Cancer ranks second as the cause of death from disease in the United States. Brain tumors rank second as the cause of cancer-related deaths in children and adults younger than 34 years old, and they affect adults of all ages. Primary malignant brain tumors are associated with the third highest cancer-related mortality rate and a disproportionate level of disability and morbidity. Accurate diagnosis and grading of brain tumors is critical to determining prognosis and therapy. The health related focus of this proposal is to reduce morbidity and mortality rates for patients with brain tumors through the development of a comprehensive magnetic resonance (MR) imaging (MRI)-based grading system that assesses tumor behavior and prognosis. We propose that comprehensive, quantitative, structural and non-anatomic MRI and proton MR spectroscopy (1H MRS) can provide surrogate markers of tumor malignancy permitting accurate preoperative grading of brain tumors, and potentially can offer independent prognostic information above and beyond the histopathologic phenotype. Our central hypothesis is that the malignant biologic behavior of primary brain tumors and the early stages of an aggressive growth phase are related to tumor angiogenesis, which can be measured quantitatively and non-invasively by using perfusion MRI (pMRI) methods. The overarching goal of this proposal is to apply a comprehensive, quantitative MRI method that will augment current methods of diagnosis and tumor grading, provide earlier evidence of treatment failure, identify surrogate markers of survival outcome, and aid in the development of novel therapies. The applicant's immediate goal is to acquire the knowledge and skills required to become an independent clinician-investigator focused on patient-oriented research through phased and well-designed, multidisciplinary, didactic training in the basic biology of brain tumors, in biostatistics and clinical study design, and in methods of optimizing pMRI and multidimensional 1H MRS.
Specific Aim 1 is to develop an imaging-based system for grading gliomas by using comprehensive MRI methods and to identify those MR variables that best predict tumor malignancy.
Specific Aim 2 is to validate MRI measurements of tumor angiogenesis and vascular permeability with histologic markers by directly correlating imaging and histologic results from biopsy samples obtained from the same anatomic location.
Specific Aim 3 is to predict treatment response and progression-free survival by using changes in perfusion and metabolic MRI variables before and after therapy in patients with newly diagnosed malignant glioma undergoing external-beam radiation therapy while participating in a clinical trial of adjuvant chemotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS045013-05
Application #
7224789
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fountain, Jane W
Project Start
2003-08-01
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2009-04-30
Support Year
5
Fiscal Year
2007
Total Cost
$161,406
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Barajas Jr, R F; Phillips, J J; Vandenberg, S R et al. (2015) Pro-angiogenic cellular and genomic expression patterns within glioblastoma influences dynamic susceptibility weighted perfusion MRI. Clin Radiol 70:1087-95
Barajas Jr, R F; Hess, C P; Phillips, J J et al. (2013) Super-resolution track density imaging of glioblastoma: histopathologic correlation. AJNR Am J Neuroradiol 34:1319-25
Barajas Jr, Ramon F; Perry, Arie; Sughrue, Michael et al. (2012) Intracranial subdural osteoma: a rare benign tumor that can be differentiated from other calcified intracranial lesions utilizing MR imaging. J Neuroradiol 39:263-6
Barajas Jr, R F; Rubenstein, J L; Chang, J S et al. (2010) Diffusion-weighted MR imaging derived apparent diffusion coefficient is predictive of clinical outcome in primary central nervous system lymphoma. AJNR Am J Neuroradiol 31:60-6
Barajas Jr, Ramon F; Hodgson, J Graeme; Chang, Jamie S et al. (2010) Glioblastoma multiforme regional genetic and cellular expression patterns: influence on anatomic and physiologic MR imaging. Radiology 254:564-76
Barajas, R F; Chang, J S; Sneed, P K et al. (2009) Distinguishing recurrent intra-axial metastatic tumor from radiation necrosis following gamma knife radiosurgery using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. AJNR Am J Neuroradiol 30:367-72
Barajas Jr, Ramon F; Chang, Jamie S; Segal, Mark R et al. (2009) Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology 253:486-96
Diehn, Maximilian; Nardini, Christine; Wang, David S et al. (2008) Identification of noninvasive imaging surrogates for brain tumor gene-expression modules. Proc Natl Acad Sci U S A 105:5213-8
Cha, S; Lupo, J M; Chen, M-H et al. (2007) Differentiation of glioblastoma multiforme and single brain metastasis by peak height and percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. AJNR Am J Neuroradiol 28:1078-84
Smith, Justin S; Lin, Henry; Mayo, Mary Catherine et al. (2006) Diffusion-weighted MR imaging abnormalities in pediatric patients with surgically-treated intracranial mass lesions. J Neurooncol 79:203-9

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