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.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
Program Officer
Krosnick, Steven
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State University New York Stony Brook
Biomedical Engineering
Schools of Engineering
Stony Brook
United States
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Chen, Ye; Liu, Jonathan T C (2015) Characterizing the beam steering and distortion of Gaussian and Bessel beams focused in tissues with microscopic heterogeneities. Biomed Opt Express 6:1318-30
Meza, Daphne; Wang, Danni; Wang, Yu et al. (2015) Comparing high-resolution microscopy techniques for potential intraoperative use in guiding low-grade glioma resections. Lasers Surg Med 47:289-95
Leigh, Steven; Chen, Ye; Liu, Jonathan (2015) Modulated-alignment dual-axis (MAD) confocal microscopy optimized for speed and contrast. IEEE Trans Biomed Eng :
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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
Wang, D; Chen, Y; Wang, Y et al. (2013) Comparison of line-scanned and point-scanned dual-axis confocal microscope performance. Opt Lett 38:5280-3
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. (2013) Real-time pathology through in vivo microscopy. Stud Health Technol Inform 185:235-64
Chen, Ye; Liu, Jonathan T C (2013) Optimizing the performance of dual-axis confocal microscopes via Monte-Carlo scattering simulations and diffraction theory. J Biomed Opt 18:066006

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