Towards in-vivo label-free detection of brain tumor margins with epi-illumination tomographic quantitative phase imaging

• Type of Material: Article
• Authors: Paloma C Costa, Georgia Institute of Technology; Zhe Guang, Georgia Institute of Technology; Patrick Ledwig, Georgia Institute of Technology; Zhaobbin Zhang, Emory University; Stewart Neill, Emory University; Jeffrey Olson, Emory University; Francisco Robles, Emory University
• Language: English
• Date: 2021-03-01
• Publisher: OPTICAL SOC AMER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1364/BOE.416731
• Title of Journal or Parent Work: BIOMEDICAL OPTICS EXPRESS
• Volume: 12
• Issue: 3
• Start Page: 1621
• End Page: 1634
• Grant/Funding Information: Burroughs Wellcome Fund10.13039/100000861 (1014540); Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M); National Cancer Institute10.13039/100000054 (R21CA223853); National Institute of Neurological Disorders and Stroke10.13039/100000065 (R21NS117067); National Science Foundation10.13039/100000001 (CAREER 1752011); Georgia Institute of Technology10.13039/100006778.
• Keywords: Physical Sciences; Radiology, Nuclear Medicine & Medical Imaging; ACID; Biochemical Research Methods; Optics; Biochemistry & Molecular Biology; TISSUE; GUIDED SURGERY; GRADE GLIOMAS; IMPACT; CANCER; MICROSCOPY; Science & Technology; Life Sciences & Biomedicine; EXTENT; RESECTION; SURVIVAL
• Research Categories: Engineering, Electronics and Electrical; Health Sciences, Pathology; Health Sciences, Oncology

Abstract

Brain tumor surgery involves a delicate balance between maximizing the extent of tumor resection while minimizing damage to healthy brain tissue that is vital for neurological function. However, differentiating between tumor, particularly infiltrative disease, and healthy brain in-vivo remains a significant clinical challenge. Here we demonstrate that quantitative oblique back illumination microscopy (qOBM)—a novel label-free optical imaging technique that achieves tomographic quantitative phase imaging in thick scattering samples—clearly differentiates between healthy brain tissue and tumor, including infiltrative disease. Data from a bulk and infiltrative brain tumor animal model show that qOBM enables quantitative phase imaging of thick fresh brain tissues with remarkable cellular and subcellular detail that closely resembles histopathology using hematoxylin and eosin (H&E) stained fixed tissue sections, the gold standard for cancer detection. Quantitative biophysical features are also extracted from qOBM which yield robust surrogate biomarkers of disease that enable (1) automated tumor and margin detection with high sensitivity and specificity and (2) facile visualization of tumor regions. Finally, we develop a low-cost, flexible, fiber-based handheld qOBM device which brings this technology one step closer to in-vivo clinical use. This work has significant implications for guiding neurosurgery by paving the way for a tool that delivers real-time, label-free, in-vivo brain tumor margin detection.