Quantitative Assessment of Angiogenesis By Perfusion MRI

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DESCRIPTION (provided by applicant): Broad long-term objectives: To develop methods of assessing angiogenesis in brain tumors using dynamic, contrast enhanced perfusion MRI (pMRI). Health-relatedness: The project will apply pMRI to the evaluation of brain tumors undergoing antioangiogenic and other chemotherapeutic treatments. However, the developed methods will also be useful in evaluating neoplastic lesions outside the brain and non-neoplastic lesions within it. Specific aims: 1) To investigate the hypothesis that pMRI measurements of cerebral blood volume (CBV) and vascular permeability correlate with histological assessments of vascularity and blood-brain barrier (BBB) breakdown respectively. 2) To determine whether pMRI can be used to grade brain tumors. 3) To investigate the hypothesis that pMRI can be used to monitor the efficacy of chemotherapeutic treatments. Research design: 1) Murine gliomas will be imaged with pMRI on a 7T animal imager. MRI measurements of CBV and vascular permeability will be correlated with histological assessments of vascular density and Evan's blue extravasation respectively. 2) CBV and vascular permeability will be measured in patients with histologically confirmed brain tumors of different grades to determine whether these measurements differentiate between them. 3) Serial pMRI measurements will be made on glioma patients enrolled in trials of new chemotherapeutic agents: thalidomide combined with carboplatin and the alkylating agents temodar and CPT-11. MRI measurements will be correlated with tumor size and clinical outcome to determine whether pMRI indications of angiogenesis predict tumor recurrence.