The overall goals of the proposed research are to develop dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) methods for the simultaneous assessment of tumor perfusion, permeability and cellularity in cerebral and non-cerebral tumors and to evaluate their role as potential surrogate biomarkers of treatment response. As the biophysical basis of DSC-MRI signals acquired in the presence of contrast agent extravasation is more comprehensively characterized it is evident that they reflect additional underlying biological features such as the vascular integrity and/or cellularity, not unlike those interrogated with dynamic contrast enhanced (DCE) MRI and diffusion weighted (DW)-MRI. To this end we propose to develop a DSC- MRI method that enables the simultaneous acquisition of reliable blood flow and blood volume measures, DCE-MRI data and a new imaging metric, the extravascular susceptibility calibration factor, which we propose reflects cellular features such as density and/or spacing. To characterize and validate the proposed method we will compare DSC-MRI, DCE-MRI and quantitative autoradiography derived measures of perfusion (Aim 1) and permeability (Aim 2) in orthotopic brain and breast tumor models. The DSC-MRI based tumor cellularity metric will be characterized in cellular phantoms and tumor tissue, compared with DW-MRI and validated using histology (Aim 3). Finally, given the pre-clinical and clinical success of DCE-MRI and DW-MRI to assess treatment response, we will compare their sensitivity to that of the proposed imaging metrics to asses treatment induced changes in tumor vascular and cellular status (Aim 4). Significance: The validation of the proposed methods would enable the simultaneous acquisition of parameters reflecting perfusion, permeability and cellularity thereby reducing total MRI scan time and contrast agent dose. Such an approach could greatly enhance clinical care by providing an efficient and more comprehensive assessment of tumor treatment response and enabling the application of DSC-MRI methods to non-cerebral tumors.

Public Health Relevance

The proposed research focuses on the development of magnetic resonance imaging methods that provide a more efficient and complete assessment of a tumor's response to treatment. Such methods could decrease health care costs, contrast agent dose and improve the way treatments are planned and monitored.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA158079-05
Application #
8895276
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zhang, Huiming
Project Start
2011-09-16
Project End
2015-12-03
Budget Start
2015-08-01
Budget End
2015-12-03
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37240
Woodall, Ryan T; Barnes, Stephanie L; Hormuth 2nd, David A et al. (2017) The effects of intravoxel contrast agent diffusion on the analysis of DCE-MRI data in realistic tissue domains. Magn Reson Med :
Bell, L C; Does, M D; Stokes, A M et al. (2017) Optimization of DSC MRI Echo Times for CBV Measurements Using Error Analysis in a Pilot Study of High-Grade Gliomas. AJNR Am J Neuroradiol 38:1710-1715
Sorace, Anna G; Syed, Anum K; Barnes, Stephanie L et al. (2017) Quantitative [18F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer. Mol Imaging Biol 19:130-137
Semmineh, Natenael B; Stokes, Ashley M; Bell, Laura C et al. (2017) A Population-Based Digital Reference Object (DRO) for Optimizing Dynamic Susceptibility Contrast (DSC)-MRI Methods for Clinical Trials. Tomography 3:41-49
Bell, Laura C; Hu, Leland S; Stokes, Ashley M et al. (2017) Characterizing the Influence of Preload Dosing on Percent Signal Recovery (PSR) and Cerebral Blood Volume (CBV) Measurements in a Patient Population With High-Grade Glioma Using Dynamic Susceptibility Contrast MRI. Tomography 3:89-95
Hu, Leland S; Ning, Shuluo; Eschbacher, Jennifer M et al. (2017) Radiogenomics to characterize regional genetic heterogeneity in glioblastoma. Neuro Oncol 19:128-137
Stokes, Ashley M; Hart, Charles P; Quarles, C Chad (2016) Hypoxia Imaging With PET Correlates With Antitumor Activity of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) in Rodent Glioma Models. Tomography 2:229-237
Stokes, Ashley M; Skinner, Jack T; Yankeelov, Thomas et al. (2016) Assessment of a simplified spin and gradient echo (sSAGE) approach for human brain tumor perfusion imaging. Magn Reson Imaging 34:1248-1255
Newton, A T; Pruthi, S; Stokes, A M et al. (2016) Improving Perfusion Measurement in DSC-MR Imaging with Multiecho Information for Arterial Input Function Determination. AJNR Am J Neuroradiol 37:1237-43
Stokes, Ashley M; Quarles, C Chad (2016) A simplified spin and gradient echo approach for brain tumor perfusion imaging. Magn Reson Med 75:356-62

Showing the most recent 10 out of 19 publications