Liquid-crystal tunable filter spectral imaging for discrimination between normal and neoplastic tissues in the brain

Abstract

Current brain tumor localization methods demonstrate limited ability to discriminate between normal brain and infiltrating tumor margins, resulting in complete tumor resection in less than 20% of glioma patients. Combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain, but fiber-optic probe-based spectroscopy produces single-point diagnostic measurements. For optical biopsy to be clinically useful in tumor resection guidance, single-point spectroscopy systems must be extended to spectral imaging which acquires spectral information at every pixel within a two-dimensional field of view, yielding spatial and spectral tissue information for a comprehensive snapshot of tissue pathology during surgery.The primary goal behind each of the studies in this dissertation is to assess the capability of spectral imaging to rapidly and accurately demarcate tumor margins during surgery, requiring seamless integration of spectral imaging into the clinical environment, thorough investigation into the effects of the translation to non-contact imaging on measured fluorescence and diffuse reflectance lineshape, and high discrimination accuracy between normal tissue and tumor margins. With these mandates in mind, this dissertation describes the development and clinical testing of a combined fluorescence and diffuse reflectance spectral imaging system.In vitro optical property measurements from white matter, gray matter, and glioma tissues are correlated to diffuse reflectance spectral features from probe-based spectroscopy, are used to develop gelatin-based brain tissue phantoms for system testing, and provide practical soft-tissue optical property limits for investigations into the effects of non-contact spectral imaging geometry on measured lineshape. The liquid-crystal tunable filter spectral imaging system is thoroughly characterized in terms of traditional imaging parameters (linearity, field of view, resolution, sensitivity) and functionally tested in terms of image acquisition time and its capability to spectrally discriminate between brain tissues in vitro and in vivo. The effects of a shift in excitation-collection geometry from probe-based spectroscopy to spectral imaging on measured spectral lineshape are investigated as functions of optical properties, incident excitation and emission collection angles, and the distribution of source-detector separation distances in each system geometry. Ultimately, the capability of the spectral imaging system to intra-operatively differentiate glioma core and margin tissues from normal white and gray matter is quantitatively assessed in a retrospective clinical study. Spectral features in imaging fluorescence and diffuse reflectance spectra are correlated to histopathological diagnoses of human brain tissue biopsies to determine discrimination sensitivity and specificity for brain tumor margin demarcation and subsequent utility for surgical resection guidance.