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Development of Medical Mutiphoton Microscopic Endoscopy
Watt W. Webb (PI) Professor of Applied and Engineering Physics, Cornell University.
Weill Medical College, New York, NY:
Fahey, Thomas J., Co-I, Associate Professor of Surgery
Maxfield, Frederick R., Co-I, Chair, Department of Biochemistry
Milsom, Jeffrey W., Co-I, Professor of Surgery
Pochapin, Mark B., Co-I, Chief, Division of Gastrointestinal Endoscopy
Scherr, Douglas S., Co-I, Assistant Professor of Urology
Tewari, Ashutosh K., Co-I, Associate Professor of Urology
Funding: NIH/NIBIB R01-EB006736 Development of Medical Multiphoton Microscopic Endoscopy (6/07-3/12)

Autofluorescence and second harmonic generation in tissue imaged by multiphoton microscopy (MPM) may enable important biomedical use of the capabilities of MPM for in vivo detection and diagnostic recognition of disease. MPM Endoscopy will utilize the MPM imaging capabilities to translate this capability into the clinic. The first aim is development of foundation data comparing MPM images of fresh biopsies with collaborating pathologists’ histology and clinical diagnoses, leading to production of an “atlas” of diagnostic MPM images for eventual dissemination. To accomplish the translation of MPM tissue imaging capabilities from the laboratory to medical applications via endoscopy, a representative cadre of physicians and surgeons at Weill Medical has been assembled to test and evaluate this capability. Simultaneously, another aim is the development of miniaturized, reliable MPM endoscopic apparatuses compatible with the diverse geometries required for various organs. To accomplish this objective, innovative research by our key personnel with established expertise in ultrafast optics and nanostructure fabrication is invoked to design, fabricate and test potential systems. Finally, technology transfer to commercial manufacturers to provide medical instrument availability is required. The overall objective of this Bioengineering Research Partnership is creation of significant advances in the functional effectiveness of medical endoscopy, enabling real-time, micro-imaging of the intrinsic diagnostic properties of tissue in vivo.

The key feature of MPM imaging that enables this Medical Endoscopic Microscopy development is the discovery and measurements of the intrinsic fluorescence and Second Harmonic Generation (SHG) by various living tissue components. This feature was explored and developed by DRBIO and collaborations and is expected to continue in close collaboration with Weill Medical. It depends critically on Resource personnel and equipment and on collaborations with faculty of Cornell’s College of Veterinary Medicine.   An MPM system with optimized autofluorescence and SHG detection has been installed at Weill Medical (Figure 1). This system was funded by Weill Medical, built by DRBIO and is being used to image fresh biopsy material. The new Multiphoton Endoscopy center also has initial endoscope designs under construction. A first MPM Endoscope design has been created by Professors Chris Xu and Watt Webb to address the selected initial applications in urological surgery for treatment of cancers within the bladder and prostate. This 5 mm diameter design includes three coaxial optical systems, MPM laser scanning illumination of an in-tissue focal volume, an efficient fluorescence collection pathway, and a low magnification back-scattering microscope to guide the selection of sites for MPM microscopic imagery.  It is planned to arrange testing of the initial rigid endoscopes in medium size animal models with the help of the Cornell College of Veterinary Medicine.

The essential biomedical challenge of the ongoing developments of MPM Endoscopy for Medical applications is to establish the correspondence between MPM images of diseased tissues and the fixed Hematoxylin and Eosin (H&E) absorption tissue slices customarily used by pathologists. Using the system constructed by DRBIO at Weill, we plan to create an “Atlas” of human tissue images, initially of biopsies comparing both MPM and standard H&E images. Pilot tests of this strategy have been based on work in the Resource; however, it is anticipated that the outgrowth of this strategy will become an important research area at Weill Medical. The continuing pursuit of these objectives will also depend heavily on DRBIO for its experimental base and intellectual collaboration. Clearly essential to this project are ITE-MPM characterization studies in project III as well as instrument development in core R&D project I.  Image acquisition hardware and software for the new endoscope will be developed by DRBIO.

 

 

 



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