Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2016; 22(13): 3652-3662
Published online Apr 7, 2016. doi: 10.3748/wjg.v22.i13.3652
Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma
Jian-Feng Yang, Zhen-Hua Zhao, Yu Zhang, Li Zhao, Li-Ming Yang, Min-Ming Zhang, Bo-Yin Wang, Ting Wang, Bao-Chun Lu
Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
Jian-Feng Yang, Shaoxing People’s Hospital (Shaoxing Hospital of Zhejiang University), Shaoxing 312000, Zhejiang Province, China
Zhen-Hua Zhao, Yu Zhang, Li Zhao, Li-Ming Yang, Bo-Yin Wang, Ting Wang, Department of Radiology, Shaoxing People’s Hospital (Shaoxing Hospital of Zhejiang University), Shaoxing 312000, Zhejiang Province, China
Bao-Chun Lu, Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital of Zhejiang University), Shaoxing 312000, Zhejiang Province, China
Author contributions: Yang JF and Zhao ZH contributed equally to this work; Yang JF, Zhao ZH and Zhang MM designed the research; Zhang Y, Zhao L, Yang LM, Wang BY, Wang T and Lu BC performed the research; Zhang Y and Zhao L analyzed the data; and Yang JF wrote the paper.
Supported by Public Welfare Projects of Science Technology Department of Zhejiang Province, No. 2014C33151; Medical Research Programs of Zhejiang province, No. 2014KYA215, No. 2015KYB398, No. 2015RCA024 and No. 2015KYB403; and Research Projects of Public Technology Application of Science and Technology of Shaoxing City, No. 2013D10039.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Shaoxing People’s Hospital (Shaoxing Hospital of Zhejiang University).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Min-Ming Zhang, Professor, Chief, Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. zhangminming@zju.edu.cn
Telephone: +86-571-87315255 Fax: +86-571-87315255
Received: October 26, 2015
Peer-review started: October 27, 2015
First decision: December 11, 2015
Revised: December 15, 2015
Accepted: December 30, 2015
Article in press: December 30, 2015
Published online: April 7, 2016
Processing time: 153 Days and 18.3 Hours
Abstract

AIM: To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma (HCC).

METHODS: From January 2014 to April 2015, we prospectively measured and analyzed pharmacokinetic parameters [transfer constant (Ktrans), plasma flow (Fp), permeability surface area product (PS), efflux rate constant (kep), extravascular extracellular space volume ratio (ve), blood plasma volume ratio (vp), and hepatic perfusion index (HPI)] using dual-input two-compartment tracer kinetic models [a dual-input extended Tofts model and a dual-input 2-compartment exchange model (2CXM)] in 28 consecutive HCC patients. A well-known consensus that HCC is a hypervascular tumor supplied by the hepatic artery and the portal vein was used as a reference standard. A paired Student’s t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and Pearson correlation analysis was also applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by Pearson correlation analysis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by Spearman correlation analysis.

RESULTS: The Fp value was greater than the PS value (FP = 1.07 mL/mL per minute, PS = 0.19 mL/mL per minute) in the dual-input 2CXM; HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dual-input 2CXM, respectively. There were no significant differences in the kep, vp, or HPI between the dual-input extended Tofts model and the dual-input 2CXM (P = 0.524, 0.569, and 0.622, respectively). All equivalent pharmacokinetic parameters, except for ve, were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dual-input 2CXM were correlated with Ktrans derived from the dual-input extended Tofts model (P = 0.002, r = 0.566; P = 0.002, r = 0.570); kep, vp, and HPI between the two kinetic models were positively correlated (P = 0.001, r = 0.594; P = 0.0001, r = 0.686; P = 0.04, r = 0.391, respectively). In the dual input extended Tofts model, ve was significantly less than that in the dual input 2CXM (P = 0.004), and no significant correlation was seen between the two tracer kinetic models (P = 0.156, r = 0.276). Neither tumor size nor tumor stage was significantly correlated with any of the pharmacokinetic parameters obtained from the two models (P > 0.05).

CONCLUSION: A dual-input two-compartment pharmacokinetic model (a dual-input extended Tofts model and a dual-input 2CXM) can be used in assessing the microvascular physiopathological properties before the treatment of advanced HCC. The dual-input extended Tofts model may be more stable in measuring the ve; however, the dual-input 2CXM may be more detailed and accurate in measuring microvascular permeability.

Keywords: Hepatocellular carcinoma; Dynamic contrast-enhanced magnetic resonance imaging; Pharmacokinetics

Core tip: Dynamic contrast-enhanced magnetic resonance imaging provides a more comprehensive assessment of microvascular parameters in tumors; however, selection of a pharmacokinetic model that takes into account actual physiopathological status is an essential component of evaluating tumor microvascular permeability and perfusion. Here, we confirm that a dual-input two-compartment tracer kinetic model is suitable for evaluating microvascular properties in advanced hepatocellular carcinoma.