Nonlinear Optical Imaging for Digital Pathology

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This project will develop a novel approach to improve histopathology, using multiple nonlinear light-tissue interactions that occur when intense but very short pulses of laser light (less than one billionth of a second) are used. These interactions provide novel mechanisms for image contrast in microscopy that complement and extend the information that are obtained using conventional microscopy with histological stains. Further, in order to make this technology maximally useful to clinical pathologists and biomedical researchers, the research team will develop a unique platform that will allow digital imaging of whole tissue slides, rather than imaging only small regions. Recently using an experimental small-field-of-view nonlinear microscopy, new information on lung cancer tissue biochemistry and ultrastructure has been obtained. The detailed structure of collagen (an important structural protein) has been found to be distinctly modified in tumor of lung tissue. The nucleoli within the cell nucleus have also been imaged, providing new insight into how they are altered with malignancy. These and other recent observations with nonlinear technique will be extended initially to several other cancer types (breast, prostate, gastrointestinal) to test if they are universal biomarkers of cancer. The nonlinear whole-slide scanner will be the enabling technology that will support development of new cancer diagnostics procedures, will stimulate other nonlinear optical biomarker development, and also will allow quick assessment of biological tissue structures without requiring staining. The scanner will generate digital images, and so the results can be directly integrated into electronic clinical records. The prototype instrument will be placed in a microscopy User Facility, and will be widely accessible to biomedical researchers, clinical pathologists, and researchers in other areas including dentistry, forensics, agriculture, geology, anthropology and bioengineering.