The goal of this project is to develop functional magnetic resonance imaging (fMRI) tools to assist the diagnosis and treatment of human patients with a brain tumor or other operable pathology. The specific focus of this proposal is to produce a practical, clinic-ready suite of MR imaging methods, analyses and display tools to solve the number one impediment to routine use of fMRI for guiding brain surgery and radiation treatment: risk of brain damage due to the treatment itself. Currently, the primary clinical use of fMRI is to identify healthy brain tissue that might be damaged by surgery or radiation treatment and thereby cause an unintended neurological deficit such as partial blindness or paralysis. Neurosurgeons who use fMRI for this purpose have reported that it allows them to be more aggressive in removing the tumor because they don't have to guess where the healthy brain tissue is located. However, the success of using fMRI for this purpose depends on its ability to reliably distinguish between healthy brain tissue and diseased tissue that can be removed without causing a deficit. Herein, lies a critical problem. fMRI signals are not generated by the brain cells themselves but, rather, by localized changes in blood flow and oxygenation that are triggered when the brain cells become active as the patient performs a sensory, motor or cognitive task. The cascade of cellular events that link changes in brain cell activity to changes in blood flow is complex and can be disrupted by a brain tumor or other disease process. Disrupting this cascade causes neurovascular uncoupling (NVU) and results in a localized loss of the fMRI signal even though nearby brain cells are still functional. If NVU is not detected, healthy brain tissue can be mistaken for diseased tissue and inadvertently resected or irradiated. This can result in treatment-induced deficits such as partial loss of vision or limb movement. Fortunately, there are two promising methods that can be used to detect NVU but they have not been fully tested with patients nor have they been developed into tools that are ready for routine clinical use and distribution to the health care community. Consequently, the specific goal of this project is to address this need through a collaborative effort between imaging scientists and physicians at the Medical College of Wisconsin, Johns Hopkins University and Prism Clinical Imaging, Inc. This Phase 1 STTR project will address the feasibility of combining the two most promising methods, testing the combined method with a small number of patients, and developing prototype software for acquisition, analysis and visualization of NVU-related data. Successful completion of this project will lead to a subsequent Phase 2 project that will focus on testing a larger range of patients and pathologies and creating a commercial product ready for release to hospitals and clinics. It is anticipated that the proposed technology will have a significant impact on the use of fMRI for guiding brain surgery and on the acceptance of fMRI as standard of care for this purpose.

Public Health Relevance

The goal of this project is to develop functional magnetic resonance imaging (fMRI) tools to assist the diagnosis and treatment of human patients with a brain tumor or other operable pathology. The specific focus of this proposal is to produce a practical, clinic-ready suite of MR imaging methods, analyses and display tools to solve the number one impediment to routine use of fMRI for guiding brain surgery and radiation treatment: risk of brain damage due to the treatment itself. Currently, the primary clinical use of fMRI is to identify healthy brain tissue that might be damaged by surgery or radiation treatment and thereby cause an unintended neurological deficit such as partial blindness or paralysis. Neurosurgeons who use fMRI for this purpose have reported that it allows them to be more aggressive in removing the tumor because they don't have to guess where the healthy brain tissue is located. However, the success of using fMRI for this purpose depends on its ability to reliably distinguish between healthy brain tissue and diseased tissue that can be removed without causing a deficit. Herein, lies a critical problem. fMRI signals are not generated by the brain cells themselves but, rather, by localized changes in blood flow and oxygenation that are triggered when the brain cells become active as the patient performs a sensory, motor or cognitive task. The cascade of cellular events that link changes in brain cell activity to changes in blood flow is complex and can be disrupted by a brain tumor or other disease process. Disrupting this cascade causes 'neurovascular uncoupling' (NVU) and results in a localized loss of the fMRI signal even though nearby brain cells are still functional. If NVU is not detected, healthy brain tissue can be mistaken for diseased tissue and inadvertently resected or irradiated. This can result in treatment-induced deficits such as partial loss of vision or limb movement. Fortunately, there are two promising methods that can be used to detect NVU but they have not been fully tested with patients nor have they been developed into tools that are ready for routine clinical use and distribution to the health care community. Consequently, the specific goal of this project is to address this need through a collaborative effort between imaging scientists and physicians at the Medical College of Wisconsin, Johns Hopkins University and Prism Clinical Imaging, Inc. This Phase 1 STTR project will address the feasibility of combining the two most promising methods, testing the combined method with a small number of patients, and developing prototype software for acquisition, analysis and visualization of NVU-related data. Successful completion of this project will lead to a subsequent Phase 2 project that will focus on testing a larger range of patients and pathologies and creating a commercial product ready for release to hospitals and clinics. It is anticipated that the proposed technology will have a significant impact on the use of fMRI for guiding brain surgery and on the acceptance of fMRI as 'standard of care' for this purpose.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
5R42CA173976-04
Application #
9302687
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Narayanan, Deepa
Project Start
2013-07-08
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2019-06-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Prism Clinical Imaging Inc.
Department
Type
DUNS #
190899638
City
Elm Grove
State
WI
Country
United States
Zip Code
53122
Agarwal, Shruti; Hua, Jun; Sair, Haris I et al. (2018) Repeatability of language fMRI lateralization and localization metrics in brain tumor patients. Hum Brain Mapp 39:4733-4742
Agarwal, Shruti; Sair, Haris I; Pillai, Jay J (2017) Limitations of Resting-State Functional MR Imaging in the Setting of Focal Brain Lesions. Neuroimaging Clin N Am 27:645-661
Pak, Rebecca W; Hadjiabadi, Darian H; Senarathna, Janaka et al. (2017) Implications of neurovascular uncoupling in functional magnetic resonance imaging (fMRI) of brain tumors. J Cereb Blood Flow Metab 37:3475-3487
Agarwal, Shruti; Sair, Haris I; Pillai, Jay J (2017) The Resting-State Functional Magnetic Resonance Imaging Regional Homogeneity Metrics-Kendall's Coefficient of Concordance-Regional Homogeneity and Coherence-Regional Homogeneity-Are Valid Indicators of Tumor-Related Neurovascular Uncoupling. Brain Connect 7:228-235
Agarwal, Shruti; Lu, Hanzhang; Pillai, Jay J (2017) Value of Frequency Domain Resting-State Functional Magnetic Resonance Imaging Metrics Amplitude of Low-Frequency Fluctuation and Fractional Amplitude of Low-Frequency Fluctuation in the Assessment of Brain Tumor-Induced Neurovascular Uncoupling. Brain Connect 7:382-389
DeYoe, Edgar A; Ulmer, John L; Mueller, Wade M et al. (2015) Imaging of the Functional and Dysfunctional Visual System. Semin Ultrasound CT MR 36:234-48
DeYoe, Edgar A; Raut, Ryan V (2014) Visual mapping using blood oxygen level dependent functional magnetic resonance imaging. Neuroimaging Clin N Am 24:573-84