title: Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Yang
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Yang
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Min-Ming
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Bo-Yin
authors.initials: BY
authors.lastname: Wang
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Jian-Feng Yang, Min-Ming Zhang, Department of Radiology, Second Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Bao-Chun
authors.initials: BC
authors.lastname: Lu
mesh_terms: D000368:Aged; D002199:Capillary Permeability; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012039:Regional Blood Flow; D047368:Tumor Burden
chemical_list: D003287:Contrast Media
keywords: Dynamic contrast-enhanced magnetic resonance imaging; Hepatocellular carcinoma; Pharmacokinetics