(Developmental Center-Driven Research Project)

UC Davis: B Lin, R Raman, S Urayama, N Rahim, D Matthews, R Ramsamooj, R deVere White 

LLNL: SG Demos

Since its inception, CBST has been developing optical biopsy tools. Optical biopsy refers to the illumination of tissue by light of selected wavelengths and the subsequent spectroscopic analysis of light returning from the tissue to obtain a diagnosis of disease. Over the past year we have been exploring endoscope-compatible photonic methods and instrumentation for in vivo pathological assessment.

Light microscopy performed on fixed tissue sections is the current “gold standard” for viewing cells in tissues. The most important drawback of current pathology is that results cannot be obtained in real-time. Our goal is to develop techniques capable of providing real-time imaging of tissues microstructure accompanied by sufficient information for immediate in vivo pathological assessment of disease.

In the past year we have investigated a multimodal microscope design for real-time spectral imaging of intact tissues or organs using intrinsic optical signatures. Various samples from human and animal tissues have been imaged ex vivo, highlighting microstructures of interest while in vivo experiments have been performed in an animal model. Autofluorescence images are acquired under excitation from the UV to NIR using a set of compact lasers as well as an OPO tunable laser. Spectrally resolved light scattering imaging with polarization discrimination was used as a complimentary imaging method. Initial experiments have allowed clear visualization of microstructures such as cells and cell nuclei in unprocessed tissue specimens. Image contrast between tissue components depends on the excitation wavelength and tissue type. Results show that this imaging approach has the potential to provide information comparable to H&E staining in real time.

Design features for the current prototype include: 1) Conventional microscope using long working distance objectives to allow for off-axis illumination and imaging at any desirable wavelength; 2) Multi-wavelength excitation from an OPO laser or compact low power lasers to explore multiple intrinsic tissue chromophores; 3) Spectral and/or polarization filtering to enhance image contrast and remove out of focus image components; and 4) Optimized sensitivity for fast image acquisition.