Fluorescence guided surgery has high potential for improved patient outcomes but often lacks quantification of fluorophore depth which is needed to determine surgical margins of solid tumors. To address this need, a dual wavelength excitation approach was applied that capitalizes on the wavelength-dependent attenuation of light in tissue to provide depth information independent of fluorophore concentration. A portable near infrared dual wavelength excitation fluorescence imaging system was built and tested using tissue mimicking phantoms and is currently being tested to determine breast tumor margin status in a first-in-human clinical trial investigating LS301, a novel near infrared tumor-targeted contrast agent.
LS301 is a promising NIR fluorescence probe for targeting brain glioma cancer. The co-localization of LS31 and 5-ALA induced PpIX in vitro and in vivo enables LS301 to guide PpIX fluorescence image surgery. Moreover, LS301 showed no negative impact on 5-ALA-PpIX PDT outcome in brain glioma cells and mouse tumor model. Therefore, the implementation of LS301 and PpIX has potential to improve tumor resection surgery and PDT treatment for better tumor outcomes.
KEYWORDS: Cancer, Tissues, Thermography, Tumor growth modeling, Thermal modeling, Tumors, 3D modeling, Thermal energy technology, Systems modeling, Real time imaging
Dynamic thermal imaging has improved bulk tissue characterization, but fails to capture subtle thermal property differences in heterogeneous systems. We present focal dynamic thermal imaging (FDTI), a simple, label-free, and high-resolution technology for delineating tissue heterogeneity. Stimulation of focal regions of absorptive materials with a narrow beam, low power, and low cost 405 nm laser locally perturbs the thermal equilibrium. Measurement of phantoms, ex vivo tissue, and in vivo animal models of cancer reveals finite structures of materials and delineates diseased from healthy tissue. Portable FDTI holds promise to capture the heterogeneous nature of malignant tissue.
Inspired by the visual system of the morpho butterfly, we have designed, fabricated, tested and clinically translated an ultra-sensitive, light weight and compact imaging sensor capable of simultaneously capturing near infrared (NIR) and visible spectrum information. The visual system of the morpho butterfly combines photosensitive cells with spectral filters at the receptor level. The spectral filters are realized by alternating layers of high and low dielectric constant, such as air and cytoplasm. We have successfully mimicked this concept by integrating pixelated spectral filters, realized by alternating silicon dioxide and silicon nitrate layers, with an array of CCD detectors. There are four different types of pixelated spectral filters in the imaging plane: red, green, blue and NIR. The high optical density (OD) of all spectral filters (OD>4) allow for efficient rejections of photons from unwanted bands. The single imaging chip weighs 20 grams with form factor of 5mm by 5mm.
The imaging camera is integrated with a goggle display system. A tumor targeted agent, LS301, is used to identify all spontaneous tumors in a transgenic PyMT murine model of breast cancer. The imaging system achieved sensitivity of 98% and selectivity of 95%. We also used our imaging sensor to locate sentinel lymph nodes (SLNs) in patients with breast cancer using indocyanine green tracer. The surgeon was able to identify 100% of SLNs when using our bio-inspired imaging system, compared to 93% when using information from the lymphotropic dye and 96% when using information from the radioactive tracer.
A wearable all-plastic imaging system for real-time fluorescence image-guided surgery is presented. The compact size of the system is especially suitable for applications in the operating room. The system consists of a dual-mode imaging system, see-through goggle, autofocusing, and auto-contrast tuning modules. The paper will discuss the system design and demonstrate the system performance.
Near-infrared (NIR) fluorescent imaging system has been widely used for intraoperative image-guided application. In
this paper, we present performance comparison from three compact NIR fluorescence imaging system prototypes with
goggle display that we developed for intraoperative guidance: threshold detection based two camera system, feature
matching based three cameras system and miniature beam-splitter single camera system. Their performance is evaluated
according to sensitivity regarding different ICG concentrations, accuracy of image overlay between NIR-visible
channels, compactness and practicability in intraoperative use. The comparison results show great potentials of using
these NIR fluorescence imaging systems to improve user experience and surgical outcomes in intraoperative use.
Near infrared (NIR) fluorescence imaging has shown great potential for various clinical procedures, including intraoperative image guidance. However, existing NIR fluorescence imaging systems either have a large footprint or are handheld, which limits their usage in intraoperative applications. We present a compact NIR fluorescence imaging system (NFIS) with an image overlay solution based on threshold detection, which can be easily integrated with a goggle display system for intraoperative guidance. The proposed NFIS achieves compactness, light weight, hands-free operation, high-precision superimposition, and a real-time frame rate. In addition, the miniature and ultra-lightweight light-emitting diode tracking pod is easy to incorporate with NIR fluorescence imaging. Based on experimental evaluation, the proposed NFIS solution has a lower detection limit of 25 nM of indocyanine green at 27 fps and realizes a highly precise image overlay of NIR and visible images of mice in vivo. The overlay error is limited within a 2-mm scale at a 65-cm working distance, which is highly reliable for clinical study and surgical use.
The near-infrared (NIR) fluorescence signal in the 700 to 900 nm from molecular probes used in fluorescence image-guided surgery (FIGS) is usually weak compared to the NIR component from white light-emitting diode surgical light, which is typically switched off during FIGS to enhance the molecular fluorescence contrast of the image. We propose a simple solution to this critical issue in FIGS by removing NIR light from surgical light with a low cost commercial 3M cool mirror film 330.
We have developed a wearable, fluorescence goggle based system for intraoperative imaging of tumors and image guidance in oncologic surgery. Our system can detect fluorescence from cancer selective near infra-red (NIR) contrast agent, facilitating intraoperative visualization of surgical margins and tumors otherwise not apparent to the surgeon. The fluorescence information is displayed directly to the head mounted display (HMD) of the surgeon in real time, allowing unhindered surgical procedure under image guidance. This system has the potential of improving surgical outcomes in oncologic surgery and reduce the chances of cancer recurrence.
Optical imaging enables real-time visualization of intrinsic and exogenous contrast within biological tissues. Applications in human medicine have demonstrated the power of fluorescence imaging to enhance visualization in dermatology, endoscopic procedures, and open surgery. Although few optical contrast agents are available for human medicine at this time, fluorescence imaging is proving to be a powerful tool in guiding medical procedures. Recently, intraoperative detection of fluorescent molecular probes that target cell-surface receptors has been reported for improvement in oncologic surgery in humans. We have developed a novel system, optical projection of acquired luminescence (OPAL), to further enhance real-time guidance of open oncologic surgery. In this method, collected fluorescence intensity maps are projected onto the imaged surface rather than via wall-mounted display monitor. To demonstrate proof-of-principle for OPAL applications in oncologic surgery, lymphatic transport of indocyanine green was visualized in live mice for intraoperative identification of sentinel lymph nodes. Subsequently, peritoneal tumors in a murine model of breast cancer metastasis were identified using OPAL after systemic administration of a tumor-selective fluorescent molecular probe. These initial results clearly show that OPAL can enhance adoption and ease-of-use of fluorescence imaging in oncologic procedures relative to existing state-of-the-art intraoperative imaging systems.
KEYWORDS: Luminescence, Goggles, Imaging systems, Signal to noise ratio, Near infrared, Signal detection, Liver, Surgery, CMOS technology, Optical sensors
We have developed a near-infrared (NIR) fluorescence goggle system based on the complementary metal–oxide–semiconductor active pixel sensor imaging and see-through display technologies. The fluorescence goggle system is a compact wearable intraoperative fluorescence imaging and display system that can guide surgery in real time. The goggle is capable of detecting fluorescence of indocyanine green solution in the picomolar range. Aided by NIR quantum dots, we successfully used the fluorescence goggle to guide sentinel lymph node mapping in a rat model. We further demonstrated the feasibility of using the fluorescence goggle in guiding surgical resection of breast cancer metastases in the liver in conjunction with NIR fluorescent probes. These results illustrate the diverse potential use of the goggle system in surgical procedures.
We have developed a fluorescence goggle device for intraoperative oncologic imaging. With our system design, the
surgeon can directly visualize the fluorescence information from the eyepieces in real time without any additional
monitor, which can improve one's coordination and surgical accuracy. In conjunction with targeting fluorescent dyes,
the goggle device can successfully detect tumor margins and small nodules that are not obvious to naked eye. This can
potentially decrease the incidence of incomplete resection.
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