Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis.

Genomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the in-situ higher-order folding of chromatin structure during malignant transformation remains largely unknown. Here, using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncover a gradual decompaction and fragmentation of higher-order chromatin folding throughout all stages of carcinogenesis in multiple tumor types, and prior to tumor formation. Our integrated imaging, genomic, and transcriptomic analyses reveal functional consequences in enhanced transcription activities and impaired genomic stability. We also demonstrate the potential of imaging higher-order chromatin disruption to detect high-risk precursors that cannot be distinguished by conventional pathology. Taken together, our findings reveal gradual decompaction and fragmentation of higher-order chromatin structure as an enabling characteristic in early carcinogenesis to facilitate malignant transformation, which may improve cancer diagnosis, risk stratification, and prevention.

Real-time dual-modal vein imaging system.

PURPOSE: In this paper, we present a vein imaging system to combine reflectance mode visible spectrum images (VIS) with transmission mode near-infrared (NIR) images in real time. Clear vessel localization is achieved in this manner with combined NIR-VIS dual-modal imaging. METHODS: Transmission and reflectance mode optical instrumentation is used to combine VIS and NIR images. Two methods of displaying the combined images are demonstrated here. We have conducted experiments to determine the system's resolution, alignment accuracy, and depth penetration. Vein counts were taken from the hands of test subjects using the system and compared with vein counts taken by visual analysis. RESULTS: Results indicate that the system can improve vein detection in the human hand while detecting veins of a diameter < 0.5 mm at any working distance and of a 0.25 mm diameter at an optimal working distance of about 30 cm. The system has also been demonstrated to clearly detect silicone vessels with artificial blood of diameter 2, 1, and 0.5 mm diameter under a tissue depth of 3 mm. In a study involving 25 human subjects, we have demonstrated that vein visibility was significantly increased using our system. CONCLUSIONS: The results indicate that the device is a high-resolution solution to near-surface venous imaging. This technology can be applied for IV placement, morphological analysis for disease state detection, and biometric analysis.

Intraoperative Fluorescence Imaging and Multimodal Surgical Navigation Using Goggle System.

Intraoperative imaging is an invaluable tool in many surgical procedures. We have developed a wearable stereoscopic imaging and display system entitled Integrated Imaging Goggle, which can provide real-time multimodal image guidance. With the Integrated Imaging Goggle, wide field-of-view fluorescence imaging is tracked and registered with intraoperative ultrasound imaging and preoperative tomography-based surgical navigation, to provide integrated multimodal imaging capabilities in real-time. Herein we describe the system instrumentation and the methods of using the Integrated Imaging Goggle to guide surgeries.

Stereoscopic Integrated Imaging Goggles for Multimodal Intraoperative Image Guidance.

We have developed novel stereoscopic wearable multimodal intraoperative imaging and display systems entitled Integrated Imaging Goggles for guiding surgeries. The prototype systems offer real time stereoscopic fluorescence imaging and color reflectance imaging capacity, along with in vivo handheld microscopy and ultrasound imaging. With the Integrated Imaging Goggle, both wide-field fluorescence imaging and in vivo microscopy are provided. The real time ultrasound images can also be presented in the goggle display. Furthermore, real time goggle-to-goggle stereoscopic video sharing is demonstrated, which can greatly facilitate telemedicine. In this paper, the prototype systems are described, characterized and tested in surgeries in biological tissues ex vivo. We have found that the system can detect fluorescent targets with as low as 60 nM indocyanine green and can resolve structures down to 0.25 mm with large FOV stereoscopic imaging. The system has successfully guided simulated cancer surgeries in chicken. The Integrated Imaging Goggle is novel in 4 aspects: it is (a) the first wearable stereoscopic wide-field intraoperative fluorescence imaging and display system, (b) the first wearable system offering both large FOV and microscopic imaging simultaneously,