000 kbh 2 3 7
539 Hematocrit 0.418000 0.000000 H 2 1 8
540 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 8
541 Hepatocellular uptake rate 0.027113 mL/sec/cm3 0.002562 khe 2 1 8
542 Hepatocellular mean transit time 357.212389 sec 38.121451 Th 2 1 8
543 Biliary tissue excretion rate 0.002799 mL/sec/cm3 0.000000 Kbh 2 1 8
544 Hepatocellular tissue uptake rate 0.117884 mL/sec/cm3 0.000000 Khe 2 1 8
545 Biliary excretion rate 0.002156 mL/sec/cm3 0.000000 kbh 2 1 8
546 Hematocrit 0.418000 0.000000 H 2 2 8
547 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 8
548 Hepatocellular uptake rate 0.003043 mL/sec/cm3 0.000517 khe 2 2 8
549 Hepatocellular mean transit time 671.614983 sec 173.618331 Th 2 2 8
550 Biliary tissue excretion rate 0.001489 mL/sec/cm3 0.000000 Kbh 2 2 8
551 Hepatocellular tissue uptake rate 0.013229 mL/sec/cm3 0.000000 Khe 2 2 8
552 Biliary excretion rate 0.001146 mL/sec/cm3 0.000000 kbh 2 2 8
553 Hematocrit 0.418000 0.000000 H 2 3 8
554 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 8
555 Hepatocellular uptake rate 0.005026 mL/sec/cm3 0.000595 khe 2 3 8
556 Hepatocellular mean transit time 833.169027 sec 168.968813 Th 2 3 8
557 Biliary tissue excretion rate 0.001200 mL/sec/cm3 0.000000 Kbh 2 3 8
558 Hepatocellular tissue uptake rate 0.021854 mL/sec/cm3 0.000000 Khe 2 3 8
559 Biliary excretion rate 0.000924 mL/sec/cm3 0.000000 kbh 2 3 8
560 Hematocrit 0.418000 0.000000 H 2 1 9
561 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 1 9
562 Hepatocellular uptake rate 0.023804 mL/sec/cm3 0.001659 khe 2 1 9
563 Hepatocellular mean transit time 295.900874 sec 22.692724 Th 2 1 9
564 Biliary tissue excretion rate 0.003380 mL/sec/cm3 0.000000 Kbh 2 1 9
565 Hepatocellular tissue uptake rate 0.103497 mL/sec/cm3 0.000000 Khe 2 1 9
566 Biliary excretion rate 0.002602 mL/sec/cm3 0.000000 kbh 2 1 9
567 Hematocrit 0.418000 0.000000 H 2 2 9
568 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 2 9
569 Hepatocellular uptake rate 0.038737 mL/sec/cm3 0.005048 khe 2 2 9
570 Hepatocellular mean transit time 216.494162 sec 29.223576 Th 2 2 9
571 Biliary tissue excretion rate 0.004619 mL/sec/cm3 0.000000 Kbh 2 2 9
572 Hepatocellular tissue uptake rate 0.168423 mL/sec/cm3 0.000000 Khe 2 2 9
573 Biliary excretion rate 0.003557 mL/sec/cm3 0.000000 kbh 2 2 9
574 Hematocrit 0.418000 0.000000 H 2 3 9
575 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 2 3 9
576 Hepatocellular uptake rate 0.025780 mL/sec/cm3 0.001996 khe 2 3 9
577 Hepatocellular mean transit time 337.643064 sec 29.263491 Th 2 3 9
578 Biliary tissue excretion rate 0.002962 mL/sec/cm3 0.000000 Kbh 2 3 9
579 Hepatocellular tissue uptake rate 0.112088 mL/sec/cm3 0.000000 Khe 2 3 9
580 Biliary excretion rate 0.002281 mL/sec/cm3 0.000000 kbh 2 3 9
581 Hematocrit 0.418000 0.000000 H 3 1 1
582 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 1 1
583 Hepatocellular uptake rate 0.013878 mL/sec/cm3 0.000871 khe 3 1 1
584 Hepatocellular mean transit time 221.663872 sec 15.373636 Th 3 1 1
585 Biliary tissue excretion rate 0.004511 mL/sec/cm3 0.000000 Kbh 3 1 1
586 Hepatocellular tissue uptake rate 0.060339 mL/sec/cm3 0.000000 Khe 3 1 1
587 Biliary excretion rate 0.003474 mL/sec/cm3 0.000000 kbh 3 1 1
588 Hematocrit 0.418000 0.000000 H 3 2 1
589 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 2 1
590 Hepatocellular uptake rate 0.020542 mL/sec/cm3 0.001571 khe 3 2 1
591 Hepatocellular mean transit time 247.053382 sec 20.756601 Th 3 2 1
592 Biliary tissue excretion rate 0.004048 mL/sec/cm3 0.000000 Kbh 3 2 1
593 Hepatocellular tissue uptake rate 0.089313 mL/sec/cm3 0.000000 Khe 3 2 1
594 Biliary excretion rate 0.003117 mL/sec/cm3 0.000000 kbh 3 2 1
595 Hematocrit 0.418000 0.000000 H 3 1 2
596 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 1 2
597 Hepatocellular uptake rate 0.024471 mL/sec/cm3 0.001575 khe 3 1 2
598 Hepatocellular mean transit time 302.324666 sec 21.708634 Th 3 1 2
599 Biliary tissue excretion rate 0.003308 mL/sec/cm3 0.000000 Kbh 3 1 2
600 Hepatocellular tissue uptake rate 0.106395 mL/sec/cm3 0.000000 Khe 3 1 2
601 Biliary excretion rate 0.002547 mL/sec/cm3 0.000000 kbh 3 1 2
602 Hematocrit 0.418000 0.000000 H 3 2 2
603 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 2 2
604 Hepatocellular uptake rate 0.022383 mL/sec/cm3 0.001349 khe 3 2 2
605 Hepatocellular mean transit time 288.271988 sec 19.335446 Th 3 2 2
606 Biliary tissue excretion rate 0.003469 mL/sec/cm3 0.000000 Kbh 3 2 2
607 Hepatocellular tissue uptake rate 0.097316 mL/sec/cm3 0.000000 Khe 3 2 2
608 Biliary excretion rate 0.002671 mL/sec/cm3 0.000000 kbh 3 2 2
609 Hematocrit 0.418000 0.000000 H 3 1 3
610 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 1 3
611 Hepatocellular uptake rate 0.030478 mL/sec/cm3 0.002652 khe 3 1 3
612 Hepatocellular mean transit time 224.327038 sec 20.889863 Th 3 1 3
613 Biliary tissue excretion rate 0.004458 mL/sec/cm3 0.000000 Kbh 3 1 3
614 Hepatocellular tissue uptake rate 0.132512 mL/sec/cm3 0.000000 Khe 3 1 3
615 Biliary excretion rate 0.003432 mL/sec/cm3 0.000000 kbh 3 1 3
616 Hematocrit 0.418000 0.000000 H 3 2 3
617 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 2 3
618 Hepatocellular uptake rate 0.038609 mL/sec/cm3 0.003628 khe 3 2 3
619 Hepatocellular mean transit time 224.923479 sec 22.292314 Th 3 2 3
620 Biliary tissue excretion rate 0.004446 mL/sec/cm3 0.000000 Kbh 3 2 3
621 Hepatocellular tissue uptake rate 0.167863 mL/sec/cm3 0.000000 Khe 3 2 3
622 Biliary excretion rate 0.003423 mL/sec/cm3 0.000000 kbh 3 2 3
623 Hematocrit 0.418000 0.000000 H 3 1 4
624 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 1 4
625 Hepatocellular uptake rate 0.025619 mL/sec/cm3 0.002110 khe 3 1 4
626 Hepatocellular mean transit time 248.559512 sec 22.275827 Th 3 1 4
627 Biliary tissue excretion rate 0.004023 mL/sec/cm3 0.000000 Kbh 3 1 4
628 Hepatocellular tissue uptake rate 0.111385 mL/sec/cm3 0.000000 Khe 3 1 4
629 Biliary excretion rate 0.003098 mL/sec/cm3 0.000000 kbh 3 1 4
630 Hematocrit 0.418000 0.000000 H 3 2 4
631 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 2 4
632 Hepatocellular uptake rate 0.016949 mL/sec/cm3 0.001533 khe 3 2 4
633 Hepatocellular mean transit time 205.938968 sec 20.350920 Th 3 2 4
634 Biliary tissue excretion rate 0.004856 mL/sec/cm3 0.000000 Kbh 3 2 4
635 Hepatocellular tissue uptake rate 0.073691 mL/sec/cm3 0.000000 Khe 3 2 4
636 Biliary excretion rate 0.003739 mL/sec/cm3 0.000000 kbh 3 2 4
637 Hematocrit 0.418000 0.000000 H 3 1 5
638 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 1 5
639 Hepatocellular uptake rate 0.027619 mL/sec/cm3 0.002204 khe 3 1 5
640 Hepatocellular mean transit time 286.618569 sec 25.162528 Th 3 1 5
641 Biliary tissue excretion rate 0.003489 mL/sec/cm3 0.000000 Kbh 3 1 5
642 Hepatocellular tissue uptake rate 0.120082 mL/sec/cm3 0.000000 Khe 3 1 5
643 Biliary excretion rate 0.002686 mL/sec/cm3 0.000000 kbh 3 1 5
644 Hematocrit 0.418000 0.000000 H 3 2 5
645 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 2 5
646 Hepatocellular uptake rate 0.022092 mL/sec/cm3 0.001436 khe 3 2 5
647 Hepatocellular mean transit time 280.771730 sec 20.256932 Th 3 2 5
648 Biliary tissue excretion rate 0.003562 mL/sec/cm3 0.000000 Kbh 3 2 5
649 Hepatocellular tissue uptake rate 0.096051 mL/sec/cm3 0.000000 Khe 3 2 5
650 Biliary excretion rate 0.002742 mL/sec/cm3 0.000000 kbh 3 2 5
651 Hematocrit 0.418000 0.000000 H 3 1 6
652 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 1 6
653 Hepatocellular uptake rate 0.031736 mL/sec/cm3 0.002392 khe 3 1 6
654 Hepatocellular mean transit time 258.546517 sec 21.028975 Th 3 1 6
655 Biliary tissue excretion rate 0.003868 mL/sec/cm3 0.000000 Kbh 3 1 6
656 Hepatocellular tissue uptake rate 0.137984 mL/sec/cm3 0.000000 Khe 3 1 6
657 Biliary excretion rate 0.002978 mL/sec/cm3 0.000000 kbh 3 1 6
658 Hematocrit 0.418000 0.000000 H 3 2 6
659 Liver extracellular volume fraction 0.230000 mL/cm3 0.000000 ve 3 2 6
660 Hepatocellular uptake rate 0.022781 mL/sec/cm3 0.001649 khe 3 2 6
661 Hepatocellular mean transit time 283.462777 sec 22.764106 Th 3 2 6
662 Biliary tissue excretion rate 0.003528 mL/sec/cm3 0.000000 Kbh 3 2 6
663 Hepatocellular tissue uptake rate 0.099049 mL/sec/cm3 0.000000 Khe 3 2 6
664 Biliary excretion rate 0.002716 mL/sec/cm3 0.000000 kbh 3 2 6
Plot individual results#
Now let’s plot the biomarker values across visits for each study group. For this exercise, let’s specify khe and kbh as the biomarker parameters that we are interested in. For each subject, we can visualise the change in biomarker values between visits. For reference, in the below plots, the studies are numbered as follows: Study 1: Rifampicin repetitive dosing regime Study 2: Cyclosporine repetitive dosing regime Study 3: Bosentan repetitive dosing regime
# Customise plot settings
plt.rcParams["axes.titlesize"] = 25
plt.rcParams["axes.labelsize"] = 20
plt.rcParams["axes.labelweight"] = 'bold'
plt.rcParams["axes.titleweight"] = 'bold'
plt.rcParams["font.weight"] = 'bold'
plt.rc('axes', linewidth=1.5)
plt.rc('xtick', labelsize=15)
plt.rc('ytick', labelsize=15)
plt.rcParams["lines.linewidth"] = 1.5
plt.rcParams['lines.markersize'] = 2
# Extract results of interest, i.e., for parameters khe and kbh
filtered_data = results.query("parameter == 'khe' | parameter == 'kbh'")
# Plot distributions across visits per study groups and per biomarker
g = sns.catplot(data=filtered_data,
x='visit',
y='value',
palette='rocket',
hue='subject',
row='parameter',
col='study',
kind='point',
sharey=False)
g.set_titles(pad=15) # increase white space between subplots and titles
# Set limits for y-axes
for i in range(0, 3):
g.axes[0, i].set(ylim=([0, 0.05]))
for i in range(0, 3):
g.axes[1, i].set(ylim=([0, 0.005]))
g.set_ylabels("Value [mL/sec/cm3]") # set labels for y-axis
# reposition legend
sns.move_legend(g, "lower right", bbox_to_anchor=(0.95, 0.7))
plt.tight_layout()
plt.show()
# Choose the last image as a thumbnail for the gallery
# sphinx_gallery_thumbnail_number = -1
Total running time of the script: (0 minutes 48.950 seconds)