All ETDs from UAB

Advisory Committee Chair

Thian C Ng

Advisory Committee Members

James A Posey III

Donald B Tweig

Document Type

Thesis

Date of Award

2007

Degree Name by School

Master of Science in Biomedical Engineering (MSBME) School of Engineering

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown to be a potentially useful tool for early prediction of tumor response to antiangiogenesis agents. In this study, the technique was used to evaluate the chemotherapeutic drug doxorubicin with or without the tyrosine kinase inhibitor sorafenib in patients with advanced hepatocellular carcinoma (HCC). Five male patients (ages 50 to 78 years, average age 67  8 years) were studied with serial T1-weighted DCE-MRI to measure the alteration of perfusion parameters of tumors in response to the treatment. All patients received doxorubicin at dose of 60 mg/m2 intravenously every 21 days. Among them, 3 patients also received sorafenib 400 mg orally twice daily, and 2 patients (control) received placebos. DCE-MRI studies at 3 T were performed one day before, and one week, 6 weeks and 12 weeks after therapies were started. The initial enhancement rate (ER) was calculated, and a general kinetic model was employed to fit the signal enhancement curve to generate the volume transfer constant (Ktrans). Histogram and mean perfusion analyses showed that both perfusion parameters Ktrans and ER in HCC tumors of the 3 patients receiving sorafenib and doxorubicin shifted to a lower cellular population distribution the first week after treatment and showed that the profiles of a large population distribution in low values remained similar at 6 and 12 iii weeks after treatments were started; These findings suggest that the antiangiogenic agent sorafenib is effective in these cases. One of these patients showed significant mass re-duction during this study. For this patient, the mean values of ER and Ktrans over the whole tumor region obtained before treatment and one week after treatment was begun were found to decrease from 0.23 s-1 to 0.15 s-1 and from 0.14 s-1 to 0.02 s-1, respectively. One patient treated with only doxorubicin exhibited significant decrease in perfusion pa-rameters, a result suggesting that this drug may have had an antiangiogenic effect in this patient. I have successfully accomplished both the implementation of in vivo DCE-MRI acquisition with the use of a high field 3T clinical scanner and the postprocessing of mul-tiple vascular and perfusion parameters with the use of the Matlab platform. The DCE-MRI results from the studies of HCC patients demonstrate that DCE-MRI is a sensitive biomarker for the early detection of the efficacy of antiangiogenic drugs.

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Engineering Commons

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