This preclinical project combines imaging technology development with biomarker discovery for functional image guidance during resection of meduloblastoma (MB), the most common pediatric brain tumor. A novel imaging technology, the dual-axis confocal (DAC) microscope, will be developed to image fluorescent probes that target MB biomarkers. First, a tabletop DAC will be used, along with targeted probes, to image a spontaneous mouse tumor model of MB. A quantitative ratiometric-imaging method will be employed to improve tumor-to-normal image contrast, which will also be maximized by optimizing parameters such as imaging depth, probe concentration, and the procedure for rinse removal of unbound probe. A miniature DAC, which incorporates a 2-mm diameter gradient index "needle" lens, will be developed to guide MB debulking surgeries in mice. Improved resection will be demonstrated by quantifying residual tumor mass, time-to-relapse, and by monitoring overall survival. These technologies and methods will enable more complete and accurate resection of MB in the brain, and will thereby improve patient outcomes, by allowing surgeons to visualize tumor margins with cellular accuracy and molecular specificity.

Public Health Relevance

This project will develop a microscopic imaging tool, along with targeted contrast agents, to improve the ability of surgeons to remove brain tumors. Since the extent of tumor removal correlates with patient outcomes, and accurate resections are desired to prevent neurological damage, the potential impact on public health is far reaching.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Transition Award (R00)
Project #
5R00EB008557-05
Application #
8305428
Study Section
Special Emphasis Panel (NSS)
Program Officer
Krosnick, Steven
Project Start
2009-08-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$236,766
Indirect Cost
$76,154
Name
State University New York Stony Brook
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Leigh, Steven Y; Chen, Ye; Liu, Jonathan T C (2014) Modulated-alignment dual-axis (MAD) confocal microscopy for deep optical sectioning in tissues. Biomed Opt Express 5:1709-20
Liu, Jonathan T C; Meza, Daphne; Sanai, Nader (2014) Trends in fluorescence image-guided surgery for gliomas. Neurosurgery 75:61-71
Liu, Jonathan T C; Loewke, Nathan O; Mandella, Michael J et al. (2013) Real-time pathology through in vivo microscopy. Stud Health Technol Inform 185:235-64
Leigh, Steven Y; Som, Madhura; Liu, Jonathan T C (2013) Method for assessing the reliability of molecular diagnostics based on multiplexed SERS-coded nanoparticles. PLoS One 8:e62084
Liu, Jonathan T C; Loewke, Nathan O; Mandella, Michael J et al. (2011) Point-of-care pathology with miniature microscopes. Anal Cell Pathol (Amst) 34:81-98