instrucfions): The goal of this project is to develop and test novel MR metabolic imaging approaches that will help to distinguish recurrent tumor from normal brain'and treatment effects in patients with glioblastoma (GBM). Characterizing temporal changes in tumor size and malignant potential is critically important for making fundamental decisions about patient care. The availability of imaging technologies that can provide more reliable metrics of tumor response to therapy and can identify progression at an early stage is critical for determining when to stop ineffective treatment and for selecting alternative strategies. We will integrate the multi-parametric imaging examination developed and validated in the current cycle of this P01 with novel H- 1 MR spectroscopic imaging techniques and new hyperpolarized C-13 metabolic imaging methods in order to develop improved mertics for evaluating the lesion. Linking in vivo imaging parameters with histological and genomic properties being studied in Project 2 and with information about therapeutic effects from Project 3 will provide important new strategies for selecting and evaluating novel therapeutics.
In Aim 1 we will develop and test a novel 3D H-1 MRSI sequence that provides automated prescription and significantly improved brain coverage for short echo (TE=20-35ms) spectral arrays. This will facilitate the estimation of in vivo levels of myo-lnositol in the same acquisition as choline, creatine and N-acetylasptate.
In Aim 2 we will utilize the unique experience and resources at UCSF to investigate the application of hyperpolarized C-13 MR metabolic imaging to patients with GBM. This exciting new technology has been shown in pre-clinical studies to differentiate tumor from normal tissue and provide a rapid assessment of response to therapy.
In Aim 3 we will use the techniques developed in Aims 1 and 2 in conjunction with image guided tissue sampling in order to determine wheytherthe following metabolic imaging parameters can improve upon the characterization of recurrent tumor and treatment effect: (i) the choline to N-acetylaspartate index, (ii) the ratio of myo-lnositol/choline and (ill) the ratio of hyperpolarized C-13 lactate/pyruvate.

Public Health Relevance

In this Project we will integrate novel metabolic and physiological imaging methods with tissue studies in order to determine which metabolic imaging parameters are the most effective in distinguishing recurrent tumor from treatment effects. This will have a major impact upon the clincial management of patients with GBM and upon the evaluation of novel therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA118816-07
Application #
8738070
Study Section
Special Emphasis Panel (ZCA1-RPRB-2)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
7
Fiscal Year
2014
Total Cost
$592,568
Indirect Cost
$216,984
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lupo, Janine M; Molinaro, Annette M; Essock-Burns, Emma et al. (2016) The effects of anti-angiogenic therapy on the formation of radiation-induced microbleeds in normal brain tissue of patients with glioma. Neuro Oncol 18:87-95
Mazor, Tali; Pankov, Aleksandr; Song, Jun S et al. (2016) Intratumoral Heterogeneity of the Epigenome. Cancer Cell 29:440-51
Park, Ilwoo; von Morze, Cornelius; Lupo, Janine M et al. (2016) Investigating tumor perfusion by hyperpolarized (13) C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts. Magn Reson Med :
Johannessen, Tor-Christian Aase; Mukherjee, Joydeep; Viswanath, Pavithra et al. (2016) Rapid Conversion of Mutant IDH1 from Driver to Passenger in a Model of Human Gliomagenesis. Mol Cancer Res 14:976-983
Cao, Peng; Shin, Peter J; Park, Ilwoo et al. (2016) Accelerated high-bandwidth MR spectroscopic imaging using compressed sensing. Magn Reson Med 76:369-79
Larson, Peder E Z; Han, Misung; Krug, Roland et al. (2016) Ultrashort echo time and zero echo time MRI at 7T. MAGMA 29:359-70
Radoul, Marina; Chaumeil, Myriam M; Eriksson, Pia et al. (2016) MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival. Mol Cancer Ther 15:1113-22
Bell, Robert J A; Rube, H Tomas; Xavier-Magalhães, Ana et al. (2016) Understanding TERT Promoter Mutations: A Common Path to Immortality. Mol Cancer Res 14:315-23
Nelson, Sarah J; Li, Yan; Lupo, Janine M et al. (2016) Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab. J Neurooncol 130:171-179
Cao, Peng; Zhang, Xiaoliang; Park, Ilwoo et al. (2015) (1) H-(13) C independently tuned radiofrequency surface coil applied for in vivo hyperpolarized MRI. Magn Reson Med :

Showing the most recent 10 out of 51 publications