Dynamic Contrast-Enhanced and Diffusion-Weighted Magnetic Resonance Imaging Noninvasive Evaluation of Vascular Disrupting Treatment on Rabbit Liver Tumors

Haibo Shao,Xu Dai,Feng Chen,Yicheng Ni,Ziping Sun,Guoguang Fan,Jian Zhang,Ke Xu,Zhaohua Ding

doi:10.1371/journal.pone.0082649

Abstract

Evaluation of vascular disrupting treatment (VDT) is generally based on tumor size and enhancement on conventional magnetic resonance imaging (MRI) which, unfortunately, may be limited in providing satisfactory information. The purpose of the study is to evaluate consecutive changes of 20 rabbit VX2 liver tumors after VDT by dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) at a 3.0 T MR unit. Twenty four hours after intravenous injection of Combretastatin A-4-phosphate (CA4P) at 20 mg/kg, DCE-MRI derived Maximum Slope of Increase (MSI) and Positive Enhancement Integral (PEI) decreased sharply due to sudden shutting down of tumor feeding vessels. DWI derived Apparent Diffusion Coefficient (ADC) in tumor periphery decreased because of ischemic cell edema. On day 4, an increase of MSI was probably caused by the recovery of blood supply. A remarkable increase of ADC represented a large scale of necrosis among tumors. On day 8, the blood perfusion further decreased and the extent of necrosis further increased, reflected by lower MSI and PEI values and higher ADC value. On day 12, a second decrease of ADC was noticed because the re-growth of periphery tumor. The experimental data indicate that the therapeutic effects of VDT may be noninvasively monitored with DCE-MRI (reflecting tumor blood perfusion) and DWI (reflecting the changes of histology), which provide powerful measures for assessment of anticancer treatments.

Highlights

Tumor vascular targeting strategies can be divided into two different approaches
An alternative approach involves the application of therapeutics seeking the preferential destruction of the established tumor vessel network [4,5]. These vascular disrupting agents (VDAs) cause direct damage to the previously established tumor endothelium, resulting in a rapid and selective vascular shutdown and secondary tumor cell death caused by ischemia [6,7,8,9,10]
Evaluation of tumor response by imaging in these studies is generally based on tumor size and enhancement on conventional magnetic resonance imaging (MRI)

Summary

Introduction

Tumor vascular targeting strategies can be divided into two different approaches. Angiogenesis inhibitors (AIs) seek to inhibit the tumor-initiated angiogenic process by interrupting essential aspects of angiogenesis to prevent new blood vessel formation [1,2,3]. An alternative approach involves the application of therapeutics seeking the preferential destruction of the established tumor vessel network [4,5]. These vascular disrupting agents (VDAs) cause direct damage to the previously established tumor endothelium, resulting in a rapid and selective vascular shutdown and secondary tumor cell death caused by ischemia [6,7,8,9,10]. Imaging techniques may be limited in providing clinically satisfactory information about dynamic changes based on blood perfusion and extent of necrosis. Improvements of current imaging techniques play a critical role in finding the optimal strategy to determine treatment success and guide future therapy [18,19,20]

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