Microendoscopic imaging is rapidly becoming an increasingly important field of biomedical imaging. With the ability to provide clinicians histologc information at the point of care during endoscopic procedures, it will be possible to better target surgical biopsies and improve clinical decision-making. One approach employs a flexible, coherent fiber bundle image guide coupled to a simple fluorescent microscope to generate images when in contact with fluorescently labeled epithelial tissues. A significant limitation of this epi-illumination strategy is lack of penetration depth in highly scattering tissues. In order o improve the diagnostic efficacy of this device, we propose a fiber bundle microendoscope imaging system employing a novel off-axis near infrared illumination fiber;the fiber bundle will be used to image the remitted diffusely reflected light. With the use of well-developed Monte Carlo forward models of photon propagation through tissue, we can effectively predict the pattern of diffuse reflection in three dimensions for a given distribution of absorbers in scatterig tissue. The pattern of diffusely reflected light remitted from the surface of tissue and collected y the image guide bundle can be predicted using this modeling approach. Using absorbing materials, it will also be possible to develop layered optical phantoms with discrete heterogeneities that can be quantitatively analyzed using the modified microendoscope. These optical phantoms will consist of systems of increasing complexity, comprising simple absorbing dyes, tuned NIR absorbed gold nanocages, and labeled cells in a collagen suspension. These phantoms will enable clear comparisons between simulated Monte Carlo estimates of performance, and actual experimental measurements. Imaging of diffusely reflected light will demonstrate the use of optically absorbing contrast agents, including molecule-specific nanomaterials, which have been optimized to absorb in the NIR wavelength range. The proposed imaging system will allow the use of these agents using a simple fiber bundle microendoscope device, and enable interrogation of deep structures within epithelial tissues. We believe this approach will greatly broaden the range of available contrast agents to fiber bundle microendoscopes, and significantly improve the capability of this technique across a range of translational applications.

Public Health Relevance

Microendoscopy is a promising imaging technique capable of presenting high-resolution images of tissue at the point-of-care;this information can help clinicians better target surgical biopsies in order to improve the early detection of cancer in suspicious lesions. Most microendoscopes rely on fluorescence or reflectance contrast to generate images;these approaches are somewhat limited due to penetration depth through tissue. This proposal aims to develop a microendoscope based on diffuse reflectance imaging, which can detect absorption in tissue at greater depths, and take advantage of emerging molecular-specific functionalized gold nanoparticle-based exogenous contrast agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA182052-01
Application #
8622318
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (O1))
Program Officer
Baker, Houston
Project Start
2014-01-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$68,140
Indirect Cost
$18,140
Name
University of Arkansas at Fayetteville
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
191429745
City
Fayetteville
State
AR
Country
United States
Zip Code
72701
Prieto, Sandra P; Lai, Keith K; Laryea, Jonathan A et al. (2016) Quantitative analysis of ex vivo colorectal epithelium using an automated feature extraction algorithm for microendoscopy image data. J Med Imaging (Bellingham) 3:024502
Greening, Gage J; Rajaram, Narasimhan; Muldoon, Timothy J (2016) In vivo measurement of non-keratinized squamous epithelium using a spectroscopic microendoscope with multiple source-detector separations. Proc SPIE Int Soc Opt Eng 9715:
Prieto, Sandra P; Greening, Gage J; Lai, Keith K et al. (2016) Quantitative structural markers of colorectal dysplasia in a cross sectional study of ex vivo murine tissue using label-free multiphoton microscopy. Proc SPIE Int Soc Opt Eng 9712:
Greening, Gage J; James, Haley M; Dierks, Mary K et al. (2016) Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe. Sci Rep 6:26734
Prieto, Sandra P; Powless, Amy J; Lai, Keith et al. (2015) Qualitative and quantitative comparison of colonic microendoscopy image features to histopathology. Proc SPIE Int Soc Opt Eng 9328:93280B
Greening, Gage J; Powless, Amy J; Hutcheson, Joshua A et al. (2015) Design and validation of a diffuse reflectance and spectroscopic microendoscope with poly(dimethylsioxane)-based phantoms. Proc SPIE Int Soc Opt Eng 9332:93320R
Prieto, Sandra P; Powless, Amy J; Boice, Jackson W et al. (2015) Proflavine Hemisulfate as a Fluorescent Contrast Agent for Point-of-Care Cytology. PLoS One 10:e0125598
Greening, Gage J; James, Haley M; Powless, Amy J et al. (2015) Fiber-bundle microendoscopy with sub-diffuse reflectance spectroscopy and intensity mapping for multimodal optical biopsy of stratified epithelium. Biomed Opt Express 6:4934-50
Greening, Gage J; Istfan, Raeef; Higgins, Laura M et al. (2014) Characterization of thin poly(dimethylsiloxane)-based tissue-simulating phantoms with tunable reduced scattering and absorption coefficients at visible and near-infrared wavelengths. J Biomed Opt 19:115002