Kang, D., Martinez, R. V., Whitesides, G. M., & Tearney, G. J. (2013). Miniature grating for spectrally-encoded endoscopy. Lab on a chip, 13(9), 1810-6.
Spectrally-encoded endoscopy (SEE) is an ultraminiature endoscopy technology that acquires high-definition images of internal organs through a sub-mm endoscopic probe. In SEE, a grating at the tip of the imaging optics diffracts the broadband light into multiple beams, where each beam with a distinctive wavelength is illuminated on a unique transverse location of the tissue. By encoding one transverse coordinate with the wavelength, SEE can image a line of the tissue at a time without using any beam scanning devices. This feature of the SEE technology allows the SEE probe to be miniaturized to sub-mm dimensions. While previous studies have shown that SEE has the potential to be utilized for various clinical imaging applications, the translation of SEE for medicine has been hampered by challenges in fabricating the miniature grating inherent to SEE probes. This paper describes a new fabrication method for SEE probes. The new method uses a soft lithographic approach to pattern a high-aspect-ratio grating at the tip of the miniature imaging optics. Using this technique, we have constructed a 500 μm-diameter SEE probe. The miniature grating at the tip of the probe had a measured diffraction efficiency of 75%. The new SEE probe was used to image a human finger and formalin fixed mouse embryos, demonstrating the capability of this device to visualize key anatomic features of tissues with high image contrast. In addition to providing high quality imaging SEE optics, the soft lithography method allows cost-effective and reliable fabrication of these miniature endoscopes, which will facilitate the clinical translation of SEE technology.
Freeman, E. E., Semeere, A., Osman, H., Peterson, G., Rajadhyaksha, M., Gonzalez, S., Martin, J. N., Anderson, R. R., Tearney, G. J., & Kang, D. (2018). Smartphone confocal microscopy for imaging cellular structures in human skin in vivo. Biomedical Optics Express.
Brachtel, E. F., Johnson, N. B., Huck, A. E., Rice-Stitt, T. L., Vangel, M. G., Smith, B. L., Tearney, G. J., & Kang, D. (2016). Spectrally encoded confocal microscopy for diagnosing breast cancer in excision and margin specimens. Laboratory investigation; a journal of technical methods and pathology, 96(4), 459-67.
A large percentage of breast cancer patients treated with breast conserving surgery need to undergo multiple surgeries due to positive margins found during post-operative margin assessment. Carcinomas could be removed completely during the initial surgery and additional surgery avoided if positive margins can be determined intraoperatively. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has a potential to rapidly image the entire surgical margin at subcellular resolution and accurately determine margin status intraoperatively. In this study, in order to test the feasibility of using SECM for intraoperative margin assessment, we have evaluated the diagnostic accuracy of SECM for detecting various types of breast cancers. Forty-six surgically removed breast specimens were imaged with an SECM system. Side-by-side comparison between SECM and histologic images showed that SECM images can visualize key histomorphologic patterns of normal/benign and malignant breast tissues. Small (500 μm × 500 μm) spatially registered SECM and histologic images (n=124 for each) were diagnosed independently by three pathologists with expertise in breast pathology. Diagnostic accuracy of SECM for determining malignant tissues was high, average sensitivity of 0.91, specificity of 0.93, positive predictive value of 0.95, and negative predictive value of 0.87. Intra-observer agreement and inter-observer agreement for SECM were also high, 0.87 and 0.84, respectively. Results from this study suggest that SECM may be developed into an intraoperative margin assessment tool for guiding breast cancer excisions.
Elmariah, S., Luo, T., Azimi, E., Ordovas-Montanes, J., Reddy, V., von Andrian, U., Kang, D., & Lerner, E. (2018). Direct antigen-induced neural activation and recruitment are required for allergic eczema development. Nature.
Yoo, H., Kang, D., Katz, A. J., Lauwers, G. Y., Nishioka, N. S., Yagi, Y., Tanpowpong, P., Namati, J., Bouma, B. E., & Tearney, G. J. (2011). Reflectance confocal microscopy for the diagnosis of eosinophilic esophagitis: a pilot study conducted on biopsy specimens. Gastrointestinal endoscopy, 74(5), 992-1000.
Diagnosis of eosinophilic esophagitis (EoE) currently requires endoscopic biopsy and histopathologic analysis of the biopsy specimens to count intraepithelial eosinophils. Reflectance confocal microscopy (RCM) is an endomicroscopy technology that is capable of obtaining high-resolution, optically sectioned images of esophageal mucosa without the administration of exogenous contrast.
