The overall goal of the new P01 is to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma. This will be achieved by characterizing the evolution of changes in imaging, genetic and epigenetic profiles from the time of initial presentation until presumed tumor progression. The information obtained will be applied to determine whether it is possible to tailor treatment strategies to individual patients and will be used in combination with hyperpolarized C-13 metabolic imaging to inform on the early response to therapeutic agents. The results of these studies will address critical challenges in the field of Neuro-Oncology and have the potential to make a significant impact upon the management of patients with brain tumors. Three highly integrated and synergistic projects are planned: Project 1: Improved management of GBM by integrated imaging and tissue analysis. Project 2: Image guided genome-epigenome analysis of tumor heterogeneity and evolution and Project 3: Hyperpolarized carbon 13 MRSI monitoring of pyruvate metabolism to assess drug action. The overall specific aims of the P01 are: 1) To accurately define tumor burden in the post treated setting. Projects 1 and 3 will assess the role of novel imaging techniques to assess tumor burden. 2) To characterize intratumoral heterogeneity (imaging parameters, histologic characteristics, genetic/epigenetic features) and the effect on treatment response, tumor evolution and clinical outcome. Projects 1 and 2 will be integrated to accomplish this aim. 3) To assess early response to therapy to assist with treatment decisions. Projects 1 and 3 will accomplish this aim through the clinical development and application of hyperpolarized C-13 imaging in conjunction with physiological and metabolic imaging techniques. Three shared resources (Administrative and Clinical Services Core, Biospecimen and Biostatistics Core and the Imaging Core) will provide key services that are essential for the Projects to accomplish their aims.
This P01 will address key challenges related to the accurate determination of tumor burden in the post treated setting, to the evaluation of tumor heterogeneity, which hampers the selection of appropriate therapies, and to the early assessment of response to therapy in patients with GBM. This is critical for optimizing clinical care and will have a significant impact on the development of new treatment strategies.
|Ohba, Shigeo; Mukherjee, Joydeep; See, Wendy L et al. (2014) Mutant IDH1-driven cellular transformation increases RAD51-mediated homologous recombination and temozolomide resistance. Cancer Res 74:4836-44|
|Park, Ilwoo; Larson, Peder E Z; Tropp, James L et al. (2014) Dynamic hyperpolarized carbon-13 MR metabolic imaging of nonhuman primate brain. Magn Reson Med 71:19-25|
|Elkhaled, Adam; Jalbert, Llewellyn; Constantin, Alexandra et al. (2014) Characterization of metabolites in infiltrating gliomas using ex vivo ¹H high-resolution magic angle spinning spectroscopy. NMR Biomed 27:578-93|
|Ahluwalia, Manmeet S; Chang, Susan M (2014) Medical therapy of gliomas. J Neurooncol 119:503-12|
|Lupo, Janine M; Nelson, Sarah J (2014) Advanced magnetic resonance imaging methods for planning and monitoring radiation therapy in patients with high-grade glioma. Semin Radiat Oncol 24:248-58|
|Park, Ilwoo; Mukherjee, Joydeep; Ito, Motokazu et al. (2014) Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells. Cancer Res 74:7115-24|
|Rosenbluth, Kathryn Hammond; Gimenez, Francisco; Kells, Adrian P et al. (2013) Automated segmentation tool for brain infusions. PLoS One 8:e64452|
|Rosenbluth, Kathryn H; Martin, Alastair J; Mittermeyer, Stephan et al. (2013) Rapid inverse planning for pressure-driven drug infusions in the brain. PLoS One 8:e56397|
|Ozhinsky, Eugene; Vigneron, Daniel B; Chang, Susan M et al. (2013) Automated prescription of oblique brain 3D magnetic resonance spectroscopic imaging. Magn Reson Med 69:920-30|
|Constantin, Alexandra; Elkhaled, Adam; Jalbert, Llewellyn et al. (2012) Identifying malignant transformations in recurrent low grade gliomas using high resolution magic angle spinning spectroscopy. Artif Intell Med 55:61-70|
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