Jennifer Kehlet Barton

Interests

Teaching

Biomedical EngineeringBioinstrumentation

Research

Biomedical OpticsOptical Coherence TomographyFluorescence SpectroscopyTissue OpticsColon CancerOvarian Cancer

Courses

Scholarly Contributions

Books

• Barton, J. K., Utzinger, U., & Tumlinson, A. R. (2015). Combined Endoscopic Optical Coherence Tomography and Laser Induced Fluorescence in Optical Coherence Tomography: Technology and Applications , Drexler and Fujimoto. Springer.

Journals/Publications

• Howard, C., Rice, P. F., Keenan, M., Dominguez-Cooks, J., Heusinkveld, J., Hsu, C. H., & Barton, J. K. (2022). Study of fallopian tube anatomy and mechanical properties to determine pressure limits for endoscopic exploration. Journal of histotechnology, 1-11.
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  Falloposcopy is the endoscopic examination of the fallopian tubes, which are challenging to access due to their deep body location, small opening from the uterus, and lumen filled with plicae. We and others have developed endoscopes that are inserted through the uterus guided by a hysteroscope into the tubal ostium. To better understand how to utilize these endoscopes either as standalone devices or in concert with everting delivery balloons, a preliminary study of anatomy and mechanical behavior was performed on porcine and human fallopian tubes. Segments of fallopian tubes from the isthmus, ampulla and infundibulum were inflated with saline either to bursting or held at sub-burst pressures with saline or a saline-filled balloon. Formalin fixed, paraffin embedded tissue sections stained with Masson's trichrome were examined for damage to the mucosa and muscularis. Porcine fallopian tubes tolerated saline pressurization at 15 psi for 1 minute without morphological damage. Balloon inflation to 15 psi caused no apparent damage to the muscle layer or rupture of the fallopian tube, but balloon movement within the tube can denude the mucosal epithelial layer. Human fallopian tubes averaged higher burst pressure values than porcine tubes. Under pressurization, the external tube diameter expanded by minimal to moderate amounts. Human and porcine tissues were similar in histological appearance. These studies suggest that moderate pressurization is acceptable but will not appreciably expand the fallopian tube diameter. The results also indicate that pigs are a reasonable model to study damage from falloscopy as seen in human tissue.
• Schwartz, D., Sawyer, T. W., Thurston, N., Ditzler, G., & Barton, J. K. (2022). Ovarian Cancer Detection Using Optical Coherence Tomography and Convolutional Neural Networks. Neural Computing and Applications, 34(11), 8977-8987.
• Cordova, R., Kiekens, K., Burrell, S., Drake, W., Kmeid, Z., Rice, P., Rocha, A., Diaz, S., Yamada, S., Yozwiak, M., Nelson, O. L., Rodriguez, G. C., Heusinkveld, J., Shih, I. M., Alberts, D. S., & Barton, J. K. (2021). Sub-millimeter endoscope demonstrates feasibility of in vivo reflectance imaging, fluorescence imaging, and cell collection in the fallopian tubes. Journal of biomedical optics, 26(7).
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  Most cases of high-grade serous ovarian carcinoma originate as serous tubal intraepithelial carcinoma (STIC) lesions in the fallopian tube epithelium (FTE), enabling early endoscopic detection.
• Kiekens, K. C., Vega, D., Thurgood, H. T., Galvez, D., McGregor, D. J., Sawyer, T. W., & Barton, J. K. (2021). Effect of an Added Mass on the Vibration Characteristics for Raster Scanning of a Cantilevered Optical Fiber. Journal of engineering and science in medical diagnostics and therapy, 4(2), 021007.
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  Piezoelectric tube actuators with cantilevered optical fibers have enabled the miniaturization of scanning image acquisition techniques for endoscopic implementation. To achieve raster scanning for such a miniaturized system, the first resonant frequency should be of the order of 10 s of Hz. We explore adding a mass at an intermediate location along the length of the fiber to alter the resonant frequencies of the system. We provide a mathematical model to predict resonant frequencies for a cantilevered beam with an intermediate mass. The theoretical and measured data match well for various fiber lengths, mass sizes, and mass attachment locations along the fiber.
• Larson, M. C., Gmitro, A. F., Utzinger, U., Rouse, A. R., Woodhead, G. J., Carlson, Q., Hennemeyer, C. T., & Barton, J. K. (2021). Using FDA-approved drugs as off-label fluorescent dyes for optical biopsies: from in silico design toproof-of-concept. Methods and applications in fluorescence, 9(3).
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  Optical biopsies bring the microscope to the patient rather than the tissue to the microscope, and may complement or replace the tissue-harvesting component of the traditional biopsy process with its associated risks. In general, optical biopsies are limited by the lack of endogenous tissue contrast and the small number of clinically approveddyes. This study tests multiple FDA-approved drugs that have structural similarity to research dyes as off-labelfluorescent alternatives to standardhematoxylin & eosin tissue stain. Numerous drug-dye combinations shown here may facilitate relatively safe and fastor possiblystaining of tissue, enabling real-time optical biopsies and other advanced microscopy technologies, which have implications for the speed and performance of tissue- and cellular-level diagnostics.
• Russell, S., Barton, J. K., Rodriguez, G., Zhang, H., & Alberts, D. S. (2021). Karyometry Identifies a Distinguishing Fallopian Tube Epithelium Phenotype in Subjects at High Risk for Ovarian Cancer. Analytical and Quantitative Cytopathology and Histopathology, 43(2), 44-51.
• Vega, D., Galvez, D., Romano, G., Kiekens, K., Pham, N., Heusinkveld, J., Hatch, K. D., Vaughn, A., & Barton, J. K. (2021). Triple modality co-register endoscope featuring wide field reflectance imaging, and high-resolution multiphoton and optical coherence microscopy. Journal of Optical Microsystems, 1(044502).
• Vega, D., Galvez, D., Romano, G., Pham, N. Y., Cordova, R., Aitken, M., Suebka, S., Heusinkveld, J., & Barton, J. K. (2021). Triple-modality co-registered endoscope featuring wide-field reflectance imaging, and high-resolution multiphoton and optical coherence microscopy. Proceedings of SPIE--the International Society for Optical Engineering, 1(4).
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  We present the design and feasibility testing of a multimodal co-registered endoscope based on a dual-path optical system integrated with a scanning piezo. This endoscope incorporates three different imaging modalities. A large field of view reflectance imaging system enables visualization of objects several millimeters in front of the endoscope, while optical coherence microscopy and multiphoton microscopy are employed in contact with tissue to further analyze suspicious areas. The optical system allows multiple different imaging modalities by employing a dual optical path. One path features a low numerical aperture and wide field of view to allow reflectance imaging of distant objects. The other path features a high numerical aperture and short working distance to allow microscopy techniques such as optical coherence microscopy and multiphoton microscopy. Images of test targets were obtained with each imaging modality to verify and characterize the imaging capabilities of the endoscope. The reflectance modality was demonstrated with a 561 nm laser to allow high contrast with blood vessels. It achieved a lateral resolution of 24.8 μm at 5 mm and a working distance from 5 mm to 30 mm. Optical coherence microscopy (OCM) was performed with a 1300 nm super-luminescent diode since this wavelength experiences low relative scattering to allow for deeper tissue imaging. Measured OCM lateral and axial resolution was 4.0 μm and 14.2 μm, respectively. Multiphoton microscopy (MPM) was performed with a custom 1400 nm femtosecond fiber laser, a wavelength suitable for exciting multiple exogenous and some endogenous fluorophores, as well as providing information on tissue composition through harmonic generation processes. A 4.0 μm MPM lateral resolution was measured.
• Kiekens, K. C., Romano, G., Galvez, D., Cordova, R., Heusinkveld, J., Hatch, K., Drake, W., Kmeid, Z., & Barton, J. K. (2020). Reengineering a falloposcope imaging system for clinical use. Translational Biophotonics, 2(4), e202000011.
• Sawyer, T. W., Koevary, J. W., Howard, C. C., Austin, O. J., Rice, P. F., Hutchens, G. V., Chambers, S. K., Connolly, D. C., & Barton, J. K. (2020). Fluorescence and Multiphoton Imaging for Tissue Characterization of a Model of Postmenopausal Ovarian Cancer. Lasers in surgery and medicine, 52(10), 993-1009.
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  To determine the efficacy of targeted fluorescent biomarkers and multiphoton imaging to characterize early changes in ovarian tissue with the onset of cancer.
• Vega, D., Sawyer, T. W., Pham, N. Y., & Barton, J. K. (2020). Use of embedded and patterned dichroic surfaces with reflective optical power to enable multiple optical paths in a micro-objective. Applied optics, 59(22), G71-G78.
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  We demonstrate the use of patterned dichroic surfaces with reflective optical power to create multiple optical paths in a single lens system. The application of these surfaces enables a micro-endoscope to accommodate multiple imaging technologies with only one optical system, making the packaging more compact and reliable. The optical paths are spectrally separated using different wavelengths for each path. The dichroic surfaces are designed such that the visible wavelengths transmit through the surfaces optically unaffected, but the near-infrared wavelengths are reflected in a telescope-like configuration with the curved dichroic surfaces providing reflective optical power. We demonstrate wide-field visible monochromatic imaging and microscopic near-infrared imaging using the same set of lenses. The on-axis measured resolution of the wide-field imaging configuration is approximately 14 µm, and the measured resolution of the microscopic imaging configuration is approximately 2 µm. Wide-field white-light imaging of an object is also demonstrated for a qualitative perspective on the imaging capabilities. Other configurations and applications in fields such as optical metrology are discussed to expand on the versatility of the demonstrated optical system.
• Barton, J. K., & Kiekens, K. C. (2019). 3D printed lens for depth of field imaging. OSA Continuum, 2(11), 3019-3025.
• Hoyer, P. B., Rice, P. F., Howard, C. C., Koevary, J. W., Dominguez Cooks, J. P., Hutchens, G. V., Chambers, S. K., Craig, Z. R., Connolly, D. C., & Barton, J. K. (2019). Comparison of Reproductive Function in Female Transgenic and Wildtype C57BL/6 Mice. Comparative medicine, 69(1), 16-21.
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  Transgenic (TAg) mice express the oncogenic virus SV40 in Mullerian epithelial cells. Female TAg mice spontaneously develop epithelial ovarian carcinoma, the most common type of ovarian cancer in women. Female TAg mice are infertile, but the reason has not been determined. We therefore investigated whether female TAg mice undergo puberty, demonstrate follicular development, maintain regular cycles, and ovulate. Ovarian cancers in women commonly develop after menopause. The occupational chemical 4-vinylcyclohexene diepoxide (VCD) accelerates follicle degeneration in the ovaries of rats and mice, causing early ovarian failure. We therefore used VCD dosing of mice to develop an animal model for menopause. The purpose of this study was to characterize reproductive parameters in female TAg mice and to investigate whether the onset of ovarian failure due VCD dosing differed between female TAg and WT C57BL/6 mice. As in WT female mice, TAg female mice underwent puberty (vaginal opening) and developed cyclicity in patterns that were similar between the groups. Vehicle-only TAg mice had fewer ovulations (numbers of corpora lutea) than WT animals. VCD exposure delayed the onset of puberty (day of first estrus) in TAg as compared with WT mice. Morphologic evaluation of ovaries revealed many more degenerating follicles in TAg mice than WT mice, and more VCD-dosed TAg mice were in ovarian failure than VCD-dosed WT mice. These results suggest that despite showing similar onset of sexual maturation, TAg mice have increased follicular degeneration and fewer ovulations than WT. These features may contribute to the inability of female TAg mice to reproduce.
• Loh, T. Y., Goldberg, M. S., Falsey, R. R., Barton, J. K., Sagerman, P., & Goldberg, G. N. (2019). Insight into the mechanisms of type III minocycline-induced pigmentation removal: A case of repeated immediate pigment clearing with the Q-switched 755-nm alexandrite laser over a 13-year period. JAAD case reports, 5(10), 865-867.
• Qin, Y., Ou, Y. H., Cromey, B., Batjargal, O., Barton, J. K., & Kieu, K. (2019). Watt-level all-fiber optical parametric chirped-pulse amplifier working at 1300  nm. Optics letters, 44(14), 3422-3425.
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  We report watt-level average output power near 1300 nm from an all-fiber ultrafast optical parametric chirped-pulse amplifier. A compressed output pulse duration of ∼300  fs is achieved. Multiphoton imaging of a variety of samples carried out with this light source shows a good signal-to-noise ratio. With the demonstrated imaging capability, we believe that this high-power ultrafast laser source addresses a key need in deep tissue multiphoton microscopy.
• Sawyer, T. W., Koevary, J. W., Rice, F. P., Howard, C. C., Austin, O. J., Connolly, D. C., Cai, K. Q., & Barton, J. K. (2019). Quantification of multiphoton and fluorescence images of reproductive tissues from a mouse ovarian cancer model shows promise for early disease detection. Journal of biomedical optics, 24(9), 1-16.
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  Ovarian cancer is the deadliest gynecologic cancer due predominantly to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Multiphoton microscopy (MPM) is a relatively new imaging technique sensitive to endogenous fluorophores, which has tremendous potential for clinical diagnosis, though it is limited in its application to the ovaries. Wide-field fluorescence imaging (WFI) has been proposed as a complementary technique to MPM, as it offers high-resolution imagery of the entire organ and can be tailored to target specific biomarkers that are not captured by MPM imaging. We applied texture analysis to MPM images of a mouse model of ovarian cancer. We also conducted WFI targeting the folate receptor and matrix metalloproteinases. We find that texture analysis of MPM images of the ovary can differentiate between genotypes, which is a proxy for disease, with high statistical significance (p 
• Sawyer, T. W., Rice, P. F., Sawyer, D. M., Koevary, J. W., & Barton, J. K. (2019). Evaluation of segmentation algorithms for optical coherence tomography images of ovarian tissue. Journal of medical imaging (Bellingham, Wash.), 6(1), 014002.
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  Ovarian cancer has the lowest survival rate among all gynecologic cancers predominantly due to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Optical coherence tomography (OCT) is an emerging technique that provides depth-resolved, high-resolution images of biological tissue in real-time and demonstrates great potential for imaging of ovarian tissue. Mouse models are crucial to quantitatively assess the diagnostic potential of OCT for ovarian cancer imaging; however, due to small organ size, the ovaries must first be separated from the image background using the process of segmentation. Manual segmentation is time-intensive, as OCT yields three-dimensional data. Furthermore, speckle noise complicates OCT images, frustrating many processing techniques. While much work has investigated noise-reduction and automated segmentation for retinal OCT imaging, little has considered the application to the ovaries, which exhibit higher variance and inhomogeneity than the retina. To address these challenges, we evaluate a set of algorithms to segment OCT images of mouse ovaries. We examine five preprocessing techniques and seven segmentation algorithms. While all preprocessing methods improve segmentation, Gaussian filtering is most effective, showing an improvement of . Of the segmentation algorithms, active contours performs best, segmenting with an accuracy of compared with manual segmentation. Even so, further optimization could lead to maximizing the performance for segmenting OCT images of the ovaries.
• Akhoundi, F., Qin, Y., Peyghambarian, N., Barton, J. K., & Kieu, K. (2018). Compact fiber-based multi-photon endoscope working at 1700 nm. Biomedical optics express, 9(5), 2326-2335.
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  We present the design, implementation and performance analysis of a compact multi-photon endoscope based on a piezo electric scanning tube. A miniature objective lens with a long working distance and a high numerical aperture (≈ 0.5) is designed to provide a diffraction limited spot size. Furthermore, a 1700 wavelength femtosecond fiber laser is used as an excitation source to overcome the scattering of biological tissues and reduce water absorption. Therefore, the novel optical system along with the unique wavelength allows us to increase the imaging depth. We demonstrate that the endoscope is capable of performing third and second harmonic generation (THG/SHG) and three-photon excitation fluorescence (3PEF) imaging over a large field of view (> 400 ) with high lateral resolution (2.2 ). The compact and lightweight probe design makes it suitable for minimally-invasive in-vivo imaging as a potential alternative to surgical biopsies.
• Barton, J. K., Connolly, D. C., Craig, Z. R., Chambers, S. K., Hutchens, G. V., Dominguez Cooks, J. P., Koevary, J. W., Howard, C. C., Rice, P. F., & Hoyer, P. (2018). Comparison of Markers of Reproductive Function in Female C57Bl/6 versus TgMISIIR-TAg Transgenic Mice: Effect of VCD exposure on Ovarian Failure.. Comparative Medicine.
• Batjargal, O., Ou, Y. H., Keikens, K., Barton, J. K., & Kieu, K. (2018). All-fiber dissipative soliton Raman laser based on phosphosilicate fiber. IEEE photonics technology letters : a publication of the IEEE Laser and Electro-optics Society, 30(21), 1846-1849.
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  We propose and demonstrate an all-fiber, synchronously pumped Raman laser based on phosphosilicate fiber (P-doped fiber) for deep tissue multiphoton imaging. The laser operates in a dissipative soliton regime and produces 2.2 ps chirped pulses (compressible to 317 fs) with energy up to 9.2 nJ, 0.3 W average power and at 1240 nm center wavelength. We have also found a new cross-polarization Raman lasing operation that offers access to an important wavelength near 930 nm for calcium imaging.
• Rice, P. F., Ehrichs, K. G., Jones, M. S., Chen, H., Hsu, C. H., Abril, E. R., Nagle, R. B., Besselsen, D. G., Barton, J. K., & Ignatenko, N. A. (2018). Does Mutated K-RAS Oncogene Attenuate the Effect of Sulindac in Colon Cancer Chemoprevention?. Cancer prevention research (Philadelphia, Pa.), 11(1), 16-26.
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  The NSAID sulindac has been successfully used alone or in combination with other agents to suppress colon tumorigenesis in patients with genetic predisposition and also showed its efficacy in prevention of sporadic colon adenomas. At the same time, some experimental and clinical reports suggest that a mutant K-RAS oncogene may negate sulindac antitumor efficacy. To directly assess sulindac activity at suppressing premalignant lesions carrying K-RAS mutation, we utilized a novel mouse model with an inducible colon-specific expression of the mutant K-ras oncogene (K-rasG12D ). Tumor development and treatment effects were monitored by minimally invasive endoscopic Optical coherence tomography. Expression of the mutant K-ras allele accelerated azoxymethane (AOM)-induced colon carcinogenesis in C57BL/6 mice, a strain otherwise resistant to this carcinogen. Sulindac completely prevented AOM-induced tumor formation in K-ras wild-type (K-ras wt) animals. In K-rasG12D -mutant mice, a 38% reduction in tumor number, an 83% reduction in tumor volume (P ≤ 0.01) and an increase in the number of adenoma-free mice (P = 0.04) were observed. The partial response of K-RasG12D animals to sulindac treatment was evident by the decrease in mucosal thickness (P < 0.01) and delay in progression of the precancerous aberrant crypt foci to adenomas. Molecular analyses showed significant induction in cyclooxygenase 2 (COX-2), cleaved caspase-3 (CC3), and Ki-67 expression by AOM, but not sulindac treatment, in all genotypes. Our data underscore the importance of screening for K-RAS mutations in individuals with colon polyps to provide more personalized interventions targeting mutant K-RAS signaling pathways. Cancer Prev Res; 11(1); 16-26. ©2017 AACR.
• Sawyer, T. W., Chandra, S., Rice, P. F., Koevary, J. W., & Barton, J. K. (2018). Three-dimensional texture analysis of optical coherence tomography images of ovarian tissue. Physics in medicine and biology, 63(23), 235020.
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  Ovarian cancer has the lowest survival rate among all gynecologic cancers due to predominantly late diagnosis. Optical coherence tomography (OCT) has been applied successfully to experimentally image the ovaries in vivo; however, a robust method for analysis is still required to provide quantitative diagnostic information. Recently, texture analysis has proved to be a useful tool for tissue characterization; unfortunately, existing work in the scope of OCT ovarian imaging is limited to only analyzing 2D sub-regions of the image data, discarding information encoded in the full image area, as well as in the depth dimension. Here we address these challenges by testing three implementations of texture analysis for the ability to classify tissue type. First, we test the traditional case of extracted 2D regions of interest; then we extend this to include the entire image area by segmenting the organ from the background. Finally, we conduct a full volumetric analysis of the image volume using 3D segmented data. For each case, we compute features based on the Grey-Level Co-occurence Matrix and also by introducing a new approach that evaluates the frequency distribution in the image by computing the energy density. We test these methods on a mouse model of ovarian cancer to differentiate between age, genotype, and treatment. The results show that the 3D application of texture analysis is most effective for differentiating tissue types, yielding an average classification accuracy of 78.6%. This is followed by the analysis in 2D with the segmented image volume, yielding an average accuracy of 71.5%. Both of these improve on the traditional approach of extracting square regions of interest, which yield an average classification accuracy of 67.7%. Thus, applying texture analysis in 3D with a fully segmented image volume is the most robust approach to quantitatively characterizing ovarian tissue.
• Black, K. C., Kirkpatrick, N. D., Troutman, T. S., Xu, L., Vagner, J., Gillies, R. J., Barton, J. K., Utzinger, U., & Romanowski, M. (2008). Gold nanorods targeted to delta opioid receptor: plasmon-resonant contrast and photothermal agents. Molecular imaging, 7(1), 50-7.
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  Molecularly targeted gold nanorods were investigated for applications in both diagnostic imaging and disease treatment with cellular resolution. The nanorods were tested in two genetically engineered cell lines derived from the human colon carcinoma HCT-116, a model for studying ligand-receptor interactions. One of these lines was modified to express delta opioid receptor (deltaOR) and green fluorescent protein, whereas the other was receptor free and expressed a red fluorescent protein, to serve as the control. Deltorphin, a high-affinity ligand for deltaOR, was stably attached to the gold nanorods through a thiol-terminated linker. In a mixed population of cells, we demonstrated selective imaging and destruction of receptor-expressing cells while sparing those cells that did not express the receptor. The molecularly targeted nanorods can be used as an in vitro ligand-binding and cytotoxic treatment assay platform and could potentially be applied in vivo for diagnostic and therapeutic purposes with endoscopic technology.
• Chandra, S., Nymeyer, A. C., Rice, P. F., Gerner, E. W., & Barton, J. K. (2017). Intermittent Dosing with Sulindac Provides Effective Colorectal Cancer Chemoprevention in the Azoxymethane-Treated Mouse Model. Cancer prevention research (Philadelphia, Pa.), 10(8), 459-466.
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  Sulindac is an NSAID that can provide effective chemoprevention for colorectal cancer. In this study, alternative dosing regimens of sulindac were evaluated for their chemoprevention effectiveness in the azoxymethane-treated A/J mouse model of colorectal cancer. High-resolution endoscopic optical coherence tomography was utilized to time-serially measure tumor number and tumor burden in the distal colon as the biological endpoints. Four treatment groups were studied: (i) daily for 20 weeks (sulindac-daily); (ii) for 2 weeks, then no sulindac for 2 weeks, cycle repeated 5 times (sulindac-2); (iii) for 10 weeks ("on"), then no sulindac for 10 weeks ("off"; sulindac-10); and (iv) no sulindac (sulindac-none). Sulindac-2 and sulindac-daily had statistically significantly lower final tumor counts and slopes (change in number of tumors per week) when compared with sulindac-none (P < 0.0001). All of the treatment groups had statistically significantly lower final tumor burdens and slopes when compared with sulindac-none (P < 0.001). There was a prolonged latency period in the sulindac-10 group, with no significant difference between the "off" portion of this treatment and sulindac-none. These results suggest that, although daily doses of sulindac provide the most optimal effects, intermittent doses of sulindac in a 50% duty cycle with an overall 4-week period (sulindac-2 model) can provide highly effective chemoprevention of colorectal cancer in this model. After cessation of sulindac treatment (sulindac-10 "off"), there is no evidence of either a persistent chemopreventive effect or a rebound effect. Cancer Prev Res; 10(8); 459-66. ©2017 AACR.
• Howlett, I. D., Han, W., Gordon, M., Rice, P., Barton, J. K., & Kostuk, R. K. (2017). Volume holographic imaging endoscopic design and construction techniques. Journal of biomedical optics, 22(5), 56010.
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  A reflectance volume holographic imaging (VHI) endoscope has been designed for simultaneous in vivo imaging of surface and subsurface tissue structures. Prior utilization of VHI systems has been limited to ex vivo tissue imaging. The VHI system presented in this work is designed for laparoscopic use. It consists of a probe section that relays light from the tissue sample to a handheld unit that contains the VHI microscope. The probe section is constructed from gradient index (GRIN) lenses that form a 1:1 relay for image collection. The probe has an outer diameter of 3.8 mm and is capable of achieving 228.1 ?? lp / mm resolution with 660-nm Kohler illumination. The handheld optical section operates with a magnification of 13.9 and a field of view of 390 ?? ? m × 244 ?? ? m . System performance is assessed through imaging of 1951 USAF resolution targets and soft tissue samples. The system has also passed sterilization procedures required for surgical use and has been used in two laparoscopic surgical procedures.
• Howlett, I. D., Han, W., Rice, P., Barton, J. K., & Kostuk, R. K. (2017). Wavelength-coded volume holographic imaging endoscope for multidepth imaging. Journal of biomedical optics, 22(10), 1-4.
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  A wavelength-coded volume holographic imaging (WC-VHI) endoscope system capable of simultaneous multifocal imaging is presented. The system images light from two depths separated by 100  μm in a tissue sample by using axial chromatic dispersion of a gradient index probe in combination with two light-emitting diode sources and a multiplexed volume hologram to separate the images. This system is different from previous VHI systems in that it uses planar multiplexed gratings and does not require curved holographic gratings. This results in improved lateral imaging resolution from 228.1 to 322.5  lp/mm. This letter describes the design and fabrication of the WC-VHI endoscope and experimental images of hard and soft resolution targets and biological tissue samples to illustrate the performance properties.
• Keenan, M., Tate, T. H., Kieu, K., Black, J. F., Utzinger, U., & Barton, J. K. (2017). Design and characterization of a combined OCT and wide field imaging falloposcope for ovarian cancer detection. Biomedical optics express, 8(1), 124-136.
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  Early detection of ovarian cancer is only achieved in around 20% of women due to lack of effective screening. We propose a method for surveillance of high risk women based on a microendoscope introduced transvaginally to image the fallopian tubes and ovaries. This requires extreme miniaturization of the optics and catheter sheath. We describe the design of a falloposcope that combines optical coherence tomography (OCT) and wide field imaging into a sub-1 mm diameter package. We characterize the systems and show that they provide contrast on ex-vivo samples of ovary and fallopian tube. In addition, we show the mechanical performance of the endoscope in an anatomically correct model of the female reproductive tract.
• Tate, T. H., Keenan, M., Black, J., Utzinger, U., & Barton, J. K. (2017). Ultraminiature optical design for multispectral fluorescence imaging endoscopes. Journal of biomedical optics, 22(3), 36013.
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  A miniature wide-field multispectral endoscopic imaging system was developed enabling reflectance and fluorescence imaging over a broad wavelength range. At 0.8-mm diameter, the endoscope can be utilized for natural orifice imaging in small lumens such as the fallopian tubes. Five lasers from 250 to 642 nm are coupled into a 125 - ? m diameter multimode fiber and transmitted to the endoscope distal tip for illumination. Ultraviolet and blue wavelengths excite endogenous fluorophores, which can provide differential fluorescence emission images for health and disease. Visible wavelengths provide reflectance images that can be combined for pseudo-white-light imaging and navigation. Imaging is performed by a 300 - ? m diameter three-element lens system connected to a 3000-element fiber. The lens system was designed for a 70-deg full field of view, working distance from 3 mm to infinity, and 40% contrast at the Nyquist cutoff of the fiber bundle. Measured performance characteristics are near design goals. The endoscope was utilized to obtain example monochromatic, pseudo-white-light, and composite fluorescence images of phantoms and porcine reproductive tract. This work shows the feasibility of packaging a highly capable multispectral fluorescence imaging system into a miniature endoscopic system that may have applications in early detection of cancer.
• Barton, J. K., Amirsolaimani, B., Rice, P., Hatch, K., & Kieu, K. (2016). Three-photon imaging of ovarian cancer. PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII, 9689.
• Harpel, K., Leung, S., Rice, P. F., Jones, M., Barton, J. K., & Bommireddy, R. (2016). Imaging colon cancer development in mice: IL-6 deficiency prevents adenoma in azoxymethane-treated Smad3 knockouts. Physics in medicine and biology, 61(3), N60-9.
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  The development of colorectal cancer in the azoxymethane-induced mouse model can be observed by using a miniaturized optical coherence tomography (OCT) imaging system. This system is uniquely capable of tracking disease development over time, allowing for the monitoring of morphological changes in the distal colon due to tumor development and the presence of lymphoid aggregates. By using genetically engineered mouse models deficient in Interleukin 6 (IL-6) and Smad family member 3 (Smad3), the role of inflammation on tumor development and the immune system can be elucidated. Smad3 knockout mice develop inflammatory response, wasting, and colitis associated cancer while deficiency of proinflammatory cytokine IL-6 confers resistance to tumorigenesis. We present pilot data showing that the Smad3 knockout group had the highest tumor burden, highest spleen weight, and lowest thymus weight. The IL-6 deficiency in Smad3 knockout mice prevented tumor development, splenomegaly, and thymic atrophy. This finding suggests that agents that inhibit IL-6 (e.g. anti-IL-6 antibody, non-steroidal anti-inflammatory drugs [NSAIDs], etc.) could be used as novel therapeutic agents to prevent disease progression and increase the efficacy of anti-cancer agents. OCT can also be useful for initiating early therapy and assessing the benefit of combination therapy targeting inflammation.
• Keenan, M., Howard, C., Tate, T., McGuiness, I., Sauer-Budge, A., Black, J., Utzinger, U., & Barton, J. K. (2016). Design of an everting balloon to deploy a microendoscope to the fallopian tubes.. PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII, 9689.
• Tate, T. H., Baggett, B., Rice, P. F., Koevary, J. W., Orsinger, G. V., Nymeyer, A. C., Welge, W. A., Saboda, K., Roe, D. J., Hatch, K. D., Chambers, S. K., Utzinger, U., & Barton, J. K. (2016). Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early-stage cancer detection. Journal of biomedical optics, 21(5), 56005.
• Welge, W. A., & Barton, J. K. (2016). Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer. ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III, 9691.
• Welge, W. A., & Barton, J. K. (2017). In vivo endoscopic Doppler optical coherence tomography imaging of the colon. Lasers in surgery and medicine.
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  Colorectal cancer (CRC) remains the second deadliest cancer in the United States. Several screening methods exist; however, detection of small polyps remains a challenge. Optical coherence tomography (OCT) has been demonstrated to be capable of detecting lesions as small as 1 mm in the mouse colon, but detection is based on measuring a doubling of the mucosa thickness. The colon microvasculature may be an attractive biomarker of early tumor development because tumor vessels are characterized by irregular structure and dysfunction. Our goal was to develop an endoscopic method of detecting and segmenting colon vessels using Doppler OCT to enable future studies for improving early detection and development of novel chemopreventive agents.
• Black, J. F., Tate, T., Keenan, M., Swan, E., Utzinger, U., & Barton, J. (2015). A six-color four-laser mobile platform for Multi-spectral Fluorescence Imaging Endoscopy. ENDOSCOPIC MICROSCOPY X; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE II, 9304.
• Black, J., Tate, T., Keenan, M., Swan, E., Utzinger, U., & Barton, J. (2015). A Six-Color Four-Laser Mobile Platform for Multi-Spectral Fluorescence Imaging Endoscopy. 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO).
• Carbary-Ganz, J. L., Welge, W. A., Barton, J. K., & Utzinger, U. (2015). In vivo molecular imaging of colorectal cancer using quantum dots targeted to vascular endothelial growth factor receptor 2 and optical coherence tomography/laser-induced fluorescence dual-modality imaging. Journal of biomedical optics, 20(9), 096015.
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  Optical coherence tomography/laser induced fluorescence (OCT/LIF) dual-modality imaging allows for minimally invasive, nondestructive endoscopic visualization of colorectal cancer in mice. This technology enables simultaneous longitudinal tracking of morphological (OCT) and biochemical (fluorescence) changes as colorectal cancer develops, compared to current methods of colorectal cancer screening in humans that rely on morphological changes alone. We have shown that QDot655 targeted to vascular endothelial growth factor receptor 2 (QD655-VEGFR2) can be applied to the colon of carcinogen-treated mice and provides significantly increased contrast between the diseased and undiseased tissue with high sensitivity and specificity ex vivo. QD655-VEGFR2 was used in a longitudinal in vivo study to investigate the ability to correlate fluorescence signal to tumor development. QD655-VEGFR2 was applied to the colon of azoxymethane (AOM-) or saline-treated control mice in vivo via lavage. OCT/LIF images of the distal colon were taken at five consecutive time points every three weeks after the final AOM injection. Difficulties in fully flushing unbound contrast agent from the colon led to variable background signal; however, a spatial correlation was found between tumors identified in OCT images, and high fluorescence intensity of the QD655 signal, demonstrating the ability to detect VEGFR2 expressing tumors in vivo.
• Keenan, M. R., Leung, S. J., Rice, P. S., Wall, R. A., & Barton, J. K. (2015). Dual optical modality endoscopic imaging of cancer development in the mouse colon. Lasers in surgery and medicine, 47(1), 30-9.
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  We utilize a miniature, dual-modality endoscope that combines fluorescence-based surface magnifying chromoendoscopy (SMC) and optical coherence tomography (OCT) to follow the anatomical changes that occur during adenoma development in the mouse colon.
• LeGendre-McGhee, S., Rice, P. S., Wall, R. A., Sprute, K. J., Bommireddy, R., Luttman, A. M., Nagle, R. B., Abril, E. R., Farrell, K., Hsu, C., Roe, D. J., Gerner, E. W., Ignatenko, N. A., & Barton, J. K. (2015). Time-serial Assessment of Drug Combination Interventions in a Mouse Model of Colorectal Carcinogenesis Using Optical Coherence Tomography. Cancer growth and metastasis, 8(Suppl 1), 63-80.
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  Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX)-2, β-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups (P < 0.0001), but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency (P = 0.04). In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models.
• Leung, S. J., Rice, P. S., & Barton, J. K. (2015). In vivo molecular mapping of the tumor microenvironment in an azoxymethane-treated mouse model of colon carcinogenesis. Lasers in surgery and medicine, 47(1), 40-9.
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  Development of miniaturized imaging systems with molecular probes enables examination of molecular changes leading to initiation and progression of colorectal cancer in an azoxymethane (AOM)-induced mouse model of the disease. Through improved and novel studies of animal disease models, more effective diagnostic and treatment strategies may be developed for clinical translation. We introduce use of a miniaturized multimodal endoscope with lavage-delivered fluorescent probes to examine dynamic microenvironment changes in an AOM-treated mouse model.
• Swan, E., Tate, T., Keenan, M., Black, J. F., Utzinger, U., & Barton, J. (2015). Stray light mitigation in a novel endoscope for fallopian tubes. ENDOSCOPIC MICROSCOPY X; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE II, 9304.
• Tate, T., Baggett, B., Rice, P., Watson, J., Orsinger, G., Nymeyer, A. C., Welge, W. A., Keenan, M., Saboda, K., Roe, D. J., Hatch, K., Chambers, S., Black, J., Utzinger, U., & Barton, J. (2015). Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection. ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC AND SURGICAL GUIDANCE SYSTEMS XIII, 9313.
• Utzinger, U., Barton, J. K., Black, J. F., Chambers, S. K., Hatch, K. D., Keenan, M., Orsinger, G., Watson, J., Baggett, B., & Tate, T. (2015). Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early stage cancer detection (abstract). Accepted for Presentation at: SPIE BIOS: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XIII.
• Welge, W. A., & Barton, J. K. (2015). Expanding Functionality of Commercial Optical Coherence Tomography Systems by Integrating a Custom Endoscope. PloS one, 10(9), e0139396.
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  Optical coherence tomography (OCT) is a useful imaging modality for detecting and monitoring diseases of the gastrointestinal tract and other tubular structures. The non-destructiveness of OCT enables time-serial studies in animal models. While turnkey commercial research OCT systems are plenty, researchers often require custom imaging probes. We describe the integration of a custom endoscope with a commercial swept-source OCT system and generalize this description to any imaging probe and OCT system. A numerical dispersion compensation method is also described. Example images demonstrate that OCT can visualize the mouse colon crypt structure and detect adenoma in vivo.
• Welge, W., & Barton, J. (2015). MILD TEMPERATURE HYPERTHERMIA INDUCING DOPPLER OPTICAL COHERENCE TOMOGRAPHY ENDOSCOPE FOR EARLY DETECTION OF COLORECTAL CANCER IN A MOUSE MODEL. LASERS IN SURGERY AND MEDICINE, 47, 49-49.
• Yang, M., Katz, J., Barton, J. K., Lai, W., & Jean, J. (2015). Using optical coherence tomography to examine additives in Chinese Song Jun glaze. Archaeometry, 57(5), 837-855.
• Carbary-Ganz, J. L., Barton, J. K., & Utzinger, U. (2014). Quantum dots targeted to vascular endothelial growth factor receptor 2 as a contrast agent for the detection of colorectal cancer. Journal of biomedical optics, 19(8), 086003.
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  We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.
• Howlett, I. D., Gordon, M., Brownlee, J. W., Barton, J. K., & Kostuk, R. K. (2014). Volume Holographic Reflection Endoscope for In-Vivo Ovarian Cancer Clinical Studies. Proceedings of SPIE--the International Society for Optical Engineering, 2014.
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  We present the design for an endoscopic system capable of imaging tissues of the ovary at two selected imaging depths simultaneously. The method utilizes a multiplexed volume hologram to select wavefronts from different depths within the tissue. It is the first demonstration of an endoscopic volume holographic imaging system. The endoscope uses both gradient index (GRIN) optical components and off the shelf singlet lenses to relay an image from the distal tip to the proximal end. The endoscope has a minimum diameter of 3.75 mm. The system length is 30 cm which is connected to a handle that includes the holographic components and optics that relay the image to a camera. Preliminary evaluation of the endoscope was performed with tissue phantoms and calibrated targets, which shows lateral resolution ≈ 4 μm at an operating wavelength of 660 nm. The hologram is recorded in phenanthraquinone doped poly methacrylate and is designed to produce images from two tissue depths. One image is obtained at the tissue surface and the second 70 μm below the surface. This method requires no mechanical scanning and acquires an image at the camera frame rate. The preliminary ex-vivo results show good correlation with histology sections of the same tissue sections.
• Keenan, M. R., Leung, S. J., Rice, P., Wall, R. A., & Barton, J. K. (2014). DUAL-MODALITY ENDOSCOPIC IMAGING OF CANCER IN MOUSE COLON. LASERS IN SURGERY AND MEDICINE, 46, 26-26.
• Orsinger, G. V., Watson, J. M., Gordon, M., Nymeyer, A. C., de Leon, E. E., Brownlee, J. W., Hatch, K. D., Chambers, S. K., Barton, J. K., Kostuk, R. K., & Romanowski, M. (2014). Simultaneous multiplane imaging of human ovarian cancer by volume holographic imaging. Journal of biomedical optics, 19(3), 36020.
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  Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis.
• Slayton, M. H., & Barton, J. K. (2014). Healing Tissue Response with ITU (Intense Therapy Ultrasound) in Musculoskeletal Tissue, Feasibility Study. 2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS), 1654-1657.
• Slayton, M., & Barton, J. (2014). FEASIBILITY OF MODULATING HEALING TISSUE RESPONSE BY ITU (INTENSE THERAPY ULTRASOUND) IN MUSCULOSKELETAL TISSUE. LASERS IN SURGERY AND MEDICINE, 46, 55-55.
• Tate, T. H., Keenan, M. R., Watson, J., Black, J. F., Barton, J. K., & Utzinger, U. (2014). OPTICAL IMAGING FALLOPOSCOPE FOR MINIMALLY INVASIVE OVARIAN CANCER DETECTION. LASERS IN SURGERY AND MEDICINE, 46(4), 369-369.
• Tate, T., Keenan, M., Swan, E., Black, J., Utzinger, U., & Barton, J. (2014). Optical design of an optical coherence tomography and multispectral fluorescence imaging endoscope to detect early stage ovarian cancer. INTERNATIONAL OPTICAL DESIGN CONFERENCE 2014, 9293.
• Wall, R. A., & Barton, J. K. (2014). Oblique incidence reflectometry: optical models and measurements using a side-viewing gradient index lens-based endoscopic imaging system. Journal of biomedical optics, 19(6), 067002.
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  A side-viewing, 2.3-mm diameter oblique incidence reflectometry endoscope has been designed to obtain optical property measurements of turbid samples. Light from a single-mode fiber is relayed obliquely onto the tissue with a gradient index lens-based distal optics assembly and the resulting diffuse reflectance profile is imaged and collected with a 30,000 element, 0.72 mm clear aperture fiber bundle. Sampling the diffuse reflectance in two-dimensions allows for fitting of the reflected intensity profile to a well-known theoretical model, permitting the extraction of both absorption and reduced scattering coefficients of the tissue sample. Models and measurements of the endoscopic imaging system are presented in tissue phantoms and in vivo mouse colon, verifying the endoscope's capabilities to accurately measure effective attenuation coefficient and differentiate diseased from normal colon.
• Watson, J. M., Marion, S. L., Rice, P. F., Bentley, D. L., Besselsen, D. G., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2014). In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis. CANCER BIOLOGY & THERAPY, 15(1), 42-60.
• Watson, J. M., Marion, S. L., Rice, P. F., Bentley, D. L., Besselsen, D. G., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2014). In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis. Cancer Biology and Therapy, 15(1), 42-60.
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  Abstract: Identification of the early microscopic changes associated with ovarian cancer may lead to development of a diagnostic test for high-risk women. In this study we use optical coherence tomography (OCT) and multiphoton microscopy (MPM) (collecting both two photon excited fluorescence [TPEF] and second harmonic generation [SH G]) to image mouse ovaries in vivo at multiple time points. We demonstrate the feasibility of imaging mouse ovaries in vivo during a longterm survival study and identify microscopic changes associated with early tumor development. These changes include alterations in tissue microstructure, as seen by OCT, alterations in cellular fluorescence and morphology, as seen by TPEF, and remodeling of collagen structure, as seen by SH G. These results suggest that a combined OCT-MPM system may be useful for early detection of ovarian cancer. © 2014 Landes Bioscience.
• Watson, J. M., Marion, S. L., Rice, P. F., Bentley, D. L., Besselsen, D. G., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2014). In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis. Cancer biology & therapy, 15(1), 42-60.
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  Identification of the early microscopic changes associated with ovarian cancer may lead to development of a diagnostic test for high-risk women. In this study we use optical coherence tomography (OCT) and multiphoton microscopy (MPM) (collecting both two photon excited fluorescence [TPEF] and second harmonic generation [SHG]) to image mouse ovaries in vivo at multiple time points. We demonstrate the feasibility of imaging mouse ovaries in vivo during a long-term survival study and identify microscopic changes associated with early tumor development. These changes include alterations in tissue microstructure, as seen by OCT, alterations in cellular fluorescence and morphology, as seen by TPEF, and remodeling of collagen structure, as seen by SHG. These results suggest that a combined OCT-MPM system may be useful for early detection of ovarian cancer.
• Welge, W. A., DeMarco, A. T., Watson, J. M., Rice, P. S., Barton, J. K., & Kupinski, M. A. (2014). Diagnostic potential of multimodal imaging of ovarian tissue using optical coherence tomography and second-harmonic generation microscopy. Journal of medical imaging (Bellingham, Wash.), 1(2), 025501.
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  Ovarian cancer is particularly deadly because it is usually diagnosed after it has metastasized. We have previously identified features of ovarian cancer using optical coherence tomography (OCT) and second-harmonic generation (SHG) microscopy (targeting collagen). OCT provides an image of the ovarian microstructure while SHG provides a high-resolution map of collagen fiber bundle arrangement. Here we investigated the diagnostic potential of dual-modality OCT and SHG imaging. We conducted a fully crossed, multi-reader, multi-case study using seven human observers. Each observer classified 44 ex vivo mouse ovaries (16 normal and 28 abnormal) as normal or abnormal from OCT, SHG, and simultaneously viewed, co-registered OCT and SHG images and provided a confidence rating on a six-point scale. We determined the average receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and other quantitative figures of merit. The results show that OCT has diagnostic potential with an average AUC of 0.91 ± 0.06. The average AUC for SHG was less promising at 0.71 ± 0.13. The average AUC for simultaneous OCT and SHG was not significantly different from OCT alone, possibly due to the limited SHG field of view. The high performance of OCT and co-registered OCT and SHG warrants further investigation.
• Welge, W. A., DeMarco, A. T., Watson, J. M., Rice, P. S., Barton, J. K., & Kupinski, M. A. (2014). Objective assessment of multimodality optical coherence tomography and second-harmonic generation image quality of ex vivo mouse ovaries using human observers. DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES VII, 8936.
• Barton, J. K., Barton, J. K., Marion, S. L., Rice, P. F., Utzinger, U., Brewer, M. A., Hoyer, P. B., & Barton, J. K. (2013). Two-photon excited fluorescence imaging of endogenous contrast in a mouse model of ovarian cancer. Lasers in surgery and medicine, 45(3).
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  Ovarian cancer has an extremely high mortality rate resulting from poor understanding of the disease. In order to aid understanding of disease etiology and progression, we identify the endogenous fluorophores present in a mouse model of ovarian cancer and describe changes in fluorophore abundance and distribution with age and disease.
• Barton, J., Bonnema, G. T., Cardinal, K. O., McNally, J. B., Williams, S. K., & Barton, J. K. (0). Assessment of blood vessel mimics with optical coherence tomography. Journal of biomedical optics, 12(2).
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  Optical coherence tomography (OCT) is an imaging modality that enables assessment of tissue structural characteristics. Studies have indicated that OCT is a useful method to assess both blood vessel morphology and the response of a vessel to a deployed stent. We evaluated the ability of OCT to visualize the cellular lining of a tissue-engineered blood vessel mimic (BVM) and the response of this lining to a bare metal stent. We develop a side-firing endoscope that obtains intraluminal, longitudinal scans within the sterile bioreactor environment, enabling time-serial assessment. Seventeen BVMs are imaged with the endoscopic OCT system. The BVMs are then evaluated via fluorescence microscopy and/or standard histologic techniques. We determine that (1) the OCT endoscope can be repeatedly inserted without visible damage to the BVM cellular lining, (2) OCT provides a precise measure of cellular lining thickness with good correlation to measurements obtained from histological sections, and (3) OCT is capable of monitoring the accumulation of cellular material in response to a metallic stent. Our studies indicate that OCT is a useful technique for monitoring the BVM cellular lining, and that OCT may facilitate the use of BVMs for early stage device assessment.
• Barton, J., Davidson, B. R., & Barton, J. K. (0). Application of optical coherence tomography to automated contact lens metrology. Journal of biomedical optics, 15(1).
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  Optical coherence tomography (OCT) is a nondestructive imaging modality with the potential to make quantitative spatial measurements. OCT's noncontact nature, sensitivity to small refractive index mismatches, and micron-scale resolution make it attractive for contact lens metrology, specifically, measuring prism. Prism is defined as the maximum difference in thickness of the contact lens, measured over a full 360 deg of rotation, at a fixed distance from the contact lens edge. We develop and test a novel algorithm that automatically analyzes OCT images and calculates prism. Images are obtained using a Thorlabs OCT930SR OCT system. The OCT probe is fastened to an automated rotation stage that rotates 360 deg in small increments (typically 10 deg) to acquire OCT images of the edge of the contact lens around the entire circumference. The images are 1.6 mm in optical depth (512 pixels) and 2 mm wide (1000 pixels). Several sets of images are successfully analyzed. The prism measured for a toric lens is 42 microm, which is in line with design parameters. Thickness measurements are repeatable with a standard deviation of 0.5 microm and maximum range of 1.8 microm over ten image sets. This work demonstrates the possibility of using OCT to perform nondestructive contact lens metrology.
• Barton, J., Kanter, E. M., Walker, R. M., Marion, S. L., Brewer, M., Hoyer, P. B., & Barton, J. K. (0). Dual modality imaging of a novel rat model of ovarian carcinogenesis. Journal of biomedical optics, 11(4).
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  Ovarian cancer is the fifth leading cause of cancer death in women, in part because of the limited knowledge about early stage disease. We develop a novel rat model of ovarian cancer and perform a pilot study to examine the harvested ovaries with complementary optical imaging modalities. Rats are exposed to repeated daily dosing (20 days) with 4-vinylcyclohexene diepoxide (VCD) to cause early ovarian failure (model for postmenopause), and ovaries are directly exposed to 7,12-dimethylbenz(a)anthracene (DMBA) to cause abnormal ovarian proliferation and neoplasia. Harvested ovaries are examined with optical coherence tomography (OCT) and light-induced fluorescence (LIF) at one, three, and five months post-DMBA treatment. VCD causes complete ovarian follicle depletion within 8 months after onset of dosing. DMBA induces abnormal size, cysts, and neoplastic changes. OCT successfully visualizes normal and abnormal structures (e.g., cysts, bursa, follicular remnant degeneration) and the LIF spectra show statistically significant changes in the ratio of average emission intensity at 390:450 nm between VCD-treated ovaries and both normal cycling and neoplastic DMBA-treated ovaries. Overall, this pilot study demonstrates the feasibility of both the novel animal model for ovarian cancer and the ability of optical imaging techniques to visualize ovarian function and health.
• Barton, J., Winkler, A. M., Rice, P. F., Drezek, R. A., & Barton, J. K. (0). Quantitative tool for rapid disease mapping using optical coherence tomography images of azoxymethane-treated mouse colon. Journal of biomedical optics, 15(4).
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  Optical coherence tomography (OCT) can provide new insight into disease progression and therapy by enabling nondestructive, serial imaging of in vivo cancer models. In previous studies, we have shown the utility of endoscopic OCT for identifying adenomas in the azoxymethane-treated mouse model of colorectal cancer and tracking disease progression over time. Because of improved imaging speed made possible through Fourier domain imaging, three-dimensional imaging of the entire mouse colon is possible. Increased amounts of data can facilitate more accurate classification of tissue but require more time on the part of the researcher to sift through and identify relevant data. We present quantitative software for automatically identifying potentially diseased areas that can be used to create a two-dimensional "disease map" from a three-dimensional Fourier domain OCT data set. In addition to sensing inherent changes in tissue that occur during disease development, the algorithm is sensitive to exogeneous highly scattering gold nanoshells that can be targeted to disease biomarkers. The results of the algorithm were compared to histological diagnosis. The algorithm was then used to assess the ability of gold nanoshells targeted to epidermal growth factor receptor in vivo to enable functional OCT imaging.
• Keenan, M., Leung, S., Rice, F., Wall, R. A., & Barton, J. K. (2013). Fluorescence-based SMC and OCT endoscope to study aberrant crypt foci in the mouse colon. ENDOSCOPIC MICROSCOPY VIII, 8575.
• Marion, S. L., Watson, J., Sen, N., Brewer, M. A., Barton, J. K., & Hoyer, P. B. (2013). 7,12-dimethylbenz[a]anthracene-induced malignancies in a mouse model of menopause. Comparative medicine, 63(1), 6-12.
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  Ovarian cancer has a high mortality rate because there are few symptoms in early disease development. The incidence of ovarian cancer increases in women after menopause. Understanding early events in this disease can best be achieved by using animal models. Therefore, the objective of this study was to develop and track the onset of ovarian tumorigenesis in mice mimicking characteristics of postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d) received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause ovarian failure. Four months after VCD treatment, via surgical intervention, each mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian neoplasms. The experimental groups were untreated controls (Con-Con), DMBA-treatment only (Con-DMBA), VCD treatment only (VCD-Con), and VCD+DMBA-treated (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were collected for histologic and immunohistochemical evaluation. No tumors developed in Con-Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5 mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were epithelial in origin. Our findings confirm that inducing ovarian tumors in mice by chemical means is an effective method for studying early stages of tumor development that may be relevant to epithelial ovarian cancers that arise in postmenopausal women.
• Watson, J. M., Marion, S. L., Rice, P. F., Bentley, D. L., Besselsen, D., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2013). In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia. OPTICAL BIOPSY XI, 8577.
• Welge, W. A., & Barton, J. K. (2013). Spiral-scanning, side-viewing optical coherence tomography endoscope for three-dimensional fully sampled in vivo imaging of the mouse colon. ENDOSCOPIC MICROSCOPY VIII, 8575.
• Barton, J. K., Barton, J. K., Rice, P. F., Marion, S. L., Brewer, M. A., Davis, J. R., Rodriguez, J. J., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2012). Analysis of second-harmonic-generation microscopy in a mouse model of ovarian carcinoma. Journal of biomedical optics, 17(7).
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  Second-harmonic-generation (SHG) imaging of mouse ovaries ex vivo was used to detect collagen structure changes accompanying ovarian cancer development. Dosing with 4-vinylcyclohexene diepoxide and 7,12-dimethylbenz[a]anthracene resulted in histologically confirmed cases of normal, benign abnormality, dysplasia, and carcinoma. Parameters for each SHG image were calculated using the Fourier transform matrix and gray-level co-occurrence matrix (GLCM). Cancer versus normal and cancer versus all other diagnoses showed the greatest separation using the parameters derived from power in the highest-frequency region and GLCM energy. Mixed effects models showed that these parameters were significantly different between cancer and normal (P
• Barton, J., Wall, R. A., & Barton, J. K. (2012). Fluorescence-based surface magnifying chromoendoscopy and optical coherence tomography endoscope. Journal of biomedical optics, 17(8).
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  A side-viewing, 2.3-mm diameter, surface magnifying chromoendoscopy-optical coherence tomography (SMC-OCT) endoscope has been designed for simultaneous, nondestructive surface fluorescence visualization and cross-sectional imaging. We apply this endoscope to in vivo examination of the mouse colon. A 30,000 element fiber bundle is combined with single mode fibers, for SMC and OCT imaging, respectively. The distal optics consist of a gradient-index lens and spacer to provide a 1× magnification at a working distance of 1.58 mm in air, necessary to image the sample through a 0.23-mm thick outer glass envelope, and an aluminized right-angle prism fixed to the distal end of the gradient-index lens assembly. The resulting 1∶1 imaging system is capable of 3.9-µm lateral and 2.3-µm axial resolution in the OCT channel, and 125-lp/mm resolution across a 0.70-mm field of view in the SMC channel. The endoscope can perform high contrast crypt visualization, molecular imaging, and cross-sectional imaging of colon microstructure.
• LeGendre-McGhee, S., Rice, P., Wall, R. A., Klein, J., Luttman, A., Sprute, K., Gerner, E., & Barton, J. K. (2012). Endoscopic spectral domain optical coherence tomography of murine colonic morphology to determine effectiveness of chemopreventive and chemotherapeutic agents in colorectal cancer. ENDOSCOPIC MICROSCOPY VII, 8217.
• Wall, R. A., & Barton, J. K. (2012). Fluorescence-based surface magnifying chromoendoscopy and optical coherence tomography endoscope. ENDOSCOPIC MICROSCOPY VII, 8217.
• Watson, J. M., Rice, P. F., Marion, S. L., Brewer, M. A., Davis, J. R., Rodriguez, J. J., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2012). Analysis of Second-Harmonic Generation Microscopy in a Mouse Model of Ovarian Carcinoma. Journal of Biomedical Optics, 17(7), 076002-1 to 076002-9.
• Yang, M., Winkler, A., Klein, J., & Barton, J. K. (2012). Using optical coherence tomography to characterize thick-glaze structure: Chinese Southern Song Guan glaze case study. Studies in Conservation, 57(2), 67-75.
• Barton, J., Korde, V. R., Liebmann, E., & Barton, J. K. (2011). Design of a handheld optical coherence microscopy endoscope. Journal of biomedical optics, 16(6).
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  Optical coherence microscopy (OCM) combines coherence gating, high numerical aperture optics, and a fiber-core pinhole to provide high axial and lateral resolution with relatively large depth of imaging. We present a handheld rigid OCM endoscope designed for small animal surgical imaging, with a 6-mm diam tip, 1-mm scan width, and 1-mm imaging depth. X-Y scanning is performed distally with mirrors mounted to micro galvonometer scanners incorporated into the endoscope handle. The endoscope optical design consists of scanning doublets, an afocal Hopkins relay lens system, a 0.4 numerical aperture water immersion objective, and a cover glass. This endoscope can resolve laterally a 1.4-μm line pair feature and has an axial resolution (full width half maximum) of 5.4 μm. Images taken with this endoscope of fresh ex-vivo mouse ovaries show structural features, such as corpus luteum, primary follicles, growing follicles, and fallopian tubes. This rigid handheld OCM endoscope can be useful for a variety of minimally invasive and surgical imaging applications.
• Barton, J., Winkler, A. M., Bonnema, G. T., & Barton, J. K. (2011). Optical polarimetry for noninvasive glucose sensing enabled by Sagnac interferometry. Applied optics, 50(17).
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  Optical polarimetry is used in pharmaceutical drug testing and quality control for saccharide-containing products (juice, honey). More recently, it has been proposed as a method for noninvasive glucose sensing for diabetic patients. Sagnac interferometry is commonly used in optical gyroscopes, measuring minute Doppler shifts resulting from mechanical rotation. In this work, we demonstrate that Sagnac interferometers are also sensitive to optical rotation, or the rotation of linearly polarized light, and are therefore useful in optical polarimetry. Results from simulation and experiment show that Sagnac interferometers are advantageous in optical polarimetry as they are insensitive to net linear birefringence and alignment of polarization components.
• Castro, J. M., Brownlee, J., Luo, Y., de Leon, E., Barton, J. K., Barbastathis, G., & Kostuk, R. K. (2011). Spatial-spectral volume holographic systems: resolution dependence on effective thickness. Applied optics, 50(7), 1038-46.
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  The resolution dependence of spatial-spectral volume holographic imaging systems on angular and spectral bandwidth of nonuniform gratings is investigated. Modeling techniques include a combination of the approximate coupled-wave analysis and the transfer-matrix method for holograms recorded in absorptive media. The effective thickness of the holograms is used as an estimator of the resolution of the imaging systems. The methodology, which assists in the design and optimization of volume holographic simulation results based on our approach, are confirmed with experiments and show proof of consistency and usefulness of the proposed models.
• Castro, J. M., Gelsinger-Austin, P. J., Barton, J. K., & Kostuk, R. K. (2011). Confocal-rainbow volume holographic imaging system. Applied optics, 50(10), 1382-8.
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  The performance of broadband volume holographic imaging system in terms of depth selectivity is investigated. The mechanism for depth resolution degradation is explained. In order to overcome this resolution degradation, a novel imaging device, the confocal-rainbow volume holographic imaging system, is proposed. Modeling and experimental validation of the performance of this novel imaging system indicates that depth resolution
• Castro, J. M., de Leon, E., Barton, J. K., & Kostuk, R. K. (2011). Analysis of diffracted image patterns from volume holographic imaging systems and applications to image processing. Applied optics, 50(2), 170-6.
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  Diffracted image patterns from volume holograms that are used in volume holographic imaging systems (VHISs) are investigated. It is shown that, in VHISs, prior information about the shape and spectral properties of the diffracted patterns is important not only to determine the curvature and field of view of the image, but also for image registration and noise removal. A new methodology to study numerically and analytically the dependence of VHIS diffraction patterns with the hologram construction parameters and the readout wavelength is described. Modeling and experimental results demonstrate that, in most cases, VHIS diffracted shapes can be accurately represented by hyperbolas.
• Kieu, K. Q., Klein, J., Evans, A., Barton, J. K., & Peyghambarian, N. (2011). Ultrahigh resolution all-reflective optical coherence tomography system with a compact fiber-based supercontinuum source. Journal of biomedical optics, 16(10), 106004.
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  We report the construction and characterization of an all-reflective optical coherence tomography (OCT) system using a newly developed compact fiber-based broadband supercontinuum source. The use of only reflective optical components has enabled us to avoid chromatic dispersion effects and to obtain ultrahigh resolution OCT images of biological samples. We achieved an axial resolution of 2 μm in air with 87 dB dynamic range at a center wavelength around 1300 nm.
• Kostuk, R. K., Barton, J. K., Luo, Y., Castro, J. M., & Barbastathis, G. (2011). Volume Holographic Spectral-Spatial Imaging of Biological Tissue. TRIBUTE TO JOSEPH W. GOODMAN, 8122.
• Linehan, J. A., Bracamonte, E. R., Hariri, L. P., Sokoloff, M. H., Rice, P. S., Barton, J. K., & Nguyen, M. M. (2011). Feasibility of optical coherence tomography imaging to characterize renal neoplasms: limitations in resolution and depth of penetration. BJU international, 108(11), 1820-4.
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  What's known on the subject? and What does the study add? Optical coherence tomography has been used for the diagnosis of retinal disease and has been used experimentally for imaging of vascular plaques, gastrointestinal pathology, bladder cancer, prostate cancer, and recently to examine benign kidney microanatomy. It has not been previously used to image kidney cancer. This study presents the first data on the utility of OCT in the imaging for renal neoplasms. It found that OCT was most successful in distinguishing AML and TCC from normal parenchyma. OCT had more limited success at differentiating oncocytoma. Clear cell tumors and other renal cancer subtypes had a more heterogenous appearance, precluding reliable identification using OCT. The study shows that higher resolution versions of OCT, such as OCM, will be needed to allow optical coherence imaging to reach clinical utility in the assessment of renal neoplasms.
• Luo, Y., de, L. E., Castro, J., Lee, J., Barton, J. K., Kostuk, R. K., & Barbastathis, G. (2011). Phase-contrast volume holographic imaging system. OPTICS LETTERS, 36(7), 1290-1292.
• Wall, R. A., Bonnema, G. T., & Barton, J. K. (2011). Novel focused OCT-LIF endoscope. BIOMEDICAL OPTICS EXPRESS, 2(3), 421-430.
• Watson, J. M., Rice, P. F., Marion, S. L., Bentley, D. L., Brewer, M. A., Utzinger, U., Hoyer, P. B., & Barton, J. K. (2011). Multi-modality optical imaging of ovarian cancer in post-menopausal mouse model. ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS IX, 7890.
• Winkler, A. M., Rice, P. F., Weichsel, J., Watson, J. M., Backer, M. V., Backer, J. M., & Barton, J. K. (2011). In vivo, dual-modality OCT/LIF imaging using a novel VEGF receptor-targeted NIR fluorescent probe in the AOM-treated mouse model. Molecular imaging and biology, 13(6), 1173-82.
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  Increased vascular endothelial growth factor (VEGF) receptor expression has been found at the sites of angiogenesis, particularly in tumor growth areas, as compared with quiescent vasculature. An increase in VEGF receptor-2 is associated with colon cancer progression. The in vivo detection of VEGF receptor is of interest for the purposes of studying basic mechanisms of carcinogenesis, making clinical diagnoses, and monitoring the efficacy of chemopreventive and therapeutic agents. In this study, a novel single chain (sc)VEGF-based molecular probe is utilized in the azoxymethane (AOM)-treated mouse model of colorectal cancer to study delivery route and specificity for disease.
• Winkler, A. M., Rice, P., Weichsel, J., Watson, J. M., Backer, M. V., Backer, J. M., & Barton, J. K. (2011). In Vivo, Dual-Modality OCT/LIF Imaging Using a Novel VEGF Receptor-Targeted NIR Fluorescent Probe in the AOM-Treated Mouse Model. MOLECULAR IMAGING AND BIOLOGY, 13(6), 1173-1182.
• Barton, J., Hariri, L. P., Liebmann, E. R., Marion, S. L., Hoyer, P. B., Davis, J. R., Brewer, M. A., & Barton, J. K. (2010). Simultaneous optical coherence tomography and laser induced fluorescence imaging in rat model of ovarian carcinogenesis. Cancer biology & therapy, 10(5).
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  Determining if an ovarian mass is benign or malignant is an ongoing clinical challenge. The development of reliable animal models provides means to evaluate new diagnostic tools to more accurately determine if an ovary has benign or malignant features. Although sex cord-stromal tumors (SCST) account for 0.1–0.5% of ovarian malignancies, they have similar appearances to more aggressive epithelial cancers and can serve as a prototype for developing better diagnostic methods for ovarian cancer. Optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy are non-destructive optical imaging modalities. OCT provides architectural cross-sectional images at near histological resolutions and LIF provides biochemical information. We utilize combined OCT-LIF to image ovaries in post-menopausal ovarian carcinogenesis rat models, evaluating normal cyclic, acyclic and neoplastic ovaries. Eighty-three female Fisher rats were exposed to combinations of control sesame oil, 4-vinyl cyclohexene diepoxide (VCD) to induce ovarian failure,and/or 7,12-dimethylbenz[a]anthracene (DMBA) to induce carcinogenesis. Three or five months post-treatment, 162 ovaries were harvested and imaged with OCT-LIF: 40 cyclic, 105 acyclic and 17 SCST. OCT identified various follicle stages,corpora lutea (CL), CL remnants, epithelial invaginations/inclusions and allowed for characterization of both cystic and solid SCST. Signal attenuation comparisons between CL and solid SCST revealed statistically significant increases in attenuation among CL. LIF characterized spectral differences in cyclic, acyclic and neoplastic ovaries attributed to collagen, NADH/FAD and hemoglobin absorption. We present combined OCT-LIF imaging in a rat ovarian carcinogenesis model, providing preliminary criteria for normal cyclic, acyclic and SCST ovaries which support the potential of OCT-LIF for ovarian imaging.
• Craig, Z. R., Davis, J. R., Marion, S. L., Barton, J. K., & Hoyer, P. B. (2010). 7,12-Dimethylbenz[A]Anthracene Induces Sertoli-Leydig-Cell Tumors in the Follicle-Depleted Ovaries of Mice Treated with 4-Vinylcyclohexene Diepoxide. COMPARATIVE MEDICINE, 60(1), 10-17.
• Gelsinger-Austin, P. J., Luo, Y., Watson, J. M., Kostuk, R. K., Barbastathis, G., Barton, J. K., & Castro, J. M. (2010). Optical Design for a Spatial-Spectral Volume Holographic Imaging System. Optical engineering (Redondo Beach, Calif.), 49(4), 43001.
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  Spatial Spectral Holographic imaging system (S(2)-VHIS) is a promising alternative to confocal microscopy due to its capabilities to simultaneously image several sample depths with high resolution. However, the field of view of previously presented S(2)-VHIS prototypes has been restricted to less than 200μm. This paper presents experimental results of an improved S(2)-VHIS design which have a field of view of ~1mm while maintaining high resolution and dynamic range.
• Gelsinger-Austin, P. J., Luo, Y., Watson, J. M., Kostuk, R. K., Barbastathis, G., Barton, J. K., & Castro, J. M. (2010). Optical design for a spatial-spectral volume holographic imaging system. OPTICAL ENGINEERING, 49(4).
• Luo, Y., Castro, J., Barton, J. K., Kostuk, R. K., & Barbastathis, G. (2010). Simulations and experiments of aperiodic and multiplexed gratings in volume holographic imaging systems. OPTICS EXPRESS, 18(18), 19273-19285.
• Wall, R. A., Bonnema, G. T., & Barton, J. K. (2010). Focused OCT and LIF Endoscope. ENDOSCOPIC MICROSCOPY V, 7558.
• Winkler, A. M., Bonnema, G. T., & Barton, J. K. (2010). New Scheme for Polarimetric Glucose Sensing without Polarizers. OPTICAL DIAGNOSTICS AND SENSING X: TOWARD POINT-OF-CARE DIAGNOSTICS, 7572.
• Barton, J., Hariri, L. P., Bonnema, G. T., Schmidt, K., Winkler, A. M., Korde, V., Hatch, K. D., Davis, J. R., Brewer, M. A., & Barton, J. K. (2009). Laparoscopic optical coherence tomography imaging of human ovarian cancer. Gynecologic oncology, 114(2).
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  Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo.
• Bonnema, G. T., Cardinal, K. O., Williams, S. K., & Barton, J. K. (2009). A concentric three element radial scanning optical coherence tomography endoscope. JOURNAL OF BIOPHOTONICS, 2(6-7), 353-356.
• Davidson, B. R., & Barton, J. K. (2009). Automated contact lens measurement using optical coherence tomography. ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS VII, 7169.
• Hariri, L. P., Bonnema, G. T., Schmidt, K., Korde, V., Winkler, A. M., Hatch, K., Brewer, M., & Barton, J. K. (2009). Laparoscopic optical coherence tomographic imaging of human ovarian cancer. ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS VII, 7169.
• Hoyer, P. B., Davis, J. R., Bedrnicek, J. B., Marion, S. L., Christian, P. J., Barton, J. K., & Brewer, M. A. (2009). Ovarian neoplasm development by 7,12-dimethylbenz[a]anthracene (DMBA) in a chemically-induced rat model of ovarian failure. Gynecologic oncology, 112(3), 610-5.
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  The objectives were to determine the time course for ovarian failure in rats caused by 4-vinylcyclohexene diepoxide (VCD) and develop a model for ovarian cancer in which ovarian neoplasms were chemically induced in an animal that was follicle depleted, but retained residual ovarian tissue.
• Korde, V. R., Bartels, H., Barton, J., & Ranger-Moore, J. (2009). Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis. Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 31(2), 83-9.
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  To automatically segment cell nuclei in histology images of bladder and skin tissue for karyometric analysis.
• Korde, V. R., Liebmann, E., & Barton, J. K. (2009). Design of a Handheld Optical Coherence Microscopy Endoscope. ENDOSCOPIC MICROSCOPY IV, 7172.
• Winkler, A. M., Rice, P., Weichsel, J., Backer, M. V., Backer, J. M., & Barton, J. K. (2009). In vivo imaging using a VEGF-based near-infrared fluorescent probe for early cancer diagnosis in the AOM-treated mouse model. REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS, 7190.
• Zhang, Y., Davidson, B. R., Stamer, W. D., Barton, J. K., Marmorstein, L. Y., & Marmorstein, A. D. (2009). Enhanced inflow and outflow rates despite lower IOP in bestrophin-2-deficient mice. Investigative ophthalmology & visual science, 50(2), 765-70.
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  Bestrophin-2 (Best2), a putative Cl(-) channel is expressed in the nonpigmented epithelium (NPE). Disruption of Best2 in mice results in a diminished intraocular pressure (IOP). Aqueous humor dynamics were compared in Best2(+/+) and Best2(-/-) mice, to better understand the contribution of Best2 to IOP.
• Arauz, L. J., Luo, Y., Castillo, J. E., Barton, J., & Kostuk, R. K. (2008). Fiber array fabrication technique for 15-mu m-diameter single-mode fibers. OPTICAL ENGINEERING, 47(7).
• Barton, J., Bonnema, G. T., Cardinal, K. O., Williams, S. K., & Barton, J. K. (2008). An automatic algorithm for detecting stent endothelialization from volumetric optical coherence tomography datasets. Physics in medicine and biology, 53(12).
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  Recent research has suggested that endothelialization of vascular stents is crucial to reducing the risk of late stent thrombosis. With a resolution of approximately 10 microm, optical coherence tomography (OCT) may be an appropriate imaging modality for visualizing the vascular response to a stent and measuring the percentage of struts covered with an anti-thrombogenic cellular lining. We developed an image analysis program to locate covered and uncovered stent struts in OCT images of tissue-engineered blood vessels. The struts were found by exploiting the highly reflective and shadowing characteristics of the metallic stent material. Coverage was evaluated by comparing the luminal surface with the depth of the strut reflection. Strut coverage calculations were compared to manual assessment of OCT images and epi-fluorescence analysis of the stented grafts. Based on the manual assessment, the strut identification algorithm operated with a sensitivity of 93% and a specificity of 99%. The strut coverage algorithm was 81% sensitive and 96% specific. The present study indicates that the program can automatically determine percent cellular coverage from volumetric OCT datasets of blood vessel mimics. The program could potentially be extended to assessments of stent endothelialization in native stented arteries.
• Barton, J., Tumlinson, A. R., Hofer, B., Winkler, A. M., Povazay, B., Drexler, W., & Barton, J. K. (2008). Inherent homogenous media dispersion compensation in frequency domain optical coherence tomography by accurate k-sampling. Applied optics, 47(5).
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  Depth dependent broadening of the axial point spread function due to dispersion in the imaged media, and algorithms for postprocess correction, have been previously described for both time domain and frequency domain optical coherence tomography. We show that homogeneous media dispersion artifacts disappear when frequency domain samples are acquired with uniform spacing in circular wavenumber, as opposed to uniform sampling in optical frequency. We further explicate the source of this point spread broadening and simulate its magnitude in aqueous media. We experimentally demonstrate media dispersion compensation in high dispersion glass by choosing sample frequencies at equal intervals of media index of refraction divided by vacuum wavelength, and we recover unbroadened reflections without an additional postprocessing step.
• Bonnema, G. T., Cardinal, K. O., Williams, S. K., & Barton, J. K. (2008). Imaging stented tissue engineered blood vessel mimics. OPTICS IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE II, 6858.
• Hariri, L. P., Bonnema, G. T., Schmidt, K., Hatch, K., Brewer, M., & Barton, J. K. (2008). Laparoscopic optical coherence tomographic imaging of human ovarian cancer. ENDOSCOPIC MICROSCOPY III, 6851, U21-U27.
• Luo, Y., Gelsinger, P. J., Barton, J. K., Barbastathis, G., & Kostuk, R. K. (2008). Multiplexing volume holographic gratings for a spectral-spatial imaging system. PRACTICAL HOLOGRAPHY XXII: MATERIALS AND APPLICATIONS, 6912.
• Luo, Y., Gelsinger, P. J., Barton, J. K., Barbastathis, G., & Kostuk, R. K. (2008). Optimization of multiplexed holographic gratings in PQ-PMMA for spectral-spatial imaging filters. Optics letters, 33(6), 566-8.
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  Holographic gratings formed in thick phenanthrenquinone- (PQ-) doped poly(methyl methacrylate) (PMMA) can be made to have narrowband spectral and spatial transmittance filtering properties. We present the design and performance of angle-multiplexed holographic filters formed in PQ-PMMA at 488 nm and reconstructed with a LED operated at approximately 630 nm. The dark delay time between exposure and the preillumination exposure of the polymer prior to exposure of the holographic area are varied to optimize the diffraction efficiency of multiplexed holographic filters. The resultant holographic filters can enhance the performance of four-dimensional spatial-spectral imaging systems. The optimized filters are used to simultaneously sample spatial and spectral information at five different depths separated by 50 microm within biological tissue samples.
• Luo, Y., Gelsinger-Austin, P. J., Watson, J. M., Barbastathis, G., Barton, J. K., & Kostuk, R. K. (2008). Laser-induced fluorescence imaging of subsurface tissue structures with a volume holographic spatial-spectral imaging system. Optics letters, 33(18), 2098-100.
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  A three-dimensional imaging system incorporating multiplexed holographic gratings to visualize fluorescence tissue structures is presented. Holographic gratings formed in volume recording materials such as a phenanthrenquinone poly(methyl methacrylate) photopolymer have narrowband angular and spectral transmittance filtering properties that enable obtaining spatial-spectral information within an object. We demonstrate this imaging system's ability to obtain multiple depth-resolved fluorescence images simultaneously.
• Troutman, T. S., Barton, J. K., & Romanowski, M. (2008). Biodegradable plasmon resonant nanoshells. ADVANCED MATERIALS, 20(13), 2604-+.
• Tumlinson, A. R., Hariri, L. P., Drexler, W., & Barton, J. K. (2008). Scatter sensitive microscopic techniques to identify contrasting mucosal structures in ultrahigh-resolution optical coherence tomograms of mouse colon. ENDOSCOPIC MICROSCOPY III, 6851, U28-U39.
• Vargas, G., Barton, J. K., & Welch, A. J. (2008). Use of hyperosmotic chemical agent to improve the laser treatment of cutaneous vascular lesions. JOURNAL OF BIOMEDICAL OPTICS, 13(2).
• Winkler, A. M., Rice, P., Backer, J. M., Drezek, R. A., Romanowski, M., & Barton, J. K. (2008). Fluorescent and scattering contrast agents in a mouse model of colorectal cancer. LASERS IN SURGERY AND MEDICINE, 12-12.
• Barton, J. K. (2007). Biophotonics - Big images small features. NATURE PHOTONICS, 1(12), 683-685.
• Barton, J. K., Tang, S., Lim, R., & Tromberg, B. J. (2007). Optical coherence and multiphoton microscopy of skin-equivalent tissue models. LASERS IN SURGERY AND MEDICINE, 13-13.
• Barton, J. K., Tang, S., Lim, R., & Tromberg, B. J. (2007). Simultaneous optical coherence and multiphoton microscopy of skin-equivalent tissue models - art. no. 66270X. OPTICAL COHERENCE TOMOGRAPHY AND COHERENCE TECHNIQUES III, 6627, X6270-X6270.
• Barton, J., Hariri, L. P., Qiu, Z., Tumlinson, A. R., Besselsen, D. G., Gerner, E. W., Ignatenko, N. A., Povazay, B., Hermann, B., Sattmann, H., McNally, J., Unterhuber, A., Drexler, W., & Barton, J. K. (2007). Serial endoscopy in azoxymethane treated mice using ultra-high resolution optical coherence tomography. Cancer biology & therapy, 6(11).
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  Optical coherence tomography (OCT) is a minimally invasive, depth-resolved imaging tool that can be implemented in a small diameter endoscope for imaging mouse models of colorectal cancer (CRC). In this study, we utilized ultrahigh resolution (UHR) OCT to serially image the lower colon of azoxymethane (AOM) treated A/J mouse models of CRC in order to monitor the progression of neoplastic transformations and determine if OCT is capable of identifying early disease.
• Barton, J., Hariri, L. P., Tumlinson, A. R., Wade, N. H., Besselsen, D. G., Utzinger, U., Gerner, E. W., & Barton, J. K. (2007). Ex vivo optical coherence tomography and laser-induced fluorescence spectroscopy imaging of murine gastrointestinal tract. Comparative medicine, 57(2).
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  Optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy each have clinical potential in identifying human gastrointestinal (GI) pathologies, yet their diagnostic capability in mouse models is unknown. In this study, we combined the 2 modalities to survey the GI tract of a variety of mouse strains and ages and to sample dysplasias and inflammatory bowel disease (IBD) of the intestines. Segments (length, 2.5 cm) of duodenum and lower colon and the entire esophagus were imaged ex-vivo with combined OCT and LIE We evaluated 30 normal mice (A/J and 10- and 21-wk-old and retired breeder C57BL/6J) and 10 mice each of 2 strains modeling colon cancer and IBD (Apc(Min) and IL2-deficient mice, respectively). Histology was used to classify tissue regions as normal, Peyer patch, dysplasia, adenoma, or IBD. Features in corresponding OCT images were analyzed. Spectra from each category were averaged and compared via Student t tests. OCT provided structural information that led to identification of the imaging characteristics of healthy mouse GI. With histology as the 'gold standard,' we developed preliminary image criteria for early disease in the form of adenomas, dysplasias, and IBD. LIF characterized the endogenous fluorescence of mouse GI tract, with spectral features corresponding to collagen, NADH, and hemoglobin. In the IBD sample, LIF emission spectra displayed potentially diagnostic peaks at 635 and 670 nm, which we attributed to increased porphyrin production by bacteria associated with IBD. OCT and LIF appear to be useful and complementary modalities for ex vivo imaging of mouse GI tissues.
• Barton, J., Korde, V. R., Bonnema, G. T., Xu, W., Krishnamurthy, C., Ranger-Moore, J., Saboda, K., Slayton, L. D., Salasche, S. J., Warneke, J. A., Alberts, D. S., & Barton, J. K. (2007). Using optical coherence tomography to evaluate skin sun damage and precancer. Lasers in surgery and medicine, 39(9).
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  Optical coherence tomography (OCT) is a depth resolved imaging modality that may aid in identifying sun damaged skin and the precancerous condition actinic keratosis (AK).
• Bonnema, G. T., Cardinal, K. O., Williams, S. K., & Barton, J. K. (2007). Imaging stented blood vessel mimics with optical coherence tomography. LASERS IN SURGERY AND MEDICINE, 46-46.
• Hariri, L. P., Qiu, Z., Tumlinson, A. R., Besselsen, D. G., Gerner, E. W., Ignatenko, N., Povazay, B., Hermann, B., Sattmann, H., McNally, J., Angelika, U., Drexler, W., & Barton, J. K. (2007). Serial endoscopy in azoxymethane treated mice using ultra-high resolution optical coherence tomography - art. no. 643208. Endoscopic Microscopy II, 6432, 43208-43208.
• Korde, V. R., Bartels, H., Ranger-Moore, J., & Barton, J. (2007). Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis - art. no. 66330V. BIOPHOTONICS 2007: OPTICS IN LIFE SCIENCE, 6633, V6330-V6330.
• Korde, V., Zhao, D., Raghunand, N., Black, J. F., Gillies, R., & Barton, J. K. (2007). Using methemoglobin as a magnetic resonance imaging contrast agent. LASERS IN SURGERY AND MEDICINE, 3-3.
• Luo, Y., Arauz, L. J., Castillo, J. E., Barton, J. K., & Kostuk, R. K. (2007). Parallel optical coherence tomography system. Applied optics, 46(34), 8291-7.
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  We present the design and procedures for implementing a parallel optical coherence tomography (POCT) imaging system that can be adapted to an endoscopic format. The POCT system consists of a single mode fiber (SMF) array with multiple reduced diameter (15 microm) SMFs in the sample arm with 15 microm center spacing between fibers. The size of the array determines the size of the transverse imaging field. Electronic scanning eliminates the need for mechanically scanning in the lateral direction. Experimental image data obtained with this system show the capability for parallel axial scan acquisition with lateral resolution comparable to mechanically scanned optical coherence tomography systems.
• Luo, Y., Castillo, J., Arauz, L., Barton, J., & Kostuk, R. K. (2007). Coupling and cross-talk effects in 12-15 microm diameter single-mode fiber arrays for simultaneous transmission and photon collection from scattering media. Applied optics, 46(2), 253-61.
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  We examine signal degradation effects in fiber arrays from fiber-to-fiber coupling and from cross talk attributable to backscatter from the sample medium originating from adjacent fibers in the array. An analysis of coupling and cross talk for single-mode fibers (SMFs) operating at 1310 nm with different core diameters, interaction lengths, core center spacing, and numerical apertures (NAs) is evaluated. The coupling was evaluated using beam propagation algorithms and cross talk was analyzed by using Monte Carlo methods. Several multimode fiber types that are currently used in fiber image guides were also evaluated for comparative purposes. The analysis shows that an optimum NA and core diameter can be found for a specific fiber center separation that maximizes the directly backscattered signal relative to the cross talk. The coupling between fibers can be kept less than -35 dB for interaction lengths less than 5 mm. The calculations were compared to an experimentally fabricated SMF array with 15 microm center spacing and showed good agreement. The experimental fiber array without a lens was also used in a coherent detection configuration to measure the position of a mirror. Accurate depth ranging up to a distance of 250 microm from the tip of the fiber was achieved, which was five times the Rayleigh range of the beam emitted from the fiber.
• Troutman, T. S., Barton, J. K., & Romanowski, M. (2007). Optical coherence tomography with plasmon resonant nanorods of gold. Optics letters, 32(11), 1438-40.
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  We explored plasmon resonant nanorods of gold as a contrast agent for optical coherence tomography (OCT). Nanorod suspensions were generated through wet chemical synthesis and characterized with spectrophotometry, transmission electron microscopy, and OCT. Polyacrylamide-based phantoms were generated with appropriate scattering and anisotropy coefficients (30 cm(-1) and 0.89, respectively) to image distribution of the contrast agent in an environment similar to that of tissue. The observed signal was dependent on whether the plasmon resonance peak overlapped the source bandwidth of the OCT, confirming the resonant character of enhancement. Gold nanorods with plasmon resonance wavelengths overlapping the OCT source yielded a signal-to-background ratio of 4.5 dB, relative to the tissue phantom. Strategies for OCT imaging with nanorods are discussed.
• Agrawal, A., Huang, S., Lin, A., Lee, M., Barton, J. K., Drezek, R. A., & Pfefer, T. J. (2006). Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells. JOURNAL OF BIOMEDICAL OPTICS, 11(4).
• Barton, J., Gossage, K. W., Smith, C. M., Kanter, E. M., Hariri, L. P., Stone, A. L., Rodriguez, J. J., Williams, S. K., & Barton, J. K. (2006). Texture analysis of speckle in optical coherence tomography images of tissue phantoms. Physics in medicine and biology, 51(6).
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  Optical coherence tomography (OCT) is an imaging modality capable of acquiring cross-sectional images of tissue using back-reflected light. Conventional OCT images have a resolution of 10-15 microm, and are thus best suited for visualizing tissue layers and structures. OCT images of collagen (with and without endothelial cells) have no resolvable features and may appear to simply show an exponential decrease in intensity with depth. However, examination of these images reveals that they display a characteristic repetitive structure due to speckle. The purpose of this study is to evaluate the application of statistical and spectral texture analysis techniques for differentiating living and non-living tissue phantoms containing various sizes and distributions of scatterers based on speckle content in OCT images. Statistically significant differences between texture parameters and excellent classification rates were obtained when comparing various endothelial cell concentrations ranging from 0 cells/ml to 25 million cells/ml. Statistically significant results and excellent classification rates were also obtained using various sizes of microspheres with concentrations ranging from 0 microspheres/ml to 500 million microspheres/ml. This study has shown that texture analysis of OCT images may be capable of differentiating tissue phantoms containing various sizes and distributions of scatterers.
• Barton, J., Hariri, L. P., Tumlinson, A. R., Besselsen, D. G., Utzinger, U., Gerner, E. W., & Barton, J. K. (2006). Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model. Lasers in surgery and medicine, 38(4).
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  The diagnostic feasibility of optical coherence tomography (OCT) and laser-induced fluorescence (LIF) have been evaluated for human colorectal cancer. This study applies these technologies to a murine model of colorectal adenoma.
• Barton, J., McNally, J. B., Kirkpatrick, N. D., Hariri, L. P., Tumlinson, A. R., Besselsen, D. G., Gerner, E. W., Utzinger, U., & Barton, J. K. (2006). Task-based imaging of colon cancer in the Apc(Min/+) mouse model. Applied optics, 45(13).
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  Optical coherence tomography (OCT), laser-induced fluorescence (LIF), and laser-scanning confocal microscopy (LSCM) were used for the task of multimodal study of healthy and adenomatous mouse colon. The results from each modality were compared with histology, which served as the gold standard. The Apc(Min/+) genetic mouse model of colon cancer was compared with wild-type mice. In addition, a special diet was used for the task of studying the origins of a 680 nm autofluorescent signal that was previously observed in colon. The study found close agreement among each of the modalities and with histology. All four modalities were capable of identifying diseased tissue accurately. The OCT and LSCM images provided complementary structural information about the tissue, while the autofluorescence signal measured by LIF and LSCM provided biochemical information. OCT and LIF were performed in vivo and nondestructively, while the LSCM and histology required extraction of the tissue. The magnitude of the 680 nm signal correlates with chlorophyll content in the mouse diet, suggesting that the autofluorescent compound is a dietary metabolite.
• Cardinal, K. O., Bonnema, G. T., Hofer, H., Barton, J. K., & Williams, S. K. (2006). Tissue-engineered vascular grafts as in vitro blood vessel mimics for the evaluation of endothelialization of intravascular devices. Tissue engineering, 12(12), 3431-8.
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  The accelerating use of minimally invasive procedures for the treatment of cardiovascular disease, and the commensurate development of intravascular devices such as stents, has lead to a high demand for preclinical assessment techniques. A 3-dimensional in vitro blood vessel mimic (BVM) would be ideal for device testing before animal or clinical studies. This is possible based on current capabilities for the creation of tissue-engineered vascular grafts (TEVGs). Using an established method of pressure-sodding human endothelial cells onto a polymer scaffold, a BVM was created in an in vitro bioreactor system under flow. Scanning electron microscopy and immunohistochemistry verified a cellular lining and revealed a luminal monolayer of endothelial cells. After BVM development, bare metal stents were deployed. Stented and unstented BVMs were evaluated using fluorescent nuclear staining and optical coherence tomography (OCT). En face and cross-sectional evaluation of bisbenzimide-stained nuclei revealed cellular coverage of the stent surfaces. Cross-sectional evaluation using OCT also illustrated a cellular layer developing over the stent struts. These data support the use of TEVGs as in vitro BVMs for pre-clinical evaluation of the endothelial cell response to stents and endovascular devices.
• Lee, M., Nammalvar, V., Gobin, A., Barton, J., West, J., & Drezek, R. (2006). Nanoshells as contrast agents for scatter-based optical imaging. 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3, 371-+.
• Tumlinson, A. R., Povazay, B., Hariri, L. P., McNally, J., Unterhuber, A., Hermann, B., Sattmann, H., Drexler, W., & Barton, J. K. (2006). In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope. JOURNAL OF BIOMEDICAL OPTICS, 11(6).
• Alberding, J. P., Baldwin, A. L., Barton, J. K., & Wiley, E. (2005). Effects of pulsation frequency and endothelial integrity on enhanced arterial transmural filtration produced by pulsatile pressure. American journal of physiology. Heart and circulatory physiology, 289(2), H931-7.
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  The role of the endothelium in regulating transmural fluid filtration into the artery wall under pulsatile pressure and the effects of changes in pulsatile frequency on filtration have received little attention. Previous experiments (Alberding JP, Baldwin AL, Barton JK, and Wiley E. Am J Physiol Heart Circ Physiol 286: H1827-H1835, 2004) demonstrated significantly increased filtration after initial onset of pulsatile pressure compared with that predicted by using parameters measured under steady pressure. To determine the role of the endothelium in this phenomenon, the following experiments were performed on five New Zealand White rabbits (anesthetized with 30 mg/kg pentobarbital sodium). One of each pair of carotid arteries was deendothelialized, and filtration measurements under steady and pulsatile pressure were compared with those made in intact vessels (Alberding JP, Baldwin AL, Barton JK, and Wiley E. Am J Physiol Heart Circ Physiol 286: H1827-H1835, 2004). To determine the effect of increasing pulsatile frequency on arterial filtration, transmural filtration was measured by using pulsatile pressure frequencies of 1 Hz, followed by 2 Hz, in another set of intact arteries (6 arteries and 3 animals). For deendothelialized vessels, the initial increase in filtration after onset of pulsatility was similar to that observed in intact vessels, but the subsequent reduction in filtration was less abrupt. When pulsatile frequency was increased from 1 to 2 Hz in intact arteries, an initial increase in filtration was observed, similar to that obtained after onset of pulsatile pressure subsequent to a steady pressure. The observed responses of arteries to pulsatile pressure, with and without endothelium, or undergoing a frequency change, suggest a dynamic role for the endothelium in regulating transvascular transport in vivo.
• Barton, J., Kariya, R., Mathine, D. L., & Barton, J. K. (2004). Analog CMOS circuit design and characterization for optical coherence tomography signal processing. IEEE transactions on bio-medical engineering, 51(12).
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  We have developed a custom analog CMOS circuit to perform the signal processing for an optical coherence tomography imaging system. The circuit is realized in a 1.5 microm low-noise analog CMOS technology. The circuitry extracts the Doppler frequency from the signal and electrically mixes this with the original signal to provide a filtered A-scan. The circuitry was used to produce a two-dimensional image of an onion.
• Barton, J., Tumlinson, A. R., Hariri, L. P., Utzinger, U., & Barton, J. K. (2004). Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement. Applied optics, 43(1).
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  We have designed a multimodality system that combines optical coherence tomography (OCT) and laser-induced fluorescence (LIF) in a 2.0-mm-diameter endoscopic package. OCT provides approximately 18-microm resolution cross-sectional structural information over a 6-mm field. LIF spectra are collected sequentially at submillimeter resolution across the same field and provide histochemical information about the tissue. We present the use of a rod prism to reduce the asymmetry in the OCT beam caused by a cylindrical window. The endoscope has been applied to investigate mouse colon cancer in vivo.
• Barton, J., Gossage, K. W., Tkaczyk, T. S., Rodriguez, J. J., & Barton, J. K. (2003). Texture analysis of optical coherence tomography images: feasibility for tissue classification. Journal of biomedical optics, 8(3).
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  Optical coherence tomography (OCT) acquires cross-sectional images of tissue by measuring back-reflected light. Images from in vivo OCT systems typically have a resolution of 10 to 15 mm, and are thus best suited for visualizing structures in the range of tens to hundreds of microns, such as tissue layers or glands. Many normal and abnormal tissues lack visible structures in this size range, so it may appear that OCT is unsuitable for identification of these tissues. However, examination of structure-poor OCT images reveals that they frequently display a characteristic texture that is due to speckle. We evaluated the application of statistical and spectral texture analysis techniques for differentiating tissue types based on the structural and speckle content in OCT images. Excellent correct classification rates were obtained when images had slight visual differences (mouse skin and fat, correct classification rates of 98.5 and 97.3%, respectively), and reasonable rates were obtained with nearly identical-appearing images (normal versus abnormal mouse lung, correct classification rates of 64.0 and 88.6%, respectively). This study shows that texture analysis of OCT images may be capable of differentiating tissue types without reliance on visible structures.
• Barton, J., Hansen, K. A., Weiss, J. A., & Barton, J. K. (2002). Recruitment of tendon crimp with applied tensile strain. Journal of biomechanical engineering, 124(1).
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  The tensile stress-strain behavior of ligaments and tendons begins with a toe region that is believed to result from the straightening of crimped collagen fibrils. The in situ mechanical function is mostly confined to this toe region and changes in crimp morphology are believed to be associated with pathological conditions. A relatively new imaging technique, optical coherence tomography (OCT), provides a comparatively inexpensive method for nondestructive investigation of tissue ultrastructure with resolution on the order of 15 microm and the potential for use in a clinical setting. The objectives of this work were to assess the utility of OCT for visualizing crimp period, and to use OCT to determine how crimp period changed as a function of applied tensile strain in rat tail tendon fascicles. Fascicles from rat tail tendons were subjected to 0.5 percent strain increments up to 5 percent and imaged at each increment using OCT. A comparison between OCT images and optical microscopy images taken between crossed polarizing lenses showed a visual correspondence between features indicative of crimp pattern. Crimp pattern always disappeared completely before 3 percent axial strain was reached. Average crimp period increased as strain increased, but both elongation and shortening occurred within single crimp periods during the application of increasing strain to the fascicle.

Proceedings Publications

• Kiekens, K. C., Galvez, D., Romano, G., Cordova, R., & Barton, J. K. (2020). Falloposcope Modifications for Clinical Trials. In CLEO: Applications and Technology.
• Vega, D., & Barton, J. K. (2020). Using customized computational analyses to evaluate the feasibility and risk of endoscopes with an SNR analysis as an example (Conference Presentation). In Design and Quality for Biomedical Technologies XIII, 11231.
• Barton, J. K., Tate, T., & McGregor, D. (2017, February). Single lens system for forward-viewing navigation and scanning side-viewing optical coherence tomography. In SPIE Photonics West, Endoscopic Microscopy XII, Proc. SPIE 10040.
• Winkler, A. M., F., P., Troutman, T. S., Backer, M. V., Backer, J. M., Drezek, R. A., Romanowski, M., & Barton, J. K. (2008, January). Fluorescent and scattering contrast agents in a mouse model of colorectal cancer. In Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 6851.
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  Abstract: In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye..

Presentations

• Barton, J. K. (2016, June 9, 2016). Optical Imaging Falloposcope for Ovarian Cancer Detection. Point of Care Translational Research Network. Bethesda, MD: NIH.
• Barton, J. K. (2016, Nov 9). Validating a mouse model of ovarian cancer for early detection through imaging. Oncology Models Forum. Bethesda, MD: NIH/NCI.
• Keenan, M., Tate, T., Swan, E. J., Black, J. F., Utzinger, U., & Barton, J. K. (2015, Spring). Dual-modal optical imaging microendoscope for ovarian cancer detection. BIOS Photonics West. San Francisco.