Dongkyun Kang

Interests

Teaching

Biomedical Optics; Biomedical instrumentation; Medical device development

Research

My research is focused on developing novel optical microscopy technologies and improving patient care using these technologies. My research area includes (1) lowcost smartphone in vivo microscopy, (2) high-speed comprehensive in vivo endomicroscopy, and (3) ultraminiature endomicroscopy.Low-cost smartphone in vivo microscopy: I am currently leading a NIH-sponsored research project for developing smartphone confocal microscope and diagnosing Kaposi's sarcoma in Uganda with the smartphone confocal microscope. I will further advance the smartphone microscopy technology and address other applications, including diagnosis of cervical and oral cancers in low-resource settings, large-population screening of skin cancers in the US, and aiding science and medical educations.High-speed comprehensive in vivo endomicroscopy: I have previously developed a high-speed confocal microscopy system and endoscopic imaging catheters and acquired largest in vivo confocal images of human organ reported. At the UA, I plan to further advance the technology by i) increasing the imaging speed by orders of magnitude and ii) incorporating fluorescence imaging modality.Ultraminiature endomicroscopy: In my previous research, I have developed miniature endoscopic catheters that can visualize internal organs in vivo through a needle-sized device. At the UA, I will develop microscopic imaging catheter with a extremely small diameter and utilize it for guiding cancer diagnosis and treatment.

Courses

Scholarly Contributions

Chapters

• Zhu, W., Gong, C., Kulkarni, N., Nguyen, C., & Kang, D. (2019). Smartphone based microscopes. In Smartphone based medical diagnostics.
• Do, D., Tearney, G. J., & Kang, D. (2017). Miniature confocal microscopy devices for imaging skin. In Reflectance confocal microscopy of cutaneous tumors.
• Woods, K., Kang, D., Neumann, H., Vieth, M., & Coron, E. (2014). Confocal Endomicroscopy. In Pathobiology of Human Disease.

Journals/Publications

• Barrios, A., Chung, A., Grant, C. N., Kang, D., Kim, J., Osman, H., Ryan, E., Ryu, J., & Tearney, G. J. (2023).

  High‐speed reflectance confocal microscopy of human skin at 1251–1342 nm

  . Lasers in Surgery and Medicine, 55(4), 405-413. doi:10.1002/lsm.23652
• Romero, R., Zhao, J., Stratton, D., Marcelino, K., Sugimura, M., Nichols, A., Gonzalez, S., Jain, M., Curiel‐Lewandrowski, C., & Kang, D. (2023).

  Handheld cross‐polarised microscope for imaging individual pigmented cells in human skin in vivo

  . Journal of Microscopy, 292(1), 47-55. doi:10.1111/jmi.13225
• Zhao, J., Kulkarni, N., Dobo, E., Khan, M. J., Yang, E., & Kang, D. (2022). Investigation of different wavelengths for scattering-based light sheet microscopy. Biomedical optics express, 13(7), 3882-3892.
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  Scattering-based light sheet microscopy (sLSM) is a microscopy technique that can visualize cellular morphologic details based on the scattering signal. While sLSM was previously shown to image animal tissues at a cellular resolution, the wavelength used was chosen based on other microscopy technologies rather than through a comparison of the sLSM imaging performance between different wavelengths. In this paper, we report the development of a multi-wavelength sLSM setup that facilitates the investigation of different wavelengths for sLSM imaging. Preliminary results of imaging human anal tissues showed that the sLSM setup allowed for comparisons of the cellular imaging performance at the same tissue location between different wavelengths. Both the quantitative analysis of the image contrast and the visual assessment by a pathologist showed that the imaging depth increased with wavelength, and the imaging depth increase was most notable around 600 nm. The preliminary results showed that the multi-wavelength sLSM setup could be useful in identifying the optimal wavelength for the specific tissue type.
• Curiel-Lewandrowski, C., Stratton, D. B., Gong, C., & Kang, D. (2021). Preliminary imaging of skin lesions with near-infrared, portable, confocal microscopy. Journal of the American Academy of Dermatology, 85(6), 1624-1625.
• Kang, D., Gmitro, A., Choi, H., Nishant, A., Kulkarni, N., Masciola, A., Kim, K., Freeman, E. E., Semeere, A., & Nakalembe, M. (2021). Low-cost, chromatic confocal endomicroscope for cellular imaging in vivo. Biomedical Optics Express, 12(9), 5629. doi:10.1364/boe.434892
• Kulkarni, N., Masciola, A., Nishant, A., Kim, K. J., Choi, H., Gmitro, A., Freeman, E. E., Semeere, A., Nakalembe, M., & Kang, D. (2021). Low-cost, chromatic confocal endomicroscope for cellular imaging. Biomedical optics express, 12(9), 5629-5643.
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  We have developed a low-cost, chromatic confocal endomicroscope (CCE) that can image a cross-section of the tissue at cellular resolution. In CCE, a custom miniature objective lens was used to focus different wavelengths into different tissue depths. Therefore, each tissue depth was encoded with the wavelength. A custom miniature spectrometer was used to spectrally-disperse light reflected from the tissue and generate cross-sectional confocal images. The CCE prototype had a diameter of 9.5 mm and a length of 68 mm. Measured resolution was high, 2 µm and 4 µm for lateral and axial directions, respectively. Effective field size was 468 µm. Preliminary results showed that CCE can visualize cellular details from cross-sections of the tissue down to the tissue depth of 100 µm.
• McMahon, D. E., Oyesiku, L., Semeere, A., Kang, D., & Freeman, E. E. (2021). Novel Diagnostics for Kaposi Sarcoma and Other Skin Diseases in Resource-Limited Settings. Dermatologic clinics, 39(1), 83-90.
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  In resource-limited settings, point-of-care diagnostic devices have the potential to reduce diagnostic delays and improve epidemiologic surveillance of dermatologic conditions. We outline novel-point-of care diagnostics that have recently been developed for dermatologic conditions that primarily affect patients living in resource-limited settings, namely, Kaposi sarcoma, cutaneous leishmaniasis, leprosy, Buruli ulcer, yaws, onchocerciasis, and lymphatic filariasis. All of the technologies described in this article are prototypes, and some have undergone field testing. These devices still require validation in real-world settings and effective pricing to have a major impact on dermatologic care in resource-limited settings.
• Ozcan, A., Kang, D., & Tearney, G. J. (2021). Introduction to Special Biomedical Optical Imaging Issue. Lasers in Surgery and Medicine, 53(6), 747-747. doi:10.1002/lsm.23413
• Seth, D., Kang, D., Tearney, G. J., Seth, D., Semeere, A., Rajadhyaksha, M., Oyesiku, L., Osman, H., Namaganda, P., Mcmahon, D. E., Martin, J. N., Lukande, R., Laker-oketta, M., Kang, D., Gonzalez, S., Freeman, E. E., & Anderson, R. R. (2021). Feasibility and implementation of portable confocal microscopy for point-of-care diagnosis of cutaneous lesions in a low-resource setting.. Journal of the American Academy of Dermatology, 84(2), 499-502. doi:10.1016/j.jaad.2020.04.147
• Yang, E., O'neal, P. K., Nguyen, C. D., Kulkarni, N., & Kang, D. (2021). Scattering-Based Light-Sheet Microscopy for Rapid Cellular Imaging of Fresh Tissue.. Lasers in surgery and medicine, 53(6), 872-879. doi:10.1002/lsm.23361
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  Light-sheet microscopy (LSM) is a novel imaging technology that has been used for imaging fluorescence contrast in basic life science research. In this paper, we have developed a scattering-based LSM (sLSM) for rapidly imaging the cellular morphology of fresh tissues without any exogenous fluorescent dyes..In the sLSM device, a thin light sheet with the central wavelength of 834 nm was incident on the tissue obliquely, 45° relative to the tissue surface. The detection optics was configured to map the light sheet-illuminated area onto a two-dimensional imaging sensor. The illumination numerical aperture (NA) was set as 0.0625, and the detection NA 0.3..The sLSM device achieved a light sheet thickness of less than 6.7 µm over 284 µm along the illumination optical axis. The detection optics of the sLSM device had a resolution of 1.8 µm. The sLSM images of the swine kidney ex vivo visualized tubules with similar sizes and shapes to those observed in histopathologic images. The swine duodenum sLSM images revealed cell nuclei and villi architecture in superficial lesions and glands in deeper regions..The preliminary results suggest that sLSM may have the potential for rapidly examining the freshly-excised tissue ex vivo or intact tissue in vivo at microscopic resolution. Further optimization and performance evaluation of the sLSM technology will be needed in the future. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
• Yelin, D., Tshikudi, D. M., Simandoux, O., Nadkarni, S. K., Kang, D., Cott, E. M., & Andrawes, M. N. (2021). Imaging the dynamics and microstructure of fibrin clot polymerization in cardiac surgical patients using spectrally encoded confocal microscopy.. American journal of hematology, 96(8), 968-978. doi:10.1002/ajh.26217
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  During cardiac surgery with cardiopulmonary bypass (CPB), altered hemostatic balance may disrupt fibrin assembly, predisposing patients to perioperative hemorrhage. We investigated the utility of a novel device termed spectrally-encoded confocal microscopy (SECM) for assessing fibrin clot polymerization following heparin and protamine administration in CPB patients. SECM is a novel, high-speed optical approach to visualize and quantify fibrin clot formation in three dimensions with high spatial resolution (1.0 μm) over a volumetric field-of-view (165 × 4000 × 36 μm). The measurement sensitivity of SECM was first determined using plasma samples from normal subjects spiked with heparin and protamine. Next, SECM was performed in plasma samples from patients on CPB to quantify the extent to which fibrin clot dynamics and microstructure were altered by CPB exposure. In spiked samples, prolonged fibrin time (4.4 ± 1.8 to 49.3 ± 16.8 min, p < 0.001) and diminished fibrin network density (0.079 ± 0.010 to 0.001 ± 0.002 A.U, p < 0.001) with increasing heparin concentration were reported by SECM. Furthermore, fibrin network density was not restored to baseline levels in protamine-treated samples. In CPB patients, SECM reported lower fibrin network density in protaminized samples (0.055 ± 0.01 A.U. [Arbitrary units]) vs baseline values (0.066 ± 0.009 A.U.) (p = 0.03) despite comparable fibrin time (baseline = 6.0 ± 1.3, protamine = 6.4 ± 1.6 min, p = 0.5). In these patients, additional metrics including fibrin heterogeneity, length and straightness were quantified. Note, SECM revealed that following protamine administration with CPB exposure, fibrin clots were more heterogeneous (baseline = 0.11 ± 0.02 A.U, protamine = 0.08 ± 0.01 A.U, p = 0.008) with straighter fibers (baseline = 0.918 ± 0.003A.U, protamine = 0.928 ± 0.0006A.U. p < 0.001). By providing the capability to rapidly visualize and quantify fibrin clot microstructure, SECM could furnish a new approach for assessing clot stability and hemostasis in cardiac surgical patients.
• Zhao, J., Kose, K., Kang, D., Jain, M., Harris, U. G., & Curiel-lewandrowski, C. (2021). Deep Learning-Based Denoising in High-Speed Portable Reflectance Confocal Microscopy.. Lasers in surgery and medicine, 53(6), 880-891. doi:10.1002/lsm.23410
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  Portable confocal microscopy (PCM) is a low-cost reflectance confocal microscopy technique that can visualize cellular details of human skin in vivo. When PCM images are acquired with a short exposure time to reduce motion blur and enable real-time 3D imaging, the signal-to-noise ratio (SNR) is decreased significantly, which poses challenges in reliably analyzing cellular features. In this paper, we evaluated deep learning (DL)-based approach for reducing noise in PCM images acquired with a short exposure time..Content-aware image restoration (CARE) network was trained with pairs of low-SNR input and high-SNR ground truth PCM images obtained from 309 distinctive regions of interest (ROIs). Low-SNR input images were acquired from human skin in vivo at the imaging speed of 180 frames/second. The high-SNR ground truth images were generated by registering 30 low-SNR input images obtained from the same ROI and summing them. The CARE network was trained using the Google Colaboratory Pro platform. The denoising performance of the trained CARE network was quantitatively and qualitatively evaluated by using image pairs from 45 unseen ROIs..CARE denoising improved the image quality significantly, increasing similarity with the ground truth image by 1.9 times, reducing noise by 2.35 times, and increasing SNR by 7.4 dB. Banding noise, prominent in input images, was significantly reduced in CARE denoised images. CARE denoising provided quantitatively and qualitatively better noise reduction than non-DL filtering methods. Qualitative image assessment by three confocal readers showed that CARE denoised images exhibited negligible noise more often than input images and non-DL filtered images..Results showed the potential of using a DL-based method for denoising PCM images obtained at a high imaging speed. The DL-based denoising method needs to be further trained and tested for PCM images obtained from disease-suspicious skin lesions.
• Gong, C., Stratton, D. B., Curiel-Lewandrowski, C. N., & Kang, D. (2020). Speckle-free, near-infrared portable confocal microscope. Applied optics, 59(22), G41-G46.
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  We have developed a portable confocal microscope (PCM) that uses an inexpensive near-infrared LED as the light source. Use of the spatially incoherent light source significantly reduced the speckle contrast. The PCM device was manufactured at the material cost of approximately 5000 and weighed only 1 kg. Lateral and axial resolutions were measured as 1.6 and 6.0 µm, respectively. Preliminary in vivo skin imaging experiment results showed that the PCM device could visualize characteristic cellular features of human skin extending from the stratum corneum to the superficial dermis. Dynamic imaging of blood flow in vivo was also demonstrated. The capability to visualize cellular features up to the superficial dermis is expected to facilitate evaluation and clinical adoption of this low-cost diagnostic imaging tool.
• Nguyen, C. D., O'Neal, P. K., Kulkarni, N., Yang, E., & Kang, D. (2020). Scattering-Based Light-Sheet Microscopy for Rapid Cellular Imaging of Fresh Tissue. Lasers in surgery and medicine.
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  Light-sheet microscopy (LSM) is a novel imaging technology that has been used for imaging fluorescence contrast in basic life science research. In this paper, we have developed a scattering-based LSM (sLSM) for rapidly imaging the cellular morphology of fresh tissues without any exogenous fluorescent dyes.
• Zhu, W., Pirovano, G., O'Neal, P. K., Gong, C., Kulkarni, N., Nguyen, C. D., Brand, C., Reiner, T., & Kang, D. (2020). Smartphone epifluorescence microscopy for cellular imaging of fresh tissue in low-resource settings. Biomedical optics express, 11(1), 89-98.
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  Disease diagnosis in low-resource settings can be challenging due to the lack of equipment and trained personnel required for histologic analysis. In this paper, we have developed a smartphone-based epifluorescence microscope (SeFM) for imaging fresh tissues at sub-cellular resolution. SeFM provides similar resolution and field of view (FOV) as those used during histologic analysis. The SeFM device achieved the lateral resolution of 0.57 µm and provided microscopy images over a sample area larger than 500 µm. The material cost was low, approximately $3,000. Preliminary images of human pancreatic tumor specimens clearly visualized cellular details. Quantitative analysis showed that using an excess dose of a chemotherapy drug significantly reduced the tumor-specific fluorescence signal, confirming the specificity of the drug and the detection potential of SeFM.
• Gong, C., Kulkarni, N., Zhu, W., Nguyen, C. D., Curiel-Lewandrowski, C., & Kang, D. (2019). Low-cost, high-speed near infrared reflectance confocal microscope. Biomedical optics express, 10(7), 3497-3505.
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  We have developed a low-cost, near-infrared (NIR) reflectance confocal microscope (RCM) to overcome challenges in the imaging depth and speed found in our previously-reported smartphone confocal microscope. In the new NIR RCM device, we have used 840 nm superluminescent LED (sLED) to increase the tissue imaging depth and speed. A new confocal detection optics has been developed to maintain high lateral resolution even when a relatively large slit width was used. The material cost of the NIR RCM device was still low, ~$5,200. The lateral resolution was 1.1 µm and 1.3 µm along the vertical and horizontal directions, respectively. Axial resolution was measured as 11.2 µm. confocal images of human forearm skin obtained at the imaging speed of 203 frames/sec clearly visualized characteristic epidermal and dermal cellular features of the human skin.
• Kang, D., Do, D., Ryu, J., Grant, C. N., Giddings, S. L., Rosenberg, M., Hesterberg, P. E., Yuan, Q., Garber, J. J., Katz, A. J., & Tearney, G. J. (2019). A miniaturized, tethered, spectrally-encoded confocal endomicroscopy capsule. Lasers in surgery and medicine.
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  The tethered spectrally-encoded confocal endomicroscopy (SECM) capsule is an imaging device that once swallowed by an unsedated patient can visualize cellular morphologic changes associated with gastrointestinal (GI) tract diseases in vivo. Recently, we demonstrated a tethered SECM capsule for counting esophageal eosinophils in patients with eosinophilic esophagitis (EoE) in vivo. Yet, the current tethered SECM capsule is far too long to be widely utilized for imaging pediatric patients, who constitute a major portion of the EoE patient population. In this paper, we present a new tethered SECM capsule that is 33% shorter, has an easier and repeatable fabrication process, and produces images with reduced speckle noise.
• Ryu, J., Kang, D., Do, D., Osman, H., Grant, C. N., Giddings, S., Baillargeon, A., Gao, A. H., Rosenberg, M., Yuan, Q., Garber, J. J., Katz, A. J., Tearney, G. J., & Hesterberg, P. E. (2019). Tu1963 AUTOMATED DIAGNOSIS OF EOSINOPHILIC ESOPHAGITIS FROM LARGE IMAGES OBTAINED BY SPECTRALLY-ENCODED TETHERED CAPSULE REFLECTANCE ENDOMICROSCOPY. Gastrointestinal Endoscopy, 89(6), AB633-AB634. doi:10.1016/j.gie.2019.03.1107
• Zeidan, A., Do, D., Kang, D., Ikuta, M., Ryu, J., & Tearney, G. J. (2019). High-Resolution, Wide-Field, Forward-Viewing Spectrally Encoded Endoscope. Lasers in surgery and medicine, 51(9), 808-814.
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  Spectrally encoded endoscopy (SEE) is an optical imaging technology that uses spatial wavelength multiplexing to conduct endoscopy in miniature, small diameter probes. Contrary to the previous side-viewing SEE devices, forward-viewing SEE probes are advantageous as they provide a look ahead that facilitates navigation and surveillance. The objective of this work was to develop a miniature forward-viewing SEE probe with a wide field of view and a high spatial resolution.
• Freeman, E. E., Semeere, A., Osman, H., Peterson, G., Rajadhyaksha, M., González, S., Martin, J. N., Anderson, R. R., Tearney, G. J., & Kang, D. (2018). Smartphone confocal microscopy for imaging cellular structures in human skin. Biomedical optics express, 9(4), 1906-1915.
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  We report development of a low-cost smartphone confocal microscope and its first demonstration of human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging.
• Ikuta, M., Kang, D., Do, D., Zeidan, A., & Tearney, G. J. (2018). Single-beam spectrally encoded color imaging. Optics letters, 43(10), 2229-2232.
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  We have developed, to the best of our knowledge, a new method of conducting spectrally encoded color imaging using a single light beam. In our method, a single broadband light beam was incident on a diffraction grating, where the overlapped third order of the red, fourth order of the green, and fifth order of the blue spectral bands were focused on a line illuminating tissue. This configuration enabled each point on the line to be illuminated by three distinctive wavelengths, corresponding to red, green, and blue. A custom grating was designed and fabricated to achieve high diffraction efficiencies for the wavelengths and diffraction orders used for color spectrally encoded imaging. A bench system was built to test the new spectrally encoded color imaging method. For a beam diameter of 174 μm, the bench system achieved 89,000 effective pixels over a 70° circular field. Spectrally encoded color images of excised swine tissue revealed blood vessels with a similar color appearance to those obtained via a conventional color camera. The results suggest that this single-beam spectrally encoded color method is feasible and can potentially simplify color spectrally encoded endoscopy probe designs.
• Tabatabaei, N., Kang, D., Kim, M., Wu, T., Grant, C. N., Rosenberg, M., Nishioka, N. S., Hesterberg, P. E., Garber, J., Yuan, Q., Katz, A. J., & Tearney, G. J. (2018). Clinical Translation of Tethered Confocal Microscopy Capsule for Unsedated Diagnosis of Eosinophilic Esophagitis. Scientific reports, 8(1), 2631.
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  Esophagogastroduodenoscopy (EGD) is a widely used procedure, posing significant financial burden on both healthcare systems and patients. Moreover, EGD is time consuming, sometimes difficult to tolerate, and suffers from an imperfect diagnostic yield as the limited number of collected biopsies does not represent the whole organ. In this paper, we report on technological and clinical feasibility of a swallowable tethered endomicroscopy capsule, which is administered without sedation, to image large regions of esophageal and gastric mucosa at the cellular level. To demonstrate imaging capabilities, we conducted a human pilot study (n = 17) on Eosinophilic Esophagitis (EoE) patients and healthy volunteers from which representative cases are presented and discussed. Results indicate that, compared to endoscopic biopsy, unsedated tethered capsule endomicroscopy obtains orders of magnitude more cellular information while successfully resolving characteristic tissue microscopic features such as stratified squamous epithelium, lamina propria papillae, intraepithelial eosinophils, and gastric cardia and body/fundic mucosa epithelia. Based on the major import of whole organ, cellular-level microscopy to obviate sampling error and the clear cost and convenience advantages of unsedated procedure, we believe that this tool has the potential to become a simpler and more effective device for diagnosing and monitoring the therapeutic response of EoE and other esophageal diseases.
• Tearney, G. J., & Kang, D. (2018). Introduction to biomedical optical imaging issue. Lasers in surgery and medicine, 50(3), 182.
• Do, D., Kang, D., Tabatabaei, N., Grant, C. N., Nishioka, N. S., Rosenberg, M., Hesterberg, P. E., Yuan, Q., Garber, J. J., Katz, A. J., Shreffler, W. G., & Tearney, G. J. (2017). Tethered SECM endoscopic capsule for the diagnosis of eosinophilic esophagitis (Conference Presentation). Proceedings of SPIE, 10040. doi:10.1117/12.2253401
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  Eosinophilic Esophagitis (EoE) is an inflammatory disease caused by inhaled or ingested food allergies, and characterized by the infiltration of eosinophils in the esophagus. The gold standard for diagnosing EoE is to conduct endoscopy and obtain multiple biopsy specimens from different portions of the esophagus; an exam is considered positive if more than 15 eosinophils per high power field (HPF) in any of the biopsies. This method of diagnosis is problematic because endoscopic biopsy is expensive and poorly tolerated and the esophageal eosinophil burden needs to be monitored frequently during the course of the disease. Spectrally encoded confocal microscopy (SECM) is a high-speed confocal microscopy technology that can visualize individual eosinophils in large microscopic images of the human esophagus, equivalent to more than 30,000 HPF. Previously, we have demonstrated that tethered capsule SECM can be conducted in unsedated subjects with diagnosed EoE. However, speckle noise and the relatively low resolution in images obtained with the first capsule prototypes made it challenging to distinguish eosinophils from other cells. In this work, we present a next-generation tethered SECM capsule, which has been modified to significantly improve image quality. First, we substituted the single mode fiber with a dual-clad fiber to reduce speckle noise. A gradient-index multimode fiber was fusion spliced at the tip of the dual-clad fiber to increase the effective numerical aperture of the fiber from 0.09 to 0.15, expanding the beam more rapidly to increase the illumination aperture at the objective. These modifications enabled the new SECM capsule to achieve a lateral resolution of 1.8 µm and an axial resolution of 16.1 µm, which substantially improves the capacity of this probe to visualize cellular features in human tissue. The total size of the SECM capsule remained 6.75 mm in diameter and 31 mm in length. We are now in the process of testing this new SECM capsule in humans. Early results using this new SECM capsule suggest that this technology has the potential to be an effective tool for the diagnosis of EoE.
• Kang, D., Schlachter, S. C., Carruth, R. W., Kim, M., Wu, T., Tabatabaei, N., Soomro, A. R., Grant, C. N., Rosenberg, M., Nishioka, N. S., & Tearney, G. J. (2017). Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo. Lasers in surgery and medicine, 49(3), 233-239.
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  Diagnosis of esophageal diseases is often hampered by sampling errors that are inherent in endoscopic biopsy, the standard of care. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal endomicroscopy technology that has the potential to visualize cellular features from large regions of the esophagus, greatly decreasing the likelihood of sampling error. In this paper, we report results from a pilot clinical study imaging the human esophagus in vivo with a prototype SECM endoscopic probe.
• Tearney, G. J., & Kang, D. (2017). Introduction to biomedical optical imaging. Lasers in surgery and medicine, 49(3), 214.
• 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.
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  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.
• 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 (SECM) for rapid assessment of breast excision specimens(Conference Presentation). Proceedings of SPIE, 9703. doi:10.1117/12.2209699
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  Unacceptably large percentage (20-40%) of breast cancer lumpectomy patients are required to undergo multiple surgeries when positive margins are found upon post-operative histologic assessment. If the margin status can be determined during surgery, surgeon can resect additional tissues to achieve tumor-free margin, which will reduce the need for additional surgeries. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has a potential to image the entire surgical margin within a short procedural time. Previously, SECM was shown to rapidly image a large area (10 mm by 10 mm) of human esophageal tissue within a short procedural time (15 seconds). When used in lumpectomy, SECM will be able to image the entire margin surface of ~30 cm2 in around 7.5 minutes. SECM images will then be used to determine margin status intra-operatively. In this paper, we present results from a study of testing accuracy of SECM for diagnosing malignant breast tissues. We have imaged freshly-excised breast specimens (N=46) with SECM. SECM images clearly visualized histomorphologic features associated with normal/benign and malignant breast tissues in a similar manner to histologic images. Diagnostic accuracy was tested by comparing SECM diagnoses made by three junior pathologists with corresponding histologic diagnoses made by a senior pathologist. SECM sensitivity and specificity were high, 0.91 and 0.93, respectively. Intra-observer agreement and inter-observer agreement were also high, 0.87 and 0.84, respectively. Results from this study showed that SECM has a potential to accurately determine margin status during breast cancer lumpectomy.
• Do, D., Alali, S., Kang, D., Tabatabaie, N., Lu, W., Grant, C. N., Soomro, A. R., Nishioka, N. S., Rosenberg, M., Hesterberg, P. E., Yuan, Q., Garber, J. J., Katz, A. J., Shreffler, W. G., & Tearney, G. J. (2016). Clinical experience using the tethered capsule-based spectrally encoded confocal microendoscopy for diagnosis of eosinophilic esophagitis(Conference Presentation). Proceedings of SPIE, 9691. doi:10.1117/12.2218559
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  Eosinophilic Esophagitis (EoE) is caused by food allergies, and defined by histological presence of eosinophil cells in the esophagus. The current gold standard for EoE diagnosis is endoscopy with pinch biopsy to detect more than 15 eosinophils/ High power field (HPF). Biopsy examinations are expensive, time consuming and are difficult to tolerate for patients. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology capable of imaging individual eosinophils as highly scattering cells (diameter between 8 µm to 15 µm) in the epithelium. Our lab has developed a tethered SECM capsule that can be swallowed by unsedated patients. The capsule acquires large area confocal images, equivalent to more than 30,000 HPFs, as it traverses through the esophagus. In this paper, we present the outcome of a clinical study using the tethered SECM capsule for diagnosing EoE. To date, 32 subjects have been enrolled in this study. 88% of the subjects swallowed the capsules without difficulty and of those who swallowed the capsule, 95% preferred the tethered capsule imaging procedure to sedated endoscopic biopsy. Each imaging session took about 12 ± 2.4 minutes during which 8 images each spanning of 24 ± 5 cm2 of the esophagus were acquired. SECM images acquired from EoE patients showed abundant eosinophils as highly scattering cells in squamous epithelium. Results from this study suggest that the SECM capsule has the potential to become a less-invasive, cost-effective tool for diagnosing EoE and monitoring the response of this disease to therapy.
• Do, D., Kang, D., Ikuta, M., & Tearney, G. J. (2016). Simple, monolithic optical element for forward-viewing spectrally encoded endoscopy (Conference Presentation). Proceedings of SPIE, 9691. doi:10.1117/12.2213394
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  Spectrally encoded endoscopy (SEE) is a miniature endoscopic technology that can acquire images of internal organs through a hair-thin probe. While most previously described SEE probes have been side viewing, forward-view (FV)-SEE is advantageous in certain clinical applications as it provides more natural navigation of the probe and has the potential to provide a wider field of view. Prior implementations of FV-SEE used multiple optical elements that increase fabrication complexity and may diminish the robustness of the device. In this paper, we present a new design that uses a monolithic optical element to realize FV-SEE imaging. The optical element is specially designed spacer, fabricated from a 500-μm-glass rod that has a mirror surface on one side and a grating stamped on its distal end. The mirror surface is used to change the incident angle on the grating to diffract the shortest wavelength of the spectrum so that it is parallel to the optical axis. Rotating the SEE optics creates a circular FV-SEE image. Custom-designed software processes FV-SEE images into circular images, which are displayed in real-time. In order to demonstrate this new design, we have constructed the FV-SEE optical element using a 1379 lines/mm diffraction grating. When illuminated with a source with a spectral bandwidth of 420-820 nm, the FV-SEE optical element provides 678 resolvable points per line. The imaging performance of the FV-SEE device was tested by imaging a USAF resolution target. SEE images showed that this new approach generates high quality images in the forward field with a field of view of 58°. Results from this preliminary study demonstrate that we can realize FV-SEE imaging with simple, monolithic, miniature optical element. The characteristics of this FV-SEE configuration will facilitate the development of robust miniature endoscopes for a variety of medical imaging applications.
• Kang, D., Kim, M., Carruth, R. W., Lu, W., Wu, T., Alali, S., Do, D., Soomro, A. R., Grant, C. N., Tiernan, A. R., Rosenberg, M., Nishioka, N. S., & Tearney, G. J. (2016). SECM half-inch tethered endoscopic capsule (HITEC) for esophageal imaging (Conference Presentation). Proceedings of SPIE, 9691. doi:10.1117/12.2208942
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  Spectrally encoded confocal microscopy (SECM) is a high-speed confocal endomicroscopy technology that can image extremely large regions of human tissue at cellular resolution within a short imaging time. Previously, we have developed a 7-mm-diameter SECM endoscopic capsule and successfully demonstrated imaging of human esophagus in vivo. Even though we were able to successfully capture images with the previous capsule, it suffered from two limitations: (1) the capsule had a small diameter, which provided a limited contact between SECM capsule and esophagus; and (2) speckle noise in SECM images made it challenging to appreciate cellular features. In this paper, we present a new SECM capsule, termed SECM half-inch tethered endoscopic capsule (HITEC), which addresses the two aforementioned technical challenges. With the SECM HITEC, a dual-clad fiber was used to reduce the speckle noise. Miniature GRIN optics was used to increase the NA of the fiber from 0.09 to 0.25, which made it possible to build a SECM capsule with large diameter (12.7 mm) while maintaining a short rigid length (22 mm). A water-immersion objective lens was custom designed and manufactured to provide high NA of 0.7. We have manufactured the SECM HITEC catheter and tested its optical and mechanical performance. Lateral and axial resolution was measured as 1.2 µm and 13 µm, respectively. We have imaged swine esophageal tissues ex vivo, and SECM images clearly visualized cell nuclei. Non-uniform rotational distortion (NURD) was small, less than 5%. Preliminary results suggest that SECM HITEC provides sufficient optical and mechanical performance for tissue imaging. In a future clinical study, we will test the feasibility of utilizing SECM HITEC for improved cellular imaging human of the human esophagus in vivo.
• Kang, D., Schlachter, S. C., Carruth, R. W., Kim, M., Wu, T., Tabatabaei, N., Soomro, A. R., Grant, C. N., Tiernan, A. R., Rosenberg, M., Nishioka, N. S., & Tearney, G. J. (2015). Su1713 Comprehensive Confocal Endomicroscopy of Barrett's Esophagus. Gastrointestinal Endoscopy, 81(5), AB387. doi:10.1016/j.gie.2015.03.1562
• Tabatabaei, N., Kang, D., Lu, W., Wu, T., Kim, M., Carruth, R. W., Soomro, A. R., Grant, C. N., Tiernan, A. R., Rosenberg, M., Sauk, J., Hesterberg, P. E., Nishioka, N. S., Yuan, Q., Katz, A. J., Tearney, G. J., & Garber, J. J. (2015). 628 In Vivo Imaging of Eosinophils With a Tethered Confocal Endomicroscopy Capsule. Gastrointestinal Endoscopy, 81(5), AB158-AB159. doi:10.1016/j.gie.2015.03.103
• Brachtel, E. F., Smith, B. L., Tearney, G. J., & Kang, D. (2014). Spectrally Encoded Confocal Microscopy for Guiding Lumpectomy. Analytical Cellular Pathology, 2014, 1-2. doi:10.1155/2014/573851
• Kang, D., Schlachter, S. C., Carruth, R. W., Kim, M., Wu, T., Tabatabaei, N., Vacas-Jacques, P., Shishkov, M., Woods, K., Sauk, J. S., Leung, J., Nishioka, N. S., & Tearney, G. J. (2014). Comprehensive confocal endomicroscopy of the esophagus in vivo. Endoscopy international open, 2(3), E135-40.
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  Biopsy sampling error can be a problem for the diagnosis of certain gastrointestinal tract diseases. Spectrally-encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has the potential to overcome sampling error by imaging large regions of gastrointestinal tract tissues. The aim of this study was to test a recently developed SECM endoscopic probe for comprehensively imaging large segments of the esophagus at the microscopic level in vivo.
• Kim, M., Kang, D., Wu, T., Tabatabaei, N., Carruth, R. W., Martinez, R. V., Whitesides, G. M., Nakajima, Y., & Tearney, G. J. (2014). Miniature objective lens with variable focus for confocal endomicroscopy. Biomedical optics express, 5(12), 4350-61.
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  Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that can rapidly image large areas of luminal organs at microscopic resolution. One of the main challenges for large-area SECM imaging in vivo is maintaining the same imaging depth within the tissue when patient motion and tissue surface irregularity are present. In this paper, we report the development of a miniature vari-focal objective lens that can be used in an SECM endoscopic probe to conduct adaptive focusing and to maintain the same imaging depth during in vivo imaging. The vari-focal objective lens is composed of an aspheric singlet with an NA of 0.5, a miniature water chamber, and a thin elastic membrane. The water volume within the chamber was changed to control curvature of the elastic membrane, which subsequently altered the position of the SECM focus. The vari-focal objective lens has a diameter of 5 mm and thickness of 4 mm. A vari-focal range of 240 μm was achieved while maintaining lateral resolution better than 2.6 μm and axial resolution better than 26 μm. Volumetric SECM images of swine esophageal tissues were obtained over the vari-focal range of 260 μm. SECM images clearly visualized cellular features of the swine esophagus at all focal depths, including basal cell nuclei, papillae, and lamina propria.
• Kang, D., Carruth, R. W., Kim, M., Schlachter, S. C., Shishkov, M., Woods, K., Tabatabaei, N., Wu, T., & Tearney, G. J. (2013). Endoscopic probe optics for spectrally encoded confocal microscopy. Biomedical optics express, 4(10), 1925-36.
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  Spectrally encoded confocal microscopy (SECM) is a form of reflectance confocal microscopy that can achieve high imaging speeds using relatively simple probe optics. Previously, the feasibility of conducting large-area SECM imaging of the esophagus in bench top setups has been demonstrated. Challenges remain, however, in translating SECM into a clinically-useable device; the tissue imaging performance should be improved, and the probe size needs to be significantly reduced so that it can fit into luminal organs of interest. In this paper, we report the development of new SECM endoscopic probe optics that addresses these challenges. A custom water-immersion aspheric singlet (NA = 0.5) was developed and used as the objective lens. The water-immersion condition was used to reduce the spherical aberrations and specular reflection from the tissue surface, which enables cellular imaging of the tissue deep below the surface. A custom collimation lens and a small-size grating were used along with the custom aspheric singlet to reduce the probe size. A dual-clad fiber was used to provide both the single- and multi- mode detection modes. The SECM probe optics was made to be 5.85 mm in diameter and 30 mm in length, which is small enough for safe and comfortable endoscopic imaging of the gastrointestinal tract. The lateral resolution was 1.8 and 2.3 µm for the single- and multi- mode detection modes, respectively, and the axial resolution 11 and 17 µm. SECM images of the swine esophageal tissue demonstrated the capability of this device to enable the visualization of characteristic cellular structural features, including basal cell nuclei and papillae, down to the imaging depth of 260 µm. These results suggest that the new SECM endoscopic probe optics will be useful for imaging large areas of the esophagus at the cellular scale in vivo.
• 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.
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  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.
• Kang, D., Schlachter, S. C., Carruth, R. W., Kim, M., Wu, T., Tabatabaei, N., Woods, K. E., Sauk, J., Nishioka, N. S., & Tearney, G. J. (2013). Mo1630 Comprehensive Esophageal Cellular Imaging With Spectrally-Encoded Confocal Endomicroscopy. Gastrointestinal Endoscopy, 77(5), AB451. doi:10.1016/j.gie.2013.03.378
• Schlachter, S. C., Kang, D., Gora, M. J., Vacas-Jacques, P., Wu, T., Carruth, R. W., Wilsterman, E. J., Bouma, B. E., Woods, K., & Tearney, G. J. (2013). Spectrally encoded confocal microscopy of esophageal tissues at 100 kHz line rate. Biomedical optics express, 4(9), 1636-45.
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  Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that uses a diffraction grating to illuminate different locations on the sample with distinct wavelengths. SECM can obtain line images without any beam scanning devices, which opens up the possibility of high-speed imaging with relatively simple probe optics. This feature makes SECM a promising technology for rapid endoscopic imaging of internal organs, such as the esophagus, at microscopic resolution. SECM imaging of the esophagus has been previously demonstrated at relatively low line rates (5 kHz). In this paper, we demonstrate SECM imaging of large regions of esophageal tissues at a high line imaging rate of 100 kHz. The SECM system comprises a wavelength-swept source with a fast sweep rate (100 kHz), high output power (80 mW), and a detector unit with a large bandwidth (100 MHz). The sensitivity of the 100-kHz SECM system was measured to be 60 dB and the transverse resolution was 1.6 µm. Excised swine and human esophageal tissues were imaged with the 100-kHz SECM system at a rate of 6.6 mm(2)/sec. Architectural and cellular features of esophageal tissues could be clearly visualized in the SECM images, including papillae, glands, and nuclei. These results demonstrate that large-area SECM imaging of esophageal tissues can be successfully conducted at a high line imaging rate of 100 kHz, which will enable whole-organ SECM imaging in vivo.
• Tabatabaei, N., Kang, D., Leung, J., Carruth, R. W., Wu, T., Kim, M., Brizard, S. A., Shreffler, W. G., Yuan, Q., Katz, A. J., & Tearney, G. J. (2013). Mo1632 Development of a Confocal Endomicroscopy Capsule for Diagnosis of Eosinophilic Esophagitis. Gastrointestinal Endoscopy, 77(5), AB452. doi:10.1016/j.gie.2013.03.380
• Tabatabaei, N., Kang, D., Wu, T., Kim, M., Carruth, R. W., Leung, J., Sauk, J. S., Shreffler, W., Yuan, Q., Katz, A., Nishioka, N. S., & Tearney, G. J. (2013). Tethered confocal endomicroscopy capsule for diagnosis and monitoring of eosinophilic esophagitis. Biomedical optics express, 5(1), 197-207.
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  Eosinophilic esophagitis (EoE) is an allergic condition that is characterized by eosinophils infiltrating the esophageal wall. The treatment of the disease may require multiple follow up sedated endoscopies and biopsies to confirm elimination of eosinophils. These procedures are expensive, time consuming, and may be difficult for patients to tolerate. Here we report on the development of a confocal microscopy capsule for diagnosis and monitoring of EoE. The swallowable capsule implements a high-speed fiber-based reflectance confocal microscopy technique termed Spectrally Encoded Confocal Microscopy (SECM). SECM scans the sample in one dimension without moving parts by using wavelength swept source illumination and a diffraction grating at the back plane of the objective lens. As the wavelength of the source is tuned, the SECM optics within the 7 x 30 mm capsule are rotated using a driveshaft enclosed in a 0.8 mm flexible tether. A single rotation of the optics covered a field of view of 22 mm x 223 µm. The lateral and axial resolutions of the device were measured to be 2.1 and 14 µm, respectively. Images of Acetic Acid stained swine esophagus obtained with the capsule ex vivo and in vivo clearly showed squamous epithelial nuclei, which are smaller and less reflective than eosinophils. Imaging of esophageal biopsies from EoE patients ex vivo demonstrated the capability of this technology to visualize individual eosinophils. Based on the results of this study, we believe that this capsule will be a simpler and more effective device for diagnosing EoE and monitoring the therapeutic response of this disease.
• Unglert, C. I., Namati, E., Warger, W. C., Liu, L., Yoo, H., Kang, D., Bouma, B. E., & Tearney, G. J. (2012). Evaluation of optical reflectance techniques for imaging of alveolar structure. Journal of biomedical optics, 17(7), 071303.
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  Three-dimensional (3-D) visualization of the fine structures within the lung parenchyma could advance our understanding of alveolar physiology and pathophysiology. Current knowledge has been primarily based on histology, but it is a destructive two-dimensional (2-D) technique that is limited by tissue processing artifacts. Micro-CT provides high-resolution three-dimensional (3-D) imaging within a limited sample size, but is not applicable to intact lungs from larger animals or humans. Optical reflectance techniques offer the promise to visualize alveolar regions of the large animal or human lung with sub-cellular resolution in three dimensions. Here, we present the capabilities of three optical reflectance techniques, namely optical frequency domain imaging, spectrally encoded confocal microscopy, and full field optical coherence microscopy, to visualize both gross architecture as well as cellular detail in fixed, phosphate buffered saline-immersed rat lung tissue. Images from all techniques were correlated to each other and then to corresponding histology. Spatial and temporal resolution, imaging depth, and suitability for in vivo probe development were compared to highlight the merits and limitations of each technology for studying respiratory physiology at the alveolar level.
• Kang, D., Bouma, B. E., & Tearney, G. J. (2011). Spectrally encoded imaging. Frontiers in Optics. doi:10.1364/fio.2011.fml6
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  Spectrally encoded imaging is a high-speed endoscopic imaging technology that encodes a transverse coordinate of the sample in the wavelength. We will discuss spectrally encoded confocal microscopy and spectrally encoded endoscopy.
• 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.
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  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.
• 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.
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  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. K., Suter, M. J., Boudoux, C., Yachimski, P. S., Puricelli, W. P., Nishioka, N. S., Mino-kenudson, M., Lauwers, G. Y., Bouma, B. E., & Tearney, G. J. (2010). Co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system.. Journal of microscopy, 239(2), 87-91. doi:10.1111/j.1365-2818.2010.03367.x
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  Spectrally encoded confocal microscopy and optical frequency domain imaging are two non-contact optical imaging technologies that provide images of tissue cellular and architectural morphology, which are both used for histopathological diagnosis. Although spectrally encoded confocal microscopy has better transverse resolution than optical frequency domain imaging, optical frequency domain imaging can penetrate deeper into tissues, which potentially enables the visualization of different morphologic features. We have developed a co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system and have obtained preliminary images from human oesophageal biopsy samples to compare the capabilities of these imaging techniques for diagnosing oesophageal pathology.
• Kang, D., Suter, M. J., Boudoux, C., Yoo, H., Yachimski, P. S., Puricelli, W. P., Nishioka, N. S., Mino-Kenudson, M., Lauwers, G. Y., Bouma, B. E., & Tearney, G. J. (2010). Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy. Gastrointestinal endoscopy, 71(1), 35-43.
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  Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution.
• Unglert, C., Namati, E., Liu, L., Yoo, H., Kang, D., Tearney, G. J., & Bouma, B. E. (2010). Reflectance microscopy techniques for 3D imaging of the alveolar structure. Head & Neck Oncology, 2(1), 1-1. doi:10.1186/1758-3284-2-s1-o12
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  Lung disease involving the alveoli and distal bronchioles are poorly understood and most commonly studied indirectly via lung function tests. Available imaging tools for the non-destructive assessment of the alveolar structure include X-ray computed tomography, intra-vital fluorescence microscopy and Optical Coherence Tomography, which are either limited by long acquisition time, inadequate resolution and contrast, or shallow imaging depth. In this study, we investigated the potential of two high-resolution reflectance microscopy imaging techniques, Spectrally Encoded Confocal Microscopy (SECM; 1µm (x) x 1µm (y) x 5µm (z) resolution) and Full Field Optical Coherence Microscopy (FFOCM; 1µm (x) x 1µm (y) x 1µm (z) resolution), for imaging alveolar microstructural detail. Two mouse lung samples were imaged with both SECM and FFOCM. The specimens were inflation-fixed using a modified Heitzman fixation technique at 20 cm H2O pressure. They were cut in 500mm thick slices and water immersed for imaging. Images were obtained and analyzed to determine whether or not the resolution and contrast of these techniques are sufficient to visualize the fine structures of the alveolar wall. Alveolar microstructure could be resolved in three dimensions in images obtained by both technologies. Alveolar septal walls from multiple layers could be clearly identified while sub-cellular structures such as nuclei were also visible in the SECM technique. In conclusion, we have demonstrated that two imaging technologies provide important sub-cellular detail that is required to study alveolar microstructure. Future research to develop these imaging modalities further so that they may be used in vivo is merited.
• Kang, D., Suter, M. J., Boudoux, C., Yachimski, P. S., Nishioka, N. S., Mino-kenudson, M., Lauwers, G. Y., Bouma, B. E., & Tearney, G. J. (2009). Combined Reflection Confocal Microscopy and Optical Coherence Tomography Imaging of Esophageal Biopsy. Gastrointestinal Endoscopy, 69(5), AB368. doi:10.1016/j.gie.2009.03.1101
• Kang, D., Yelin, D., Bouma, B. E., & Tearney, G. J. (2009). Spectrally-encoded color imaging. Optics express, 17(17), 15239-47.
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  Spectrally-encoded endoscopy (SEE) is a technique for ultraminiature endoscopy that encodes each spatial location on the sample with a different wavelength. One limitation of previous incarnations of SEE is that it inherently creates monochromatic images, since the spectral bandwidth is expended in the spatial encoding process. Here we present a spectrally-encoded imaging system that has color imaging capability. The new imaging system utilizes three distinct red, green, and blue spectral bands that are configured to illuminate the grating at different incident angles. By careful selection of the incident angles, the three spectral bands can be made to overlap on the sample. To demonstrate the method, a bench-top system was built, comprising a 2400-lpmm grating illuminated by three 525-microm-diameter beams with three different spectral bands. Each spectral band had a bandwidth of 75 nm, producing 189 resolvable points. A resolution target, color phantoms, and excised swine small intestine were imaged to validate the system's performance. The color SEE system showed qualitatively and quantitatively similar color imaging performance to that of a conventional digital camera.
• Gweon, D., Lee, S., Yoo, H., Lee, S., Kim, T., Kang, D., & Kim, K. (2006). Confocal Scanning Microscopy : a High-Resolution Nondestructive Surface Profiler. International Journal of Precision Engineering and Manufacturing, 7(4), 3-7.
• Kim, J., Kang, D., & Gweon, D. (2006). Spectrally encoded slit confocal microscopy. Optics letters, 31(11), 1687-9.
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  A simple and cost-effective method for real-time imaging in confocal microscopy is proposed. Spectrally encoded slit confocal microscopy (SESCoM) uses a spectral encoding technique together with a confocal slit aperture to achieve two-dimensional images. Simulation and experimental results of the SESCoM's axial and lateral performances are presented. The measured FWHM of the axial response is 1.15 mum when an objective with a NA of 0.95 is used. FWHMs of the lateral line spread functions are measured to be 236 and 244 nm along the x and y directions, respectively. Both the axial and the lateral experimental results agree well with the simulation results.
• Yoo, H., Lee, S., Kang, D., Kim, T., Gweon, D., Lee, S., & Kim, K. (2006). Confocal Scanning Microscopy. International Journal of Precision Engineering and Manufacturing, 7(4), 3-7.
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  Confocal scanning microscopy is a measurement technique used to observe micrometer and sub-micrometer features due to its high resolution, nondestructive properties, and 3D surface profiling capabilities. The design, implementation, and performance test of a confocal scanning microscopy system are presented in this paper. A short-wavelength laser (405 ㎚) and an objective lens with a high numerical aperture (0.95) were used to achieve the desired high resolution, while the x-and y-axis scans were implemented using an acousto-optic deflector and galvanomirror, respectively. An objective lens with a piezo-actuator was used to scan the z-axis. A spatial resolution of less than 138 ㎚ was achieved, along with successful 3D surface reconstructions.
• Kang, D., & Gweon, D. (2005). Image of a straight edge in confocal self-interference microscopy. Optics letters, 30(13), 1650-2.
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  An image of a straight edge in confocal self-interference microscopy (CSIM) is analyzed. Simulations of edge images based on a two-dimensional imaging equation are presented that show a 103% increase in edge gradient and a 43.1% decrease in the 10-90% width. The first experimental results, to our knowledge, for CSIM are presented and show good agreement with the simulation results and a 23% decrease in the 10-90% width.
• Kang, D., & Gweon, D. (2005). Lateral resolution enhancement in confocal self-interference microscopy. Biomedical optics, 5701, 152-163. doi:10.1117/12.589526
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  Lateral resolution enhancement in confocal self-interference microscopy (CSIM) is evaluated. CSIM, which uses the birefringence of the calcite plate to generate self-interference pattern, sharpens the central lobe of the effective spot. Numerical simulation results of two-dimensional imaging performances are presented. Two-point resolution of 149nm is achieved, which is enhanced by nearly 100% compared to that of confocal microscopy.
• 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.
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  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., Lee, S., & Gweon, D. (2005). Lateral Resolution Enhancement in Confocal Self-interference Microscopy with Commercial Calcite Plate. Journal of The Optical Society of Korea, 9(1), 32-35. doi:10.3807/josk.2005.9.1.032
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  In light microscopy, spatial resolution is limited by diffraction effect. Confocal microscopy has improved resolutions in both lateral and axial directions, but these are still limited by diffraction effect. Confocal self-interference microscopy (CSIM) uses interference between two perpendicularly polarized beams to enhance lateral resolution. In previous research, we proposed a calcite plate with its optic-axis perpendicular to the propagation angle and one of the boundary surfaces of the plate. This type of plate is not widely used to our knowledge. In this paper, we change the calcite plate to more common one, which is commercially available. This calcite plate has its optic axis in the plane of incidence. We analyze the characteristics of this calcite plate and numerically compare the performances of CSIM in previous research and CSIM with the commercial calcite plate. Numerical results show improved performance when using the commercial calcite plate
• Lee, S., Kang, D., Yoo, H., Kim, T., Gweon, D., Lee, S., Kim, K., & Lee, S. (2005). Measurement of Sub-micrometer Features Based on The Topographic Contrast Using Reflection Confocal Microscopy. Journal of The Optical Society of Korea, 9(1), 26-31. doi:10.3807/josk.2005.9.1.026
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  We describe the design and the implementation of video-rate reflection confocal scanning microscopy (CSM) using an acousto-optical deflector (AOD) for the fast horizontal scan and a galvanometer mirror (GM) for the slow vertical scan. Design parameters of the optical system are determined for optimal resolution and contrast. The OSLO simulations show that the performances of CSM are not changed with deflection angle and the wavefront errors of the system are less than 0.012λ. To evaluate the performances of designed CSM, we do a series of tests, measuring lateral and axial resolution, real time image acquisition. Due to a higher axial resolution compared with conventional microscopy, CSM can detect the surface of sub-micrometer features. We detect 138㎚ line shape pattern with a video-rate (30 frm/sec). And 10㎚ axial resolution is archived. The lateral resolution of the topographic images will be further enhanced by differential confocal microscopy (DCM) method and computational algorithms.
• Kang, D., Seo, J. W., & Gweon, D. (2004). Improvement of detected intensity in confocal microscopy by using reflecting optical system. Review of Scientific Instruments, 75(2), 550-552. doi:10.1063/1.1638895
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  In confocal microscopy, the level of the detected intensity is low, which reduces the contrast of the images. We propose a reflecting optical system to improve the detected intensity. The result of the optimal design is presented and the performance of the resulting reflecting optical system is evaluated. A numerical simulation of the effect of the reflecting optical system on the total system performance is also presented. A standard specimen is imaged to show the benefits of the proposed reflecting optical system. The results in this Note demonstrate a 37% increase of the detected intensity and better contrast of the image.
• Lee, S., Kang, D., Yoo, H., Gweon, D., Lee, S., Kim, K., Lee, S., & Lee, S. (2004). Design and performance evaluation of reflection confocal microscopy using acousto-optical deflector and slit detector. Biomedical optics, 5324(13), 235-241. doi:10.1117/12.529884
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  We describe the design and the implementation of reflection confocal scanning microscopy (CSM) using an acousto-optical deflector (AOD) for the fast horizontal scan and a galvanometer mirror (GM) for the slow vertical scan. In the beam scanning system it is important to maintain the lateral and the axial performance during scanning operation. We propose a simple method to design a scanning system using the finite ray tracing and the diffraction theory. We define a cost function which contains the effect of aberrations on the performance of microscopy. We construct the designed system and evaluate its performance. The OSLO simulation shows that the performances of CSM are not changed with deflection angle. So we conclude that the beam scanning system is properly designed. In addition, we propose an image formation method and show images obtained with the system.
• Yoo, H., Lee, S., Lee, J. H., Kang, D., & Gweon, D. (2004). Error analysis and tolerance allocation for confocal scanning microscopy using the Monte Carlo method. Biomedical optics, 5324(13), 242-249. doi:10.1117/12.529942
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  The errors can cause the serious loss of the performance of a precision machine system. In this paper, we propose the method of allocating the alignment tolerances of the components and apply this method to Confocal Scanning Microscopy (CSM) to get the optimal tolerances. CSM uses confocal aperture, which blocks the out-of-focus information. Thus, it provides images with superior resolution and has unique property of optical sectioning. Recently, due to these properties, it has been widely used for measurement in biological field, medical science, material science and semiconductor industry. In general, tight tolerances are required to maintain the performance of a system, but a high cost of manufacturing and assembling is required to preserve the tight tolerances. The purpose of allocating the optimal tolerances is minimizing the cost while keeping the performance of the system. In the optimal problem, we set the performance requirements as constraints and maximized the tolerances. The Monte Carlo Method, a statistical simulation method, is used in tolerance analysis. Alignment tolerances of optical components of the confocal scanning microscopy are optimized, to minimize the cost and to maintain the observation performance of the microscopy. We can also apply this method to the other precision machine system.
• Kang, D., & Gweon, D. (2003). Enhancement of lateral resolution in confocal self-interference microscopy. Optics letters, 28(24), 2470-2.
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  We describe confocal self-interference microscopy with enhanced lateral resolution. A uniaxial anisotropic crystal is used to cause interference between two linearly polarized beams that are reflected from the same pointlike object in the focal plane of the objective lens. Theory and the optimal design that maximizes the sensitivity of the interference signal are presented. A numerical experiment shows a 38% decrease in the lateral FWHM for simple confocal self-interference microscopy.

Proceedings Publications

• Zhao, J., Kose, K., Kang, D., Jain, M., Harris, U., & Curiel-lewandrowski, C. (2021). Deep learning-based denoising in spectrally-encoded confocal microscopy. In Endoscopic Microscopy XVI, 11620.
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  In this paper, we demonstrate deep learning-based denoising of high-speed (180 fps) confocal images obtained with our low-cost SECM device. The CARE network was trained with 3090 high- and low-SNR image pairs on the Google Colab platform and tested with 45 unseen image pairs. The CARE prediction showed significant increase of SSIM and PSNR, and reduction of the banding noise while maintaining the cellular details. The preliminary results show the potential of using a deep learning-based denoising approach to enable high-speed SECM imaging.
• Kang, D., Gong, C., & Chidambaram, J. D. (2020). Cellular imaging of the cornea with a low-cost, portable confocal microscope. In Biophotonics Congress: Biomedical Optics 2020 (Translational, Microscopy, OCT, OTS, BRAIN).
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  We tested the feasibility of imaging cellular features of the cornea using a low-cost portable confocal microscope (PCM). Preliminary PCM images clearly visualized characteristic cellular details throughout the entire thickness of the cornea.
• Gong, C., Gong, C., Kulkarni, N., Kulkarni, N., Zhu, W., Zhu, W., Nguyen, C. D., Nguyen, C. D., Curiel-lewandrowski, C., Curiel-lewandrowski, C., Kang, D., & Kang, D. (2019). High-Speed Blood Flow Imaging with Scanless Confocal Microscope. In 2019 IEEE Photonics Conference (IPC).
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  We have developed a scanless confocal microscope and demonstrated high-speed cellular imaging of the human skin in vivo. Using the high imaging speed of 203 frames/sec, rapid blood flow was well visualized.
• Gong, C., Kulkarni, N., Zhu, W., Nguyen, C. D., Curiel-lewandrowski, C., & Kang, D. (2019). Low-cost, high-speed near-infrared confocal microscope. In Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA,BRAIN,NTM,OMA,OMP).
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  We developed a low-cost, high-speed near infrared confocal microscope. Material cost was approximately $5,000. In vivo confocal images of human skin acquired at 203 frame/sec clearly visualized cellular features, including keratinocytes and melanocytes.
• Nguyen, C. D., Gong, C., Kulkarni, N., Zhu, W., Curiel-lewandrowski, C., & Kang, D. (2019). Light sheet microscopy of human skin in vivo. In Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA,BRAIN,NTM,OMA,OMP).
• Tshikudi, D. M., Simandoux, O., Kang, D., Yelin, D., Nadkarni, S. K., Cott, E. M., & Andrawes, M. N. (2019). Evaluating fibrin polymerization dynamics in three dimensions peri-operatively in cardiac surgical patients using spectrally encoded confocal microscopy (SECM) (Conference Presentation). In Diagnostic and Therapeutic Applications of Light in Cardiology 2019, 10855.
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  The polymerization dynamics and microstructure of the fibrin network is vital to hemostasis. During cardiac surgery, heparin is administered to prevent bleeding and reversed using protamine at the end of surgery. Residual heparin and inadequate reversal following surgery impair fibrin integrity, likely associated with major postoperative blood loss. In this study, we apply a recent approach, SECM, to evaluate fibrin integrity in blood clots during heparin administration and protamine reversal in cardiac surgery patients. SECM’s capability for video rate microscopy over large fields of view with a spatial resolution of 0.4x1.0µm permits the dynamic assessment of fibrin polymerization and 3D microstructure. Plasma from 10 patients was collected during cardiac surgery at baseline and following protamine reversal. In addition, the dose-dependent response of heparin was studied by spiking 6 normal plasma samples at heparin doses of 0.1-2USP/mL. All samples were tested using SECM and clot polymerization parameters including fibrin time (FT) and fibrin density (FD) were derived. In cardiac surgical patients, FD was lower after protamine reversal (p
• Zhu, W., Pirovano, G., Gong, C., Kulkarni, N., Nguyen, C. D., Brand, C., Reiner, T., & Kang, D. (2019). Smartphone-based epifluorescence microscope for fresh tissue imaging. In Novel Biophotonics Techniques and Applications V.
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  We developed a smartphone-based epifluorescence microscope for fresh tissue imaging. The smartphone microscope optics was optimally designed to achieve similar resolution (0.56 µm) and FOV (520 µm) as the bench 40x microscope, commonly used during the histopathologic analysis. Preliminary images obtained from an excised human pancreatic tissue stained with a rapid staining fluorescence dye (PARPi-FL) clearly visualized individual tumor cells.
• Kang, D. (2018). Spectrally encoded confocal microscopy for comprehensive and low-cost in vivo cellular imaging. In Biophotonics Congress: Biomedical Optics Congress 2018 (Microscopy/Translational/Brain/OTS).
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  In spectrally encoded confocal microscopy (SECM), spectral spread of the imaging light is used to conduct line confocal imaging. Here we present various SECM devices and their uses in clinical applications.
• Kang, D. (2017). In vivo cellular imaging with spectrally encoded confocal microscopy. In Conference on Lasers and Electro-Optics.
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  Spectrally encoded confocal microscopy (SECM) is a high-speed confocal microscopy technique. In this presentation, recent development on endoscopic SECM and smartphone SECM and their uses in in vivo human imaging will be presented.
• Unglert, C., Namati, E., Yoo, H., Liu, L., Kang, D., Tearney, G. J., & Bouma, B. E. (2010). High Resolution Reflectance Microscopy Techniques For 3-Dimensional Imaging Of The Alveolar Structure. In D99. THE FUTURE IS NOW: ADVANCED IMAGING OF LUNG STRUCTURE AND FUNCTION.
• Kang, D., Suter, M. J., Boudoux, C., Yachimski, P. S., Bouma, B. E., Nishioka, N. S., & Tearney, G. J. (2009). Combined spectrally encoded confocal microscopy and optical frequency domain imaging system. In Endoscopic Microscopy IV, 7172.
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  Spectrally encoded confocal microscopy (SECM) and optical frequency domain imaging (OFDI) are two reflectancebased imaging technologies that may be utilized for high-resolution microscopic screening of internal organs. SECM provides en face images of tissues with a high lateral resolution of 1-2 μm, and a penetration depth of up to 300 μm. OFDI generates cross-sectional images of tissue architecture with a resolution of 10-20 μm and a penetration depth of 1- 2 mm. Since the two technologies yield complementary microscopic information on two different size scales (SECM-cellular and OFDI-architectural) that are commonly used for histopathologic evaluation, their combination may allow for more accurate optical diagnosis. Here, we report the integration of these two imaging modalities in a single bench top system. SECM images of swine small intestine showed the presence of goblet cells, and OFDI images revealed the finger-shaped villous architecture. In clinical study of 9 gastroesophageal biopsies from 8 patients, a diverse set of architectural and cellular features was observed, including squamous mucosa with mild hyperplasia and gastric antral mucosa with gastric pits and crypts. The capability of this multimodality device to enable the visualization of microscopic features on these two size scales supports our hypothesis that improved diagnostic accuracy may be obtained by merging these two technologies into a single instrument.
• Kim, J., Kang, D., Cho, H., Sohn, Y. S., & Gweon, D. (2005). Design of real-time confocal microscopy using spectral encoding technique and slit aperture. In Optomechatronic Sensors and Instrumentation, 6049.
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  New confocal microscopy having no mechanical beam scanning devices is proposed. The proposed system can get two-dimensional information of a specimen in real-time by using spectral encoding technique and slit aperture. Spectral encoding technique is used to encode one- dimensional lateral information of the specimen in wavelength by a diffraction grating and a broadband light source. The modeling of the optical system is conducted. The effect of slit width variation on the axial response of the system is evaluated by numerical simulation based on the wave optics. Proper width of the slit aperture which plays a crucial role of the out-of-focus blur rejection is determined by a compromise between axial resolution and signal intensity from the simulation result. Design variables and governing equations of the system are derived on the assumption of a lateral sampling resolution of 50 nm. The system is designed to have a mapping error less than the half pixel size, to be diffraction-limited and to have the maximum illumination efficiency. The designed system has a FOV of 12.8 μm x 9.6 μm, a theoretical axial FWHM of 1.1 μm and a lateral magnification of -367.8.
• Kang, D. K., Seo, J., & Gweon, D. G. (2002). Reflecting optical system to increase signal intensity in confocal microscopy. In Optical Design and Testing, 4927, 396-403.
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  In fluorescence mode confocal microscopes, only 0.02% of emitted signal can be detected in best case. So, we proposed reflecting optical system to increase signal intensity detected in photon detector. In this paper, we evaluate the proposed reflecting optical system using optical transfer function. To evaluate the proposed system, we used the modeling method based on wave optics. We first calculated point spread function of total system, and calculated optical transfer function of total system. When we use the proposed reflecting optical system, we can increase the signal intensity detected in photon detector. Amount of increased signal intensity depends on the ratio of NA of objective in the original confocal microscopy to NA of objective in reflecting optical system. We also simulated axial response of total system. FWHM of axial response increased a little when using reflecting optical system. The amount of increased FWHM also depends on the ratio of NA, mentioned above. Maximum increase in FWHM of axial response is about 5%.
• Lee, J. H., Yoon, H. K., Kang, D. K., Lee, S. T., & Gweon, D. G. (2002). New focusing lens system and tolerance analysis for near field recording system. In Advanced Optical Storage Technology, 4930, 359-366.
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  Tolerance analysis for focusing unit of near field recording system is presented. The assembling and manufacturing tolerances of SIL and OL are simulated using CODE V. In addition, we proposed to move collimated lens (CL) back and forth to compensate and control these tolerances, especially in optical axis direction. And we proposed, a new doublet solid immersion lens (DSIL) for near field optical system, which can minimize the tilting, decenter, defocus misalignment problems between objective lens and solid immersion lens in existing near field optical system. The objective lens, which confines the beam, and secondary lens which increases the numerical aperture, join together to make one module cemented lens system.
• Kang, D. K., Seo, J. W., Park, S. L., & Gweon, D. G. (2001). 3D image reconstruction using optical sectioning in confocal scanning microscopy. In Optomechatronic Systems II, 4564, 58-65.
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  Confocal scanning microscopy (CSM) has been used in biological application, materials science, semiconductor quality measurement and other non-destructive microscopic application. Small spot of light illuminates a sample, and a small detector that is ideally a point detector collects the reflected or transmitted light having the information of specimen. An image distribution can be reconstructed by a correlation analysis of spots with the high bandwidth. The mechanism for two-dimensional beam scanning and optical sectioning has an important role in CSM as the three-dimensional profiler. The parasitic motion of focus on the detector gives rise to the fatal distortion of an image profile named the extinction effect while using acousto-optical (AO) deflector. The intensity profile for the open loop scanning should be matched with its response for the standard. The non-linearity can be minimized with the optical sectioning or the optical probe of the closed loop control. This paper shows the mathematical expression of the light such as the extinction curve in the optical fields of system using AO deflector, the axial/lateral response experimentally when the error sources change, and the methods of optical sectioning. We propose the progressive methods for the high quality image as the following. At first, for having the corrected image, small spot and long scan range, this paper shows that the optimal design having the multi-objects can be used by choosing the unitary lens device in CSM. At second, in order to compensate for the intensity cancellation at the end profile that may be the cause of waviness for the optical image, this paper shows that it is efficient to schedule the frequency of scan. According to characteristics of the extinction curve and axial/lateral response having the error property, we can define the frequency and sensitivity of as their robustness. Finally, the axial response gives an important motive for the optical section, and the limit of object depth. The edge enhancement may be a fatal defeat to the reconstruction of image and sensitive to the conditions of specimen such as slope, irregular reflectivity, shape, etc. That means that the intensity profile for the open loop scanning method should be matched with its response to a perfect mirror as specimen, which can be minimized with the optical sectioning or the optical probe of the closed loop control.
• Park, S., Jung, J., Seo, J., Kang, D. K., & Gweon, D. G. (2001). Auto-alignment for incident angle of ellipsometer. In Optomechatronic Systems II, 4564, 339-347.
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  In this paper, we present a 3-step auto-alignment algorithm for the incident angle of an ellipsometer without auxiliary equipment. The 3-step algorithm uses only a 3-axis precision stage (two rotation and one translation) for ellipsometric incident angle alignment, and consists of two incident angles and its following corrective process. The corrective process is to position the spot on the center of the detector's aperture plane, and consists of accessing and centering on the detector's aperture. In the first step, the polarizer and analyzer arm are set at a proper incident angle and the spot is centered on the detector's aperture by the corrective process. In the second step, the polarizer and analyzer arm are set at a measured incident angle and the spot is centered on the detector's aperture by the corrective process. In the third step, height error and angle errors of the specimen are calculated with the stage's angle from the first and second steps. Finally, locating the specimen stage at an errorless position completes incident angle alignment. We modeled 3-D optical paths using a homogeneous transformation matrix (HTM), and simulated the developed alignment algorithm. The results showed that the developed alignment algorithm works well. Experiment results also revealed good agreement on the simulation. The developed alignment algorithm may be applied to other alignment problems, such as tilt alignment of lithography.

Presentations

• Kang, D. (2020, April). Cellular Imaging of the Cornea with a Low-Cost, Portable Confo- cal Microscope. OSA Biophotonics Congress. Virtual: OSA.
• Kang, D. (2020, February). Speckle-free, spectrally-encoded confocal microscopy. Photonics West. San Francisco: SPIE.
• Kang, D. (2020, September). Miniature, hyperchromatic objective lens for chromatic confocal endomicroscope. IEEE Photonics Conference. Virtual.
• Kang, D. (2019, April). Light sheet microscopy of human skin in vivo. OSA Biophotonics Congress.
• Kang, D. (2019, April). Low-cost, high-speed near-infrared confocal microscope. OSA Biophotonics Congress.
• Kang, D. (2019, February). Artifact correction and automated eosinophil counting for SECM tethered capsule endomicroscopy. Photonics West.
• Kang, D. (2019, February). Evaluating fibrin polymerization dynamics in three dimensions peri-operatively in cardiac surgical patients using spectrally encoded confocal microscopy (SECM). Photonics West.
• Kang, D. (2019, February). High-speed spectrally encoded confocal microscopy (SECM) using 100-kHz swept source laser. Photonics West.
• Kang, D. (2019, February). Implementation of a Portable Confocal Microscope to Diagnose Kaposi’s Sarcoma: The Challenge of Point-of-Care Diagnostics for Skin of Color in Low Resource Settings. Skin of Color Society (SOCS) 15th Annual Scientific Symposium.
• Kang, D. (2019, February). Low-cost, smartphone confocal microscope. Photonics West.
• Kang, D. (2019, February). Preclinical swine joint imaging using forward-viewing spectrally encoded endoscopy. Photonics West.
• Kang, D. (2019, February). Probe-based video-rate color forward-view spectrally encoded endoscopy,. Photonics West.
• Kang, D. (2019, February). Smartphone confocal microscopy for imaging Kaposi’s sarcoma in low-resource settings. Photonics West.
• Kang, D. (2019, June). NOVEL POINT OF CARE DIAGNOSTIC STRATEGIES FOR SKIN DISEASE IN LOW RESOURCE SETTINGS: PORTABLE CONFOCAL MICROSCOPY FOR KAPOSI’S SARCOMA. 24th World Congress of Dermatology.
• Kang, D. (2019, May). AUTOMATED DIAGNOSIS OF EOSINOPHILIC ESOPHAGITIS FROM LARGE IMAGES OBTAINED BY SPECTRALLY-ENCODED TETHERED CAPSULE REFLECTANCE ENDOMICROSCOPY. Digestive Diseases Week.
• Kang, D. (2019, September). High-speed blood flow imaging with scanless confocal microscope. IEEE Photonics Conference 2019.
• Freeman, E. E., Semeere, A., Namaganda, P., Martin, J., Gonzalez, S., Peterson, G., Rajadhyaksha, M., Anderson, R. R., Tearney, G. J., & Kang, D. (2018, January). Smartphone confocal microscopy of human skin in vivo. Photonics West.
• Kang, D. (2018, January). Spectrally encoded confocal microscopy for comprehensive and low-cost in vivo cellular imaging. BME seminar.
• Kang, D. (2018, January). Spectrally encoded confocal microscopy for comprehensive and low-cost in vivo cellular imaging. OSC Colloquium.
• Kang, D., Do, D., Grant, C. N., Giddings, S. L., Rosenberg, M., Hesterberg, P. E., Yuan, Q., Garber, J. J., Katz, A. J., & Tearney, G. J. (2018, January). Small SECM endoscopic capsule for imaging human esophagus in vivo. Photonics West.
• Zeidan, A., Do, D., Kang, D., Ikuta, M., & Tearney, G. J. (2018, January). Forward-viewing spectrally encoded endoscopy with angled detection optics. Photonics West.
• Do, D., Kang, D., Ikuta, M., Hyun, C., & Tearney, G. J. (2017, January). Forward-viewing spectrally encoded endoscopy. Photonics West.
• Ikuta, M., Kang, D., Do, D., & Tearney, G. J. (2017, January). Single-fiber approach for color spectrally encoded endoscopy. Photonics West.
• Kang, D. (2017, May). In vivo Cellular Imaging with Spectrally Encoded Confocal Microscopy. Conference on Lasers and Electro-Optics (CLEO).
• Kang, D., Kim, M., Do, D., Grant, C. N., Rosenberg, M., Nishioka, N. S., & Tearney, G. J. (2017, January). In vivo imaging of human esophagus with SECM half-inch tethered endoscopic capsule. Photonics West.
• Kang, D., Tabatabaei, N., Do, D., & Tearney, G. J. (2017, January). Clinical experience with spectrally encoded confocal microscopy for imaging human esophagus in vivo. Photonics West.

Poster Presentations

• Kang, D. (2019, November). Low-cost confocal microscopy for point-of-care cellular morphologic imaging in vivo. NIH-IEEE Health Innovations Point-of-care Technology.
• Freeman, E. E., Semeere, A., Namaganda, P., Laker-Oketta, M., Lukande, R., Tearney, G. J., Gonzalez, S., Rajadhyaksha, M., Anderson, R. R., Martin, J., & Kang, D. (2017, July). Portable Confocal Microscopy as a Diagnostic Tool for Kaposi’s Sarcoma in Africa. International Conference on Malignancies in HIV/AIDS (ICMH).