A microsphere-fiber probe used for spectroscopic analysis of material samples is presented. The monolithic structure is formed by melting the end of a section of optical fiber forming a bead at the distal end of the fiber. Light guided through the fiber and emerges from the sphere focusing to a point beyond the surface. Raman scattering is used to demonstrate the efficacy of the probe, which operates in a bidirectional manner efficiently collecting the scattered light, re-imaging it back into the waveguide, and transmitting it to a spectrometer for dispersion. The probe demonstrates an order of magnitude improvement over the spatial resolution conventional fiber probes. This improvement in spatial resolution and corresponding collection efficiency will aid in critical analyses such as cancer margin detection and material characterization.
The goal of oncologic resection is to eradicate all malignant cells, while minimizing loss of surrounding normal tissue (or so-called “negative margins”). Failure to achieve negative margins constitutes an adverse prognostic factor, which has a significant impact on patient’s quality of life and cancer recurrence. Significant barriers to obtaining a negative margins resection in real time exist and novel imaging platforms are needed which can be utilized during robotic tumor resection. In order to develop a novel endoscopic imaging platform for head and neck surgery: We propose to combine functional measurement of molecular tissue constituents with lifetime molecular imaging of metabolism. This will couple traditional stereo laparoscopic images with Single Snapshot of Optical Properties (SSOP)/ Fluorescence Lifetime Imaging FLI NIR, and Phasor computational lifetime imaging technology (PHASOR) simultaneously into a dual channel robotic endoscope and tested via optical phantoms having realistic tissue properties. This platform will use a variety of techniques including to image endogenous molecular constituents, namely oxyhemoglobin, deoxyhemoglobin, water, NADH, and NADPH providing a quantitative measurement of physiological parameters. Such information can be used to identify healthy and diseased tissue intraoperatively, providing a unique opportunity to delineate surgical margins in real-time. Pre-clinical mice models bearing tumor xenografts will be imaged using the tri-modal system to record: visible light image, hemodynamics parameters and metabolic status and test the feasibility of the identification of tumor margins in real time.
Optical probes to identify tumor margins in vivo would greatly reduce the time, effort and complexity in the surgical removal of malignant tissue in head and neck cancers. Current approaches involve visual microscopy of stained tissue samples to determine cancer margins, which results in the excision of excess of tissue to assure complete removal of the cancer. Such surgical procedures and follow-on chemotherapy can adversely affect the patient’s recovery and subsequent quality of life. In order to reduce the complexity of the process and minimize adverse effects on the patient, we investigate ex vivo tissue samples (stained and unstained) using digital holographic microscopy in conjunction with spectroscopic analyses (reflectance and transmission spectroscopy) in order to determine label-free, optically identifiable characteristic features that may ultimately be used for in vivo processing of cancerous tissues. The tissue samples studied were squamous cell carcinomas and associated controls from patients of varying age, gender and race. Holographic microscopic imaging scans across both cancerous and non-cancerous tissue samples yielded amplitude and phase reconstructions that were correlated with spectral signatures. Though the holographic reconstructions and measured spectra indicate variations even among the same class of tissue, preliminary results indicate the existence of some discriminating features. Further analyses are presently underway to further this work and extract additional information from the imaging and spectral data that may prove useful for in vivo surgical identification.
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