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.
Kang, D., & Gweon, D. (2005). Two-dimensional imaging theory of confocal self-interference microscopy. Journal of the Optical Society of America. A, Optics, image science, and vision, 22(12), 2737-45.
A two-dimensional coherent imaging equation is derived for confocal self-interference microscopy (CSIM), which uses a birefringent material to generate an interference pattern in the detection optics. This interference pattern, called a self-interference pattern, sharpens the point-spread function (PSF) along the lateral direction. To derive the imaging equation, an equation for the self-interference pattern is derived. Numerical simulation results based on the imaging equation are presented. One-point response results show a 42.8% reduction in the FWHM of the lateral PSF. Two-point response results show a nearly twofold improvement in two-point resolution.
Kang, D., Yoo, H., Jillella, P., Bouma, B. E., & Tearney, G. J. (2011). Comprehensive volumetric confocal microscopy with adaptive focusing. Biomedical optics express, 2(6), 1412-22.
Comprehensive microscopy of distal esophagus could greatly improve the screening and surveillance of esophageal diseases such as Barrett's esophagus by providing histomorphologic information over the entire region at risk. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that can be configured to image the entire distal esophagus by helically scanning the beam using optics within a balloon-centering probe. It is challenging to image the human esophagus in vivo with balloon-based SECM, however, because patient motion and anatomic tissue surface irregularities decenter the optics, making it difficult to keep the focus at a predetermined location within the tissue as the beam is scanned. In this paper, we present a SECM probe equipped with an adaptive focusing mechanism that can compensate for tissue surface irregularity and dynamic focal variation. A tilted arrangement of the objective lens is employed in the SECM probe to provide feedback signals to an adaptive focusing mechanism. The tilted configuration also allows the probe to obtain reflectance confocal data from multiple depth levels, enabling the acquisition of three-dimensional volumetric data during a single scan of the probe. A tissue phantom with a surface area of 12.6 cm(2) was imaged using the new SECM probe, and 8 large-area reflectance confocal microscopy images were acquired over the depth range of 56 μm in 20 minutes. Large-area SECM images of excised swine small intestine tissue were also acquired, enabling the visualization of villous architecture, epithelium, and lamina propria. The adaptive focusing mechanism was demonstrated to enable acquisition of in-focus images even when the probe was not centered and the tissue surface was irregular.
