Bile duct cancer, or cholangiocarcinoma, is a prevalent liver cancer often diagnosed at advanced stages, leading to poor survival rates. Therefore, the development of a reliable early detection technique is urgently needed. Current imaging techniques lack the necessary accuracy to distinguish between dysplastic and benign biliary ducts. Endoscopic techniques, while capable of directly assessing the bile duct lining, often suffer from insufficient sampling. In this paper we discuss a novel endoscopic optical light scattering technique designed to evaluate the malignant potential of the bile duct. The technique employs an ultraminiature spatial gating fiber optic probe compatible with cholangioscopes and endoscopic retrograde cholangiopancreatography (ERCP) catheters. The miniature optical probe enables the detailed investigation of the internal cellular composition of the bile duct epithelium using light scattering spectroscopy (LSS) and also allows for the assessment of the phenotypic properties of the underlying connective tissue with diffuse reflectance spectroscopy (DRS). In a pilot in vivo double-blind prospective study involving 29 patients undergoing routine ERCP procedures, the technique detected malignant transformation with 97% accuracy. Our pilot study suggests that biliary duct pre-cancer can be identified non-invasively in vivo, offering a promising new avenue for early detection and intervention in bile duct cancer.
Coherent confocal light absorption and scattering spectroscopic (C-CLASS) microscopy, which extends the principles of light scattering spectroscopy to subcellular imaging, can be used to reveal biological structures well beyond the diffraction limit. Here we show that high-resolution C-CLASS microscopy can be used to detect nanoscale changes in chromatin structure. Unlike most methods for chromatin monitoring, C-CLASS microscopy can be used label-free in live cells. Live differentiating hiPSC organoids were measured over the space of sixteen days and characteristic chromatin changes were observed.
The COVID-19 pandemic has caused a marked disruption in the delivery of medical care, resulting in significant negative consequences for patients. Considering Covid-19 spreads primarily through expelled respiratory droplets, the ability to detect and measure droplets is critical to the development of clinical protective practices. However, most available methods are either unsuitable for the clinical setting, or cannot distinguish solid particles from liquid droplets. We developed a robust and portable optical instrument capable of measuring the size and quantity of droplets generated during medical procedures. Here we outline the system design and describe our preclinical measurements, which showed that surgical masks significantly reduce the number of expelled speech droplets.
Nanoscale changes in the nuclear structure have been shown to play a critical role in genetic and transcriptional alterations and are a hallmark of neoplasia. Genomic processes are regulated by chromatin packing density, thus underlying the significance of understanding the subnuclear structure and its role in the regulation of molecular processes. However, the dynamic and multiscale aspects of these phenomena have remained an open problem. The key reason is the lack of technologies for label-free nanoscale-sensitive measurements in live cells. We have developed confocal light absorption and scattering spectroscopic (CLASS) microscopy for label-free chromatin sensing in live cells.
In this talk, we will discuss how scattered light can be used for noninvasive detection of invisible pre-cancer in organs such as the esophagus or pancreas which seem to have little in common. Nevertheless, since pre-cancer in many organs is characterized by certain common microscopic changes in the epithelial cells, such as the increase in nuclear size and nuclear density, we will show that light scattering signatures of those pre-cancers are quite similar, allowing for early cancer imaging and detection without the need for external markers. Light scattering signatures can also be used for sensing subnuclear and subcelluar structures, such as chromatin packing, organelle organization, and characterization of cell-derived exosomes. Nanoscale changes in the nuclear structure have been shown to play a critical role in genetic and transcriptional alterations and are a hallmark of neoplasia. We will discuss how the approach based on the combination of confocal microscopy and spectroscopy
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