The confocal miniprobe (Cell-viZio-GI?) used in Specific Aim 2 provides horizontal cross-sectional images up to 100 (im tissue penetration depth. This distance is insufficient to assess for the presence of neoplastic invasion and micrometastases below the muscularis mucosa (Fig 3b), which is needed to accurately stage the progression of cancer. We have achieved vertical cross-sectional images with 500 ^m tissue penetration depth ex vivo using the novel dual axes confocal architecture (Fig 8b). This orientation is preferred :for pathological evaluation because it reveals the natural growth and proliferation of tissue micro-structures. Furthermore, we have developed a 5 mm diameter (endoscope compatible) dual axes prototype that achieves high speed scanning in the horizontal (xy-) plane using a MEMS (micro-electro-mechanical sytems) mirror. In order to achieve vertical cross-sections, we need to develop an axial (z-) scanner that performs with sufficient speed for in vivo imaging. MEMS actuators have been developed previously for a number of applications, including computer hard drives,82'83 aviation fluid control systems,84 and optical fiber manipulators.85 These designs are based on electrostatic, thermal, or electromagnetic principles. Howev.er, each of these approaches have limitation in either the amount of force that can be generated or by the size and power required to move the scanhead over the desired range of motion. Pneumatic actuation offers a reliable, robust approach for axial displacement that provides many of the features needed to meet in the in vivo scanning requirements, including 1) high power/force density, 2) large motion displacement, 3) design flexibility, and 4) variety in choice of driving medium. The actuation speed is inherently less than that for MEMS-based electrostatic, thermal, and electromagnetic approaches, but a recent study has shown that pneumatic (air-driven) actuators can achieve axial motions as large as 300 urn at 5 Hz.86 This bandwidth is sufficient for the dual axes confocal microscope to achieve vertical cross-sectional images of 500 jam penetration depth using 785 nm light.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA136429-04
Application #
8324703
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$67,420
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Joshi, Bishnu P; Pant, Asha; Duan, Xiyu et al. (2016) Multimodal Video Colonoscope for Targeted Wide-Field Detection of Nonpolypoid Colorectal Neoplasia. Gastroenterology 150:1084-1086
Joshi, Bishnu P; Duan, Xiyu; Kwon, Richard S et al. (2016) Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia. Endoscopy 48:A1-A13
Zhou, Juan; Joshi, Bishnu P; Duan, Xiyu et al. (2015) EGFR Overexpressed in Colonic Neoplasia Can be Detected on Wide-Field Endoscopic Imaging. Clin Transl Gastroenterol 6:e101
Khondee, Supang; Rabinsky, Emily F; Owens, Scott R et al. (2015) Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles. J Control Release 199:114-21
Atreya, Raja; Neumann, Helmut; Neufert, Clemens et al. (2014) In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease. Nat Med 20:313-8
Qiu, Zhen; Khondee, Supang; Duan, Xiyu et al. (2014) Vertical cross-sectional imaging of colonic dysplasia in vivo with multi-spectral dual axes confocal endomicroscopy. Gastroenterology 146:615-7
Khondee, Supang; Wang, Thomas D (2013) Progress in molecular imaging in endoscopy and endomicroscopy for cancer imaging. J Healthc Eng 4:1-22
Sturm, Matthew B; Piraka, Cyrus; Elmunzer, B Joseph et al. (2013) In vivo molecular imaging of Barrett's esophagus with confocal laser endomicroscopy. Gastroenterology 145:56-58
Liu, Zhongyao; Miller, Sharon J; Joshi, Bishnu P et al. (2013) In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide. Gut 62:395-403
Sturm, Matthew B; Joshi, Bishnu P; Lu, Shaoying et al. (2013) Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: first-in-human results. Sci Transl Med 5:184ra61

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