Access Type

Open Access Dissertation

Date of Award

1-1-2010

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

E M. Haacke

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive method used to evaluate the biological activity in early clinical trials of novel drugs targeting the tumor vasculature using gadolinium-DTPA (Gd) as a contrast agent. However, it has some limitations, such as reproducibility, data acquisition times, the presence of noise, extracting contrast concentration, estimating T1 relaxation and estimating pharmacokinetic parameters.

In this work, a new approach to used fixed T1(0) which provides more reproducible DCE results has been introduced. Using this new algorithm to quantify the vascular changes in DCE-MRI, a pre-clinical renal cell carcinoma (RCC) tumor model was used to demonstrate the ability of DCE-MRI to quantify the vascular changes induced by various doses of sunitinib in tumor-bearing kidneys and normal contralateral kidneys. Usually, only the first minute of data are used for processing to calculate the initial area under the curve (IAUC) and/or the median value of cumulative initial area under the curve (CIAUC) in order to monitor changes between pre and post drug treatment. However, in this work, the first two minutes was used to include the effect of the washout process of the kidneys. Moreover, DCE-MRI was used to investigate the vascular changes induced by pre-treatment with sunitinib in KCL-18 kidney tumors to schedule the initiation of chemotherapy. DCE results were confirmed with the histologic studies.

In this thesis, several new measures of vascular properties have been introduced, including: the fraction of active pixels (FAP); contrast agent uptake to the peak (AUCtp); time to peak concentration (TTP); washout slope (Nslope); as well as full width half maximum (FWHM) of IAUC. The results from the pre-clinical RCC tumor model demonstrate that DCE parametric maps have the potential to assess the effect of antiangiogenic drugs on blood flow and physiological vascular changes in tumors as well as normal tissues. These new parametric maps provided further guidance as to what could be considered normal versus abnormal tissue response to antiangiogenic therapy. The results of this research should lead to a clear improvement in the ability of DCE-MRI as a quantitative method to evaluate tumor vasculature and other hemodynamic properties.

Download

Share

COinS