<p>Supplementary Video S1 shows a Keratin Pearl. Keratin pearls are often present in oral squamous cell carcinoma (OSCC). They are composed of concentric rings of squamous cells showing gradual keratinization.</p>
<p>Supplementary Figure S11 shows in vivo RCM images of a tumor in a 26-year-old male, with no history of tobacco or alcohol exposure. The patient harbored a 2.0 cm poorly differentiated oral squamous cell carcinoma on the right lateral tongue.</p>
<p>Supplementary Figure S5 shows in vivo RCM images of a tumor area in an 84-year-old female patient, with a history of 2 packs of cigarettes per day for 65 years and no history of alcohol exposure, harboring a 3.2-cm infiltrating moderately differentiated oral squamous cell carcinoma of the right lateral tongue.</p>
Confocal microscopy is in clinical use to diagnose skin cancers in the United States and in Europe. Potentially, this technology may provide bed-side pathology in breast cancer surgery during tumor removal. Initial studies have described major findings of invasive breast cancers as seen on fluorescence confocal microscopy. In many of these studies the region of interest (ROI) used in the analysis was user-selected and small (typically 15 square-mm). Although these important findings open exploration into rapid pathology, further development and implementation in a surgical setting will require examination of large specimens in a blinded fashion that will address the needs of typical surgical settings. In post surgery pathology viewing, pathologists inspect the entire pathology section with a low (2X) magnification objective lens initially and then zoomed in to ROIs with higher magnification lenses (10X to 40X) magnifications to further investigate suspected regions. In this study we explore the possibility of implementation in a typical surgical setting with a new microscope, termed confocal strip-mosaicking microscope (CSM microscope), which images an area of 400 square-mm (2 cm x 2 cm) of tissue with cellular level resolution in 10 minutes. CSM images of 34 human breast tissue specimens from 18 patients were blindly analyzed by a board-certified pathologist and correlated with the corresponding standard fixed histopathology. Invasive tumors and benign tissue were clearly identified in CSM images. Thirty specimens were concordant for images-to-histopathology correlation while four were discordant. Preliminary results from on-going work to molecularly target tumor margin will also be presented.
Handheld and endoscopic optical-sectioning microscopes are being developed for noninvasive screening and intraoperative consultation. Imaging a large extent of tissue is often desired, but miniature in vivo microscopes tend to suffer from limited fields of view. To extend the imaging field during clinical use, we have developed a real-time video mosaicking method, which allows users to efficiently survey larger areas of tissue. Here, we modified a previous post-processing mosaicking method so that real-time mosaicking is possible at >30 frames/second when using a device that outputs images that are 400 × 400 pixels in size. Unlike other real-time mosaicking methods, our strategy can accommodate image rotations and deformations that often occur during clinical use of a handheld microscope. We perform a feasibility study to demonstrate that the use of real-time mosaicking is necessary to enable efficient sampling of a desired imaging field when using a handheld dual-axis confocal microscope.
We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo 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. In vivo 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 in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging.