In brain cancers such as gliomas, aggressive removal of the solid tumor through surgery is associated with improved overall survival. In fact, i has been shown that at least 78% of the tumor has to be removed to make a meaningful difference in the patient's survival. Current techniques for tumor removal are limited in their ability to safely and accurately identify tumor versus non-tumor tissues in real-time. The objective of this work is to develop, test, and validate the ability of optical coherence tomography (OCT) imaging to distinguish tumor tissues from non-tumor tissues with very high precision. We will use a high speed/resolution swept-source OCT imaging system to achieve high accuracy. This distinction of tumor tissues is especially important at the boundaries of the tumor or transitional zones, which are difficult to identify intra- operatively with current techniques. To achieve the goal of developing, testing and validating our new technique, we propose 2 specific aims for this study: 1) using high-speed and high-resolution OCT, we will study tissue characteristics of the ex vivo tumor and non-tumor brain tissues obtained from high grade glioma patients. Diagnostic sensitivity and specificity of the OCT methods will be computed. 2) We will test the performance of the real-time OCT handheld probe within an intraoperative setting by surgical debulking of implanted brain tumors in small animal models. By the end of this study, we will have demonstrated the ability of real-time, high-resolution OCT to detect transitional tumor margins between tissues. The collective results of this study will potentially maximize the extent of resection of infiltrative tumors and thereby increasing overall survival of patients. If this study is successful, the OCT technique can also be applied to a variety of other central nervous system (CNS) tumors including low grade gliomas, pituitary tumors, pediatric medulloblastoma, spinal cord tumors and certain metastatic brain cancers when tumor margins are not well defined. In summary, this study has the potential to challenge current practices in neurosurgery and lead to widespread implementation of the OCT device.

Public Health Relevance

Glioblastoma is the most common brain cancer and is not curable with an average survival of 14 months. The ultimate goal of neurosurgery is to maximize the extent of cancer resection without compromising brain function, since maximal resection is positively associated with improved patient survival;nevertheless, current techniques such as intra-operative MRI, ultrasound and cortical mapping are suboptimal in identifying infiltrative glioma margins between tumor and non-tumor tissue. Our proposed study uses a high-speed/resolution hand-held optical coherence tomography (OCT) imaging probe to pinpoint and identify tumor margins in real-time, with the goal of achieving over 90% sensitivity and specificity.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Special Emphasis Panel (ZRG1)
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Damico, Mark W
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Johns Hopkins University
Biomedical Engineering
Schools of Medicine
United States
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Yuan, Wu; Kut, Carmen; Liang, Wenxuan et al. (2017) Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection. Sci Rep 7:44909
Kut, Carmen; Grossman, Stuart A; Blakeley, Jaishri (2015) How critical is the blood-brain barrier to the development of neurotherapeutics? JAMA Neurol 72:381-2
Kut, Carmen; Chaichana, Kaisorn L; Xi, Jiefeng et al. (2015) Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography. Sci Transl Med 7:292ra100
Kut, Carmen; Janson Redmond, Kristin (2014) New considerations in radiation treatment planning for brain tumors: neural progenitor cell-containing niches. Semin Radiat Oncol 24:265-72