Comparison of Liver Perfusion Parameters Studied With Conventional Extravascular and Experimental Intravascular CT Contrast Agents

Rationale and Objectives

To compare liver perfusion parameters obtained by using an extravascular contrast agent and a blood-pool agent.

Materials and Methods

Fifteen rabbits were imaged with a continuous 40-second single-slice computed tomography acquisition after a bolus injection of contrast agent (physiologic bolus duration 4–5 seconds, extravascular iohexol, n = 7; experimental nanoparticulated blood-pool agent WIN8883, n = 8). Time-density curves were generated for the aorta, portal vein, and liver. From the curves, arterial, portal, and total blood flows and hepatic perfusion index (HPI, arterial-to-total perfusion ratio) were determined by using two commonly applied fundamentally different analyzing methods: the single-compartment model and the peak gradient (PG) method. Also, the gamma variate fitting method was used.

Results

By using the single-compartment model, the obtained HPI and total blood flow were 0.14 ± 0.04 and 2.29 ± 0.40 (mL/min/mL tissue ) for WIN8883, and 0.15 ± 0.06 ( P = .54) and 4.60 ± 1.14 (mL/min/mL tissue ) ( P = .0002) for iohexol, respectively. With the PG, HPI and total blood flow were 0.15 ± 0.08 and 1.27 ± 0.24 (mL/min/mL tissue ) for WIN8883, and 0.20 ± 0.06 ( P = .12) and 2.11 ± 0.25 (mL/min/mL tissue ) ( P = .00002) for iohexol, respectively. With the blood pool agent, similar contrast enhancement to the conventional agent was achieved with about 36% reduced dosage of iodine per body weight (mg I/kg).

Conclusions

HPI was found to be quite insensitive to different contrast agent types and analyzing methods. However, the arterial, portal and total liver blood flow values strongly depend on contrast agent type and modeling method.

The determination of liver perfusion has received increasing attention because most hepatic diseases cause alterations in perfusion conditions ( ). With liver metastases, these alterations seem to occur even before any structural changes become visible ( ). Perfusion computed tomography (CT) offers a clinical tool for the determination of both global and local perfusion changes within the liver with high spatial and temporal resolutions ( ). Measuring blood volume and flow with functional computed tomography (fCT) uses a modality specific marker introduced into the bloodstream coupled with mathematical modeling of the behavior of the marker as it circulates through the organ under investigation ( ). Validity to report physiologically meaningful perfusion parameters and the comparability of these parameters obtained with different imaging and analyzing procedures are important challenges in hepatic perfusion imaging ( ).

Clinically used iodinated CT contrast agents readily pass across the capillary membranes of most organs ( ). Contrast agents with their distribution limited to vascular space have been under development for CT ( ). With such agents, vascular-specific contrast is obtained in addition to long-lasting tissue enhancement. They also enable the use of simple and clinically attractive perfusion analyzing methodology. One of the most important questions for clinical practise is the relation of perfusion parameters obtained with conventional extravascular agents and intravascular contrast agents. Such comparable knowledge of these parameters with both agent types is potentially helpful in future studies conducted with either agent.

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Material and methods

Study Population and Contrast Material

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CT Scanning

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Data Analysis and Image Evaluation

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Results

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Table 1

Perfusion Parameters Obtained With Iohexol and WIN8883 by Using the Single-Compartment Model

F arterial F portal F total Hepatic Perfusion Index Mean Transit Time WIN8883 0.34 ± 0.13 1.95 ± 0.36 2.29 ± 0.40 0.14 ± 0.04 8.2 ± 1.8 Iohexol 0.67 ± 0.25 3.93 ± 1.08 4.60 ± 1.14 0.15 ± 0.06 7.0 ± 2.8P .007 .0005 .0002 .54 .85

The blood flows are given in mL/min/mL tissue and mean transit time in seconds.

Table 2

Perfusion Parameters Obtained With Iohexol and WIN8883 by Using the Peak Gradient (PG) Method

F arterial F portal F total Hepatic Perfusion Index WIN8883 0.20 ± 0.13 1.08 ± 0.20 1.27 ± 0.24 0.15 ± 0.08 Iohexol 0.43 ± 0.13 1.69 ± 0.25 2.11 ± 0.25 0.20 ± 0.06P .005 .0002 .00002 .12

The blood flows are given in mL/min/mL tissue .

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Table 3

Normalized Steepness (the Time Gradient Divided by the Peak Enhancement) of Aortic, Portal Vein, Hepatic Arterial, and Portal Phase Enhancement Curves

Aorta Portal Vein Arterial Phase Portal Phase WIN8883 0.72 ± 0.06 0.28 ± 0.06 0.29 ± 0.05 0.13 ± 0.04 Iohexol 0.66 ± 0.06 0.16 ± 0.03 0.32 ± 0.08 0.084 ± 0.008P .21 .006 .54 .03

The values are in s – 1 .

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Table 4

The Maximal ΔHU Values of the Enhancement Curves Measured From Aorta, Portal Vein, and Hepatic Arterial and Portal Phases

Aorta Portal Vein Arterial Phase Portal Phase WIN8883 1241 ± 657 272 ± 132 9.9 ± 3.1 38.5 ± 11.6 Iohexol 356 ± 44 67 ± 18 8.2 ± 3.4 24.6 ± 3.9P .007 .003 .37 .017

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Discussion

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Appendix 1

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VdC(t)dt=FACA(t)+FPCP(t)−VMTTC(t) V

(

)

(

)

(

)

−

MTT

(

)

V is the volume [mL tissue ] of the volume of interest (VOI); MTT is the mean transit time for the contrast agent to move through the VOI [seconds]; F A , F P , and F (= F A + F P ) [mL/second] are hepatic arterial, portal, and total blood flows; and C A ( t ), C P ( t ), and C ( t ) are the contrast material concentrations in the aorta, portal, vein, and the VOI, respectively. Morales and Smith ( ) have suggested that a contrast agent gradient between tissue input and output causes that a true blood flow is related to the obtained blood flow as F obtained = F true / r , with 0 ≤ r ≤ 1, resulting in that F obtained ≥ F true .

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F′V=dHtissue(t)dtHinput(t) F

′

(

)

(

)

where F ′ is arterial or portal blood flow [mL/second], H tissue is arterial or portal bolus phase ΔHU time data, and H input is ΔHU time data of arterial or portal phase bolus input measured from aorta or portal vein, respectively.

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F′V=Htissue(t)∫0tHinput(t)dt−∫0tHoutput(t)dt F

′

(

)

∫

(

)

−

∫

(

)

where integration is carried out from the beginning of the upslope of the bolus to the time t . For arterial blood flow, we integrated from zero to the maximum of arterial phase assuming no outflow. For portal blood flow, we integrated from zero to the 50% value of portal phase assuming no outflow. We also used outflow corrected version of this equation for WIN8883 by taking H output from the ΔHU time data measured from hepatic vein.

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MTT=VF MTT

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Comparison of Liver Perfusion Parameters Studied With Conventional Extravascular and Experimental Intravascular CT Contrast Agents

Rationale and Objectives

Materials and Methods

Results

Conclusions

Material and methods

Study Population and Contrast Material

CT Scanning

Data Analysis and Image Evaluation

Results

Discussion

Appendix 1

References

Further Reading

Abstracts of Funded National Institutes of Health Grants

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