Intraocular islet transplantation was investigated as a new procedure to treat diabetes. The development of this procedure requires close monitoring of the function of both eye and islet graft. We developed a soft, smart contact lens to monitor the intraocular pressure and applied this for noninvasive monitoring in association with the intraocular islet transplantation in diabetes. A strain sensor inside the lens can detect detailed changes in intraocular pressure by focusing the strain only in the desired, selective area of the contact lens. In addition, this smart contact lens can transmit the real-time value of the intraocular pressure wirelessly using an antenna. The wireless measurement of intraocular pressure that was obtained using this contact lens had a high correlation with the intraocular pressure measured by a rebound tonometer, thereby proving the good accuracy of the contact lens sensor. In the initial period, a slight elevation of intraocular pressure was observed, but the pressure returned to normal in the initial period after the transplantation. This type of monitoring will provide important information on potential changes in the intraocular pressure associated with the transplantation procedure, and it enables appropriate clinical safety steps to be taken, if needed.
Background and Objectives Precise determination of cancer margin during skin cancer surgery is crucial for complete resection and further clinical prognosis. Although reflection confocal microscopy (RCM) has been used for perioperative guiding, its reflection contrast has limitations in detecting cancer cells in the dermis. We previously developed combined reflection confocal (RC) and moxifloxacin‐based two‐photon (MB‐TP) microscopy for sensitive cancer detection by using multiple contrast mechanisms. In this study, the performance of combined microscopy was characterized in various skin cancer specimens and compared with standard methods. Materials and Methods Seven human skin specimens in total including two normal ones, three basal cell carcinomas (BCCs), and two squamous cell carcinomas (SCCs) were collected and imaged in fresh condition. Moxifloxacin ophthalmic solution was topically instilled for cell labeling for 3–5 minutes, then mosaic imaging with the combined microscopy was conducted. The imaged specimens were imaged again after exogenous nuclear labeling for comparison and then processed for standard hematoxylin and eosin histology. Results Combined RC and MB‐TP microscopy visualized both cell and extracellular matrix structures of the skin specimens with multiple contrasts of reflection, moxifloxacin fluorescence, autofluorescence, and second harmonic generation. It distinguished normal cell structures in the skin dermis such as hair follicles, sebaceous and eccrine glands from BCC nests, and SCCs based on cell organization. Normal cell structures had organized cell arrangements for their functions, while cancer cell structures had dense and disorganized cell arrangements. Cellular features found by combined microscopy images were confirmed by both TP microscopy with nuclear labeling and histological examination. Conclusions The imaging results showed the potential of combined microscopy for sensitive cancer detection and in vivo guiding of skin cancer surgery.
Delineation of brain tumor margins during surgery is critical to maximize tumor removal while preserving normal brain tissue to obtain optimal clinical outcomes. Although various imaging methods have been developed, they have limitations to be used in clinical practice. We developed a high‐speed cellular imaging method by using clinically compatible moxifloxacin and confocal microscopy for sensitive brain tumor detection and delineation. Moxifloxacin is a Food and Drug Administration (FDA) approved antibiotic and was used as a cell labeling agent through topical administration. Its strong fluorescence at short visible excitation wavelengths allowed video‐rate cellular imaging. Moxifloxacin‐based confocal microscopy (MBCM) was characterized in normal mouse brain specimens and visualized their cytoarchitecture clearly. Then, MBCM was applied to both brain tumor murine models and two malignant human brain tumors of glioblastoma and metastatic cancer. MBCM detected tumors in all the specimens by visualizing dense and irregular cell distributions, and tumor margins were easily delineated based on the cytoarchitecture. An image analysis method was developed for automated detection and delineation. MBCM demonstrated sensitive delineation of brain tumors through cytoarchitecture visualization and would have potentials for human applications, such as a surgery‐guiding method for tumor removal.
Pancreatic islets regulate glucose homeostasis in the body, and their dysfunction is closely related to diabetes. Islet transplantation into the anterior chamber of the eye (ACE) was recently developed for both in vivo islet study and diabetes treatment. Optical coherence microscopy (OCM) was previously used to monitor ACE transplanted islets in non-obese diabetic (NOD) mice for detecting autoimmune attack. In this study, OCM was applied to streptozotocin (STZ)-induced diabetic mouse models for the early detection of islet damage. A custom extended-focus OCM (xfOCM) was used to image islet grafts in the ACE longitudinally during STZ-induced beta cell destruction together with conventional bright-field (BF) imaging and invasive glucose level measurement. xfOCM detected local structural changes and vascular degradation during the islet damage which was confirmed by confocal imaging of extracted islet grafts. xfOCM detection of islet damage was more sensitive than BF imaging and glucose measurement. Longitudinal xfOCM images of islet grafts were quantitatively analyzed. All these results showed that xfOCM could be used as a non-invasive and sensitive monitoring method for the early detection of deficient islet grafts in the ACE with potential applications to human subjects.
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