Real Time Full-Color Imaging in a Meta-Optical Fiber Endoscope

Endoscopes are an important component for the development of minimally invasive surgeries. Their size is one of the most critical aspects, because smaller and less rigid endoscopes enable higher agility, facilitate larger accessibility, and induce less stress on the surrounding tissue. In all existing endoscopes, the size of the optics poses a major limitation in miniaturization of the imaging system. Not only is making small optics difficult, but their performance also degrades with downscaling. Meta-optics have recently emerged as a promising candidate to drastically miniaturize optics while achieving similar functionalities with significantly reduced size. Herein, we report an inverse-designed meta-optic, which combined with a coherent fiber bundle enables a 33% reduction in the rigid tip length over traditional gradient-index (GRIN) lenses. We use the meta-optic fiber endoscope (MOFIE) to demonstrate real-time video capture in full visible color, the spatial resolution of which is primarily limited by the fiber itself. Our work shows the potential of meta-optics for integration and miniaturization of biomedical devices towards minimally invasive surgery

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Missing the mark: is ICS training achieving its goal?

The Incident Command System (ICS) was originally adopted in the 1970s as a fire service emergency management system. Following the events on September 11, 2001, the National Response Plan adopted ICS across all hazards and disciplines in order to unite responders under the same management system during emergencies. However, creating one system to service so many disparate agencies and response types was a massive undertaking, and the system's effectiveness has since been questioned. To operate in ICS, responders must engage in the adult learning process, which requires social interaction with an engaged instructor and active peers. Before the system can be judged properly, we must ensure personnel have been trained and are implementing the system adequately. This thesis examines the adult learning process and the keys to ensuring that learning and behavior change actually occur. It further examines ICS courses' current online delivery system and recommends evaluating this system to engage the social learning required for successful cultural change. The thesis also critiques the ICS training measurement method and recommends changes to better measure system learning and utilization.http://archive.org/details/missingmarkisics1094551614Assistant Chief, Point Pleasant Fire Protection District, Boone County, KentuckyApproved for public release; distribution is unlimited

Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo

We present a small, lightweight two-photon fiberscope and demonstrate its suitability for functional imaging in the intact brain. Our device consists of a hollow-core photonic crystal fiber for efficient delivery of near-IR femtosecond laser pulses, a spiral fiber-scanner for resonant beam steering, and a gradient-index lens system for fluorescence excitation, dichroic beam splitting, and signal collection. Fluorescence light is remotely detected using a standard photomultiplier tube. All optical components have 1 mm dimensions and the microscope’s headpiece weighs only 0.6 grams. The instrument achieves micrometer resolution at frame rates of typically 25 Hz with a field-of-view of up to 200 microns. We demonstrate functional imaging of calcium signals in Purkinje cell dendrites in the cerebellum of anesthetized rats. The microscope will be easily portable by a rat or mouse and thus should enable functional imaging in freely behaving animals

A Shared-Aperture Tracking Display for Augmented Reality”, Presence: Teleoperators and Virtual Environments

The operation and performance of a six degree-of-freedom (DOF) shared-aperture tracking system with image overlay is described. This unique tracking technology shares the same aperture or scanned optical beam with the visual display, Virtual Retinal Display (VRD). This display technology provides high brightness in an AR helmet mounted display, especially in the extreme environment of a military cockpit. The VRD generates an image by optically scanning visible light directly to the viewer’s eye. By scanning both visible and infrared light, the head-worn display can be directly coupled to a head tracking system. As a result, the proposed tracking system requires minimal calibration between the user’s viewpoint and the tracker’s viewpoint. This paper demonstrates that the proposed shared-aperture tracking system produces high accuracy and computational efficiency. The current proof-of-concept system has a precision of +/-0.05 and +/- 0.01 degrees in the horizontal and vertical axes respectively. The static registration error was measured to be 0.08 +/-0.04 and 0.03 +/- 0.02 degrees for the horizontal and vertical axes respectively. The dynamic registration error or the system latency was measured to be within 16.67ms, equivalent to our display refresh rate of 60 Hz. In all testing, the VRD was fixed and the calibrated motion of a robot arm was tracked during. By moving the robot arm within a restricted volume, this real-time shared-aperture method of tracking was extended to 6 DOF measurements. Future AR applications of our shared-aperture tracking and display system will be highly-accurate head tracking when the VRD is helmet-mounted and worn within an enclosed space, such as an airplane cockpit. 1

Method to Achieve High Frame Rates in a Scanning Fiber Endoscope

A new and miniature imaging device is being developed to allow flexible endoscopy in regions of the body that are difficult to reach. The scanning fiber endoscope employs a single scanning optical fiber to illuminate a target area, while backscattered light is detected one pixel at a time to build a complete image. During each imaging cycle the fiber is driven outward in a spiral pattern from its resting state at the image center to the outer fringe of the image. At this point, the fiber is quickly driven back to its initial position before acquiring a subsequent frame. This work shortens the time between successive images to achieve higher overall frame rates by applying a carefully timed input, which counteracts the tip motion of the scanning fiber, quickly forcing the scanning fiber to the image center. This input is called motion braking and is a square wave function dependent upon the damped natural frequency of the scanning fiber and the instantaneous tip displacement and velocity. Imaging efficiency of the scanning fiber endoscope was increased from 75-89% with this implementation