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.

National Institute of Health (NIH)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Zhang, Huiming
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Vanderbilt University Medical Center
Schools of Medicine
United States
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Semmineh, Natenael B; Xu, Junzhong; Skinner, Jack T et al. (2015) Assessing tumor cytoarchitecture using multiecho DSC-MRI derived measures of the transverse relaxivity at tracer equilibrium (TRATE). Magn Reson Med 74:772-84
Semmineh, Natenael B; Xu, Junzhong; Boxerman, Jerrold L et al. (2014) An efficient computational approach to characterize DSC-MRI signals arising from three-dimensional heterogeneous tissue structures. PLoS One 9:e84764
Skinner, Jack T; Robison, Ryan K; Elder, Christopher P et al. (2014) Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain. Magn Reson Imaging 32:1171-80
Stokes, Ashley M; Skinner, Jack T; Quarles, C Chad (2014) Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging. Magn Reson Imaging 32:1181-90
Barnes, Stephanie L; Quarles, C Chad; Yankeelov, Thomas E (2014) Modeling the effect of intra-voxel diffusion of contrast agent on the quantitative analysis of dynamic contrast enhanced magnetic resonance imaging. PLoS One 9:e108726