Integrated Time-Resolved Fluorescence and Diffuse Reflectance Spectroscopy Instrument for Intraoperative Detection of Brain Tumor Margin

Time-resolved fluorescence (TRF) and diffuse reflectance (DR) spectroscopy are two optical biopsy modalities that have been studied in tumor diagnosis. Combination of TRF and DR spectroscopy allows us to obtain more features such as fluorescence intensity, lifetime, and optical properties; thus, potentially improving the tissue diagnostic accuracy. In this paper, an integrated TRF-DR spectroscopy instrument was developed to acquire TRF spectra as well as spatially resolved diffuse reflectance spectra in sequence for intraoperative detection of brain tumor margin. The performance of TRF-DR spectroscopy instrumentation was calibrated and evaluated using endogenous biomolecules, tissue phantoms, and ex vivo brain tumor specimens. The results demonstrated that the TRF-DR system is capable to retrieve the fluorescence and optical properties accurately.

I. Introduction

Brain and central nervous system (CNS) tumors were responsible for nearly 23 380 new cases and 14 320 deaths in the United States in 2014 [1]. Glioblastoma (or GBM) is a very aggressive type of tumor and account for 80% of malignant primary brain tumors [2]. Surgery is the most commonly prescribed treatment for malignant gliomas. The prognosis of patients is directly correlated to the completeness of tumor removal during surgery [3]. Due to the infiltrative characteristics and morphological similarity to normal brain tissue, complete resection of malignant gliomas is difficult to achieve. The current “gold standard” for the diagnosis of tissue status in neurosurgery is excisional biopsy [4], which is time-consuming and unable to provide real-time diagnosis. In addition, for brain tissue biopsy, only limited samples can be resected to avoid damages to the normal brain, which may lead to sampling error.