Dataset Information

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy.

ABSTRACT:

Background

To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy.

Methods

Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (?), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (?C), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing.

Results

The WX-TK-model-derived ? (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived ?C (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS.

Conclusions

The WX-ETK-model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib.

SUBMITTER: Lee SH

PROVIDER: S-EPMC4569468 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy.

Lee Sang Ho SH Hayano Koichi K Zhu Andrew X AX Sahani Dushyant V DV Yoshida Hiroyuki H

PloS one 20150914 9

<h4>Background</h4>To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy.<h4>Methods</h4>Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two com ...[more]

PMID: 26366997

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Project description:Pulmonary perfusion with dynamic contrast-enhanced (DCE-) MRI is typically assessed using a single-input tracer kinetic model. Preliminary studies based on perfusion CT are indicating that dual-input perfusion modeling of lung tumors may be clinically valuable as lung tumors have a dual blood supply from the pulmonary and aortic system. This study aimed to investigate the feasibility of fitting dual-input tracer kinetic models to DCE-MRI datasets of thoracic malignancies, including malignant pleural mesothelioma (MPM) and nonsmall cell lung cancer (NSCLC), by comparing them to single-input (pulmonary or systemic arterial input) tracer kinetic models for the voxel-level analysis within the tumor with respect to goodness-of-fit statistics. Fifteen patients (five MPM, ten NSCLC) underwent DCE-MRI prior to radiotherapy. DCE-MRI data were analyzed using five different single- or dual-input tracer kinetic models: Tofts-Kety (TK), extended TK (ETK), two compartment exchange (2CX), adiabatic approximation to the tissue homogeneity (AATH) and distributed parameter (DP) models. The pulmonary blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), fractional interstitial volume (vI ), and volume transfer constant (KTrans ) were calculated for both single- and dual-input models. The pulmonary arterial flow fraction (?), pulmonary arterial blood flow (BFPA ) and systemic arterial blood flow (BFA ) were additionally calculated for only dual-input models. The competing models were ranked and their Akaike weights were calculated for each voxel according to corrected Akaike information criterion (cAIC). The optimal model was chosen based on the lowest cAIC value. In both types of tumors, all five dual-input models yielded lower cAIC values than their corresponding single-input models. The 2CX model was the best-fitted model and most optimal in describing tracer kinetic behavior to assess microvascular properties in both MPM and NSCLC. The dual-input 2CX-model-derived BFA was the most significant parameter in differentiating adenocarcinoma from squamous cell carcinoma histology for NSCLC patients.

Project description:PurposeTumor hypoxia is a major cause of radiation resistance, often present in various solid tumors. Dynamic [18 F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumor hypoxia. Comprehensive characterization of tumor microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters.MethodsThis study was done on head and neck cancer patients (N = 6), who were imaged dynamically with FMISO-PET and DCE-MRI on the same day. Images were registered and analyzed for kinetics on a voxel basis. FMISO-PET images were analyzed with the two-tissue compartment three rate-constant model. Additionally, tumor-to-muscle ratio (TMR) maps were evaluated. DCE-MRI was analyzed with the extended Tofts model. Voxel-wise Pearson's coefficients were calculated for each patient to assess pairwise parameter correlations.ResultsMedian correlations between FMISO uptake parameters and DCE-MRI kinetic parameters varied across the parameter pairs in the range from -0.05 to 0.71. The highest median correlation of r = 0.71 was observed for the pair Vb -vp , while the K1 -Ktrans median correlation was r = 0.45. Median correlation coefficients for the K1 -vp and the Ki -Ktrans pairs were r = 0.42 and r = 0.32, respectively. Correlations between FMISO uptake rate parameter Ki and DCE-MRI kinetic parameters varied substantially across the patients, whereas correlations between the FMISO and DCE-MRI vascular parameters were consistently high. Median TMR-K1 and TMR-Ktrans correlations were r = 0.52 and r = 0.46, respectively, but varied substantially across the patients.ConclusionsBased on this clinical evidence, we can conclude that the vascular fraction parameters obtained through DCE-MRI kinetic analysis or FMISO kinetic analysis measure the same biological property, while other kinetic parameters are unrelated. These results might be useful in the design of future clinical trials involving FMISO-PET/DCE-MR multimodality imaging for the assessment of tumor microenvironment.

Dataset Information

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy.

Background

Methods

Results

Conclusions

Publications

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy.

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