A challenge in the surgical treatment of brain tumors is to preserve eloquent areas of brain function while maximizing extent of resection. To do so, current pre-operative and intra- operative brain mapping techniques require active patient participation, which limits their use in a significant number of patients (e.g. children). This limitation prohibits an optimal resection. There is an urgent need to develop brain mapping methodologies that can be used in all patients, can be performed both pre- and intra-operatively, and can be used in the setting of general anesthesia. New approaches based on resting state cortical physiology, such as functional connectivity MRI (fcMRI) and slow cortical potential mapping (SCPM), are emerging as techniques to identify motor and speech networks. The long-term goal of our research is to achieve more effective resections in a broader patient population with brain tumors near eloquent cortex by improving pre- and intra-operative mapping. The overall objective of this application is to define within patients with gliomas the correspondence between functional sites identified with resting state approaches to those areas identified by more established methods of pre-operative and intra-operative localization. The central hypothesis is that pre-operative fcMRI and intra-operative SCPM while under anesthesia will identify anatomic locations of eloquent cortex that are consistent with sites using the gold standard methods of pre-operative (task-based fMRI) and intra-operative (direct electrocortical stimulation, DECS) functional localization and with each other. The rationale that underlies this proposal is that this project wll provide a validated method of pre- and intra-operative brain mapping that can be done under anesthesia and in the absence of patient participation which will set the stage for more definitive clinical outcome studies in the future. We will test our central hypotheses with the following three specific aims: 1) Identify motor and language cortex in proximity to brain tumors using pre- operative resting state functional connectivity magnetic resonance imaging (fcMRI), 2) Identify motor and language cortex in proximity to brain tumors under anesthesia using intra-operative slow cortical potential mapping (SCPM), and 3) Define concordance between functional regions identified with fcMRI and SCPM in identifying DECS positive sites. We will implement these aims by enrolling 20 adults subjects with newly diagnosed primary gliomas that are to undergo surgical resection with intra-operative DECS. Using methods developed by our labs, each patient will get pre-operative fcfMRI and intra-operative SCPM and these findings will then be used to predict sites defined by current gold standard techniques. This project is innovative because these findings will provide a wholly new approach that is independent of patient state, does not require DECS, and can potentially be used to identify networks not currently mapped. Thus, this project is significant because resting-state mapping will obviate the need for patient participation/consciousness to successfully identify critical functional sites in the context of a brain tumor. In sum, such capabilities will make a larger patient population amenable to more effective resections and reduce individual and collective burden of brain tumors.

Public Health Relevance

The proposed research is relevant to public health because when brain tumors are diagnosed in critical parts of the brain, such as the motor or language areas, it is important for the neurosurgeon to know exactly where these areas are located in order to avoid damaging them during the tumor resection. Current methods for mapping these regions are limited to patients than can cooperate with the exam and cannot be performed in children or in patients that are confused or sedated. Consistent with the National Cancer Institute's mission, by developing brain mapping techniques that use resting state brain signals alone which do not require patient participation or consciousness, this project will greatly enhance the ability for more effective surgical treatments of brain tumors and be applicable to a broader patient population.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA159470-02
Application #
8338879
Study Section
Special Emphasis Panel (ZRG1-SBIB-W (56))
Program Officer
Henderson, Lori A
Project Start
2011-09-26
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$315,400
Indirect Cost
$107,900
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Freudenburg, Zachary V; Gaona, Charles M; Sharma, Mohit et al. (2014) Fast-scale network dynamics in human cortex have specific spectral covariance patterns. Proc Natl Acad Sci U S A 111:4602-7
Leuthardt, Eric C; Roland, Jarod; Breshears, Jonathan et al. (2013) Listening to the brain: new techniques in intraoperative brain mapping. Neurosurgery 60 Suppl 1:64-9
Hacker, Carl D; Laumann, Timothy O; Szrama, Nicholas P et al. (2013) Resting state network estimation in individual subjects. Neuroimage 82:616-33