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Label-free optical imaging techniques for digital histopathology

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The histological examination of excised tissue via optical microscope has been widely used in biological laboratory and clinic. Although histopathology is a gold-standard to understand tissue morphology, to diagnose diseases, and to decide treatment course, it is very time- and labor-intensive and has limitation to visualize pathologic features over large areas in quantitative fashion. To address this limitation, we have developed several multi-scale optical imaging approaches that are stain‐independent, high‐throughput and quantitative. The ultimate objective of research is to demonstrate new protocol of digital histopathology based on AI-driven high resolution and sparse optical imaging.

  • Serial optical coherence microscopy for label-free volumetric histopathology, Scientific Reports, 2020  [PDF] 

  • Effect of tissue staining in quantitative phase imaging, Journal of Biophotonics, 2018  [PDF]

  • Wide-field optical coherence microscopy of the mouse brain slice, Optics Letters, 2015  [PDF]

Optical neuronal stimulation and comprehensive interpretation of massive data

The electrophysiological technology has made tremendous contributions to understanding neuronal dynamics and connectivity, through recording real-time intracellular and extracellular activities from excitable neurons during stimulation responses. Although valuable information can be obtained by currently available methods, there is still a technical challenge when dealing with non-invasive neuronal stimulation, massive data collection, experimental reproducibility, and automated comprehensive interpretation of neuronal activities. In order to address these limitations, we have revised optical stimulation techniques with theoretical modeling, and comprehensive read-out for wide-range and multi-neuronal activities.

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  • Image-guided recording system for spatial and temporal mapping of neuronal activities in brain slice, Journal of Biophotonics, 2018  [PDF]

  • Label-free, multi-scale imaging of ex-vivo mouse brain using spatial light interference microscopy, Scientific Reports, 2016  [PDF]

  • One-photon and two-photon stimulation of neurons in a microfluidic culture systemLab on a Chip, 2016  [PDF]

Mobile-based medical device toward digital medicine

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The use of mobile device including smartphone as portable medical device has opened new opportunities for offering advanced diagnostic protocols through telemedicine and big data analysis. The most unique signatures of mobile medical device include low cost, mobility, flexibility, and data sharing which are largely absent from conventional medical devices. In particular, mobile medical device would be very useful when primary diagnostics has limited applicability due to the lack of infrastructure or when the fast screening information of patients is required. Our group have developed a mobile diagnostic platform integrated with AI algorithm which enables providing inexpensive, reliable, and accurate measurement for futuristic medical services without spatial constraint.

  • Quantitative screening of cervical cancers for low-resource settings: Pilot study of smartphone-based endoscopic VIA using machine learning technique, JMIR mHealth and uHealth, 2020  [PDF]

  • Smartphone-based endoscope system for advanced point-of-care diagnostics: Feasibility study, JMIR mHealth and uHealth, 2017  [PDF]

High-resolution 3D tissue scanner for advanced tissue engineering

The bio-printing has received growing interest as it is widely used for broad-spectrum applications such as regenerative medicines, tissue engineering and transplantation. Our group is currently trying to transform the near infrared optical imaging technology as novel optical scanner for accurate bio-printing. Unique feature of our scanner over conventional bio-scanner including CT is its capability to provide the high-resolution and volumetric tissue information. The process of bio-printing implemented with new optical scanner can offer the customized transplantation materials, enabling personalized tissue engineering. This new approach would be initially applied to fabricate relatively thin tissues such as skin, cornea and tympanic membrane.

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  • Quantitative evaluation of skin surface roughness using optical coherence tomography in vivo, IEEE Journal of Selected Topics in Quantum Electronics, 2019  [PDF]

  • Quantitative monitoring of laser-treated engineered skin using optical coherence tomography, Biomedical Optics Express, 2016  [PDF]

Intelligent optical imaging system for high-throughput phenotype screening

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Phenotype-based screening for drug discovery is increasingly employed in biomedical and pharmaceutical research. Recently, the zebrafish model has emerged as the main vertebrate model system due to its versatility and short life span. Thus, it would be very powerful model for high-throughput and high-content chemical screening experiments and large-scale phenotypic scoring. In particular, whole zebrafish in vivo approaches have the advantage that they can reveal toxicity and other side-effects of drugs at a very early stage of the study. Our engineering solution is to implement the in-line monitoring device like an office scanner combined with AI-based algorithm which enables sequentially observing large number of whole zebrafish as well as offering the quantitative phenotype information.

  • Label‐free optical projection tomography for quantitative three‐dimensional anatomy of mouse embryo, Journal of Biophotonics, 12:e201800481, 2019  [PDF]

Probe-based imaging techniques for non-invasive optical biopsy

In conventional pathology, histological examination of the tissue is considered the “gold standard” for diagnosing various diseases. It has contributed significantly toward identifying the abnormalities in tissues and cells, but has inherent drawbacks when used for fast and accurate diagnosis. Our group has constructed the probe-based optical technique for non-invasive and real-time optical biopsy by leveraging the state-of-the-art tools including deep-tissue optical imaging system, fiber-optics, and MEMS technologies. Our devices are specifically designed for the clinical environment and integrate with various optical   imaging probes such as endoscope, surgical microscope, and handheld scanner for specific targeted application.

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  • Lamellar keratoplasty using position-guided surgical needle and M-mode optical coherence tomography, Journal of Biomedical Optics,  2017  [PDF]

  • Handheld Optical Coherence Tomography Scanner for Primary Care Diagnostics, IEEE Transaction on Biomedical Engineering, 2011  [PDF]

  • Miniaturized probe based on a microelectromechanical system mirror for multiphoton microscopy, Optics Letters, 2008  [PDF]

  • In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror, Optics Letters,  2007  [PDF]

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