Abstract: Motexafin Gadolinium (MGd) is an investigational radiation enhancer that has tumor-specific uptake. Furthermore, it is detectable by Magnetic Resonance Imaging (MRI) because the gadolinium within its molecular framework enhances the proton spin longitudinal relaxation of water molecules that can bind to it. In this dissertation research, MRI data that were collected in a Phase I clinical trial in which MGd was administered to glioblastoma multiforme (GBM) patients during standard radiation therapy (RT) were evaluated to answer the following five questions: (1) Does MGd cross the intact blood brain barrier? (2) Is MGd retained in tumor when the trial's dosing regimen was used? (3) How does MGd-induced enhancement of tumor MRI signal compare with that produced by a conventional MRI contrast agent? (4) Did MGd treatment during RT improve survival in GBM patients? (5) Can MRI relaxometry be used to obtain intratumoral MGd concentration? MGd-induced signal enhancement in T1-weighted magnetic resonance (MR) images was used to address questions 1 and 2. T1-weighted MR images obtained after administration of MGd were quantitatively compared to similar images obtained after administration of a conventional MRI contrast agent, gadodiamide (Omniscan®), in the same patients to address question 3. Kaplan-Meier survival analysis was used to answer question 4 with an UCLA clinical glioma database as case-matched controls. Question 5 was addressed by generating quantitative multi-parametric MR images from the raw images obtained during the trial. The findings are as follows: (1) MGd does not cross the intact blood brain barrier. (2) The dosing and maintenance regimen used in the trial were appropriate to maintain stable tumor MGd levels during RT. (3) MGd is less efficient than gadodiamide as an MRI contrast agent for GBM. (4) MGd administration in combination with RT failed to show survival benefit compared with RT alone. (5) Relaxometry maps were successfully generated and provided an estimate of tumor MGd concentrations.