Date of Award

Fall 2006

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)


Biomedical Engineering

First Advisor

Schmainda, Kathleen M.

Second Advisor

Krouwer, Hendrikus, G. J.

Third Advisor

Kurpad, Shekar N.


Emerging concepts and evidence have purported that certain antiangiogenic drugs can transiently "normalize" the abnormal morphology and function of tumor vasculature. It is suggested that this transitory period of vascular "normalization" is suitable for drug delivery to the tumor microenvironment, and may improve the efficiency of chemotherapy or radiotherapy. From another perspective, this view seems rather counterintuitive since the normalization of tumor vasculature could potentially augment the growth rate of tumor. Understanding this process has significant implications for improving therapeutic outcomes. If normalization provides the best time during which treatment should be administered, we want to know when the normalization occurs, and how to optimize timing, dosing and possibly the combinations of drugs administered. If normalization results in advanced tumor growth, rather than a window of opportunity, we want to make sure treatment strategies avoid normalization as an endpoint. Most of the recent studies in rodent models have been invasive and involved different groups of rodents (i.e. serial studies). However, non-invasive imaging techniques are in great need to delineate vascular "normalization" in brain tumor of the same subject over time (i.e. longitudinal studies). So, we became motivated to implement advanced magnetic resonance imaging (MRI) methods to provide the information necessary to detect and characterize "normalization" and subsequently to optimize treatment strategies. The MRI methods, dynamic susceptibility contrast (DSC) imaging and dynamic contrast enhancement (DCE), can be use to assess the "normalization" window of the tumor vasculature during therapeutic intervention. These methods can be used to estimate the vascular morphology and vascular function of tumors.



Restricted Access Item

Having trouble?