Date of Award


Degree Type


Degree Name

Doctor of Philosophy


A contrast enhanced CT method was developed for measuring the blood-brain permeability (K) and cerebral plasma volume (V{dollar}\sb{lcub}\rm p{rcub}){dollar} in human brain tumors in-vivo. In patient studies, Isovue 300 (iopamidol) was injected intravenously at a dosage of 1 ml/kg patient body weight. It was followed by serial head scanning of the tumor and arterial blood sampling to measure the contrast concentration in tumor and arterial plasma respectively. The leakage of iopamidol into the brain through the blood-brain barrier was modelled as an exchange process between two compartments, namely, the intravascular plasma space and the tissue interstitial space. Using this compartmental model and concentration measurement in tissue and blood plasma, quantitative estimates of K and V{dollar}\sb{lcub}\rm p{rcub}{dollar} were obtained with non-linear regression.;In a preliminary study of 12 patients, the average K and V{dollar}\sb{lcub}\rm p{rcub}{dollar} in brain tumors were found to be 0.0273 {dollar}\pm{dollar} 0.0060 ml/min/g and 0.068 {dollar}\pm{dollar} 0.11 ml/g respectively. These values were found to be significantly higher than those in the contralateral "normal" hemisphere (p {dollar}<{dollar} 0.05).;To increase the efficiency of the CT method in a clinical environment, an absorptiometry method was developed to measure contrast concentration in blood automatically. This method was based on the principle of single photon absorptiometry and was found to measure the arterial contrast concentration with a 5% uncertainty in patient studies.;Error analysis on the K estimate by the CT method was studied with sensitivity functions, computer simulations and covariance matrix formalism. The CT method was found to determine K in brain tumor with negligible bias and 5% uncertainty. In contrast, it determined K in normal brain with 14% bias and 73% uncertainty.;The CT method was used to study the effect of steroids on K in 10 patients. Each patient was studied twice: before and after 7 days of dexamethasone treatment of 16 mg/day orally. The results showed that K and V{dollar}\sb{lcub}\rm p{rcub}{dollar} in brain tumor decreased by 32% (p {dollar}<{dollar} 0.01) and 10% (p {dollar}<{dollar} 0.09) respectively after dexamethasone treatment. Functional images which map these parameters were also found to be more sensitive in detecting changes in K than ordinary contrast enhanced CT images.



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