Jennifer Kehlet Barton

Jennifer Kehlet Barton

Director, BIO5 Institute
Thomas R. Brown Distinguished Chair in Biomedical Engineering
Professor, Agricultural-Biosystems Engineering
Professor, Biomedical Engineering
Professor, Electrical and Computer Engineering
Professor, Medical Imaging
Professor, Optical Sciences
Professor, Cancer Biology - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-0314

Work Summary

I develop new optical imaging devices that can detect cancer at the earliest stage. Optics has the resolution and sensitivity to find these small, curable lesions, and we design the endoscope that provide access to organs inside the body. .

Research Interest

Jennifer Barton, Ph.D. is known for her development of miniature endoscopes that combine multiple optical imaging techniques, particularly optical coherence tomography and fluorescence spectroscopy. She evaluates the suitability of these endoscopic techniques for detecting early cancer development in patients and pre-clinical models. She has a particular interest in the early detection of ovarian cancer, the most deadly gynecological malignancy. Additionally, her research into light-tissue interaction and dynamic optical properties of blood laid the groundwork for a novel therapeutic laser to treat disorders of the skin’s blood vessels. She has published over 100 peer-reviewed journal papers in these research areas. She is currently Professor of Biomedical Engineering, Electrical and Computer Engineering, Optical Sciences, Agriculture-Biosystems Engineering, and Medical Imaging at the University of Arizona. She has served as department head of Biomedical Engineering, Associate Vice President for Research, and is currently Director of the BIO5 Institute, a collaborative research institute dedicated to solving complex biology-based problems affecting humanity. She is a fellow of SPIE – the International Optics Society, and a fellow of the American Institute for Medical and Biological Engineering. Keywords: bioimaging, biomedical optics, biomedical engineering, bioengineering, cancer, endoscopes

Publications

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.

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.

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.

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.

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.

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.

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).

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.

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.