Clinical utility of many biomedical optical devices is limited by the lack of effective and traceable calibration methods. Optical phantoms that simulate biological tissues used for optical device calibration have been explored. However, these phantoms can hardly simulate both structural and optical properties of multi-layered biological tissue. To address this limitation, we develop a 3D printing production line that integrates spin coating, light-cured 3D printing and Fused Deposition Modeling (FDM) for freeform fabrication of optical phantoms with mechanical and optical heterogeneities. With the gel wax Polydimethylsiloxane (PDMS), and colorless light-curable ink as matrix materials, titanium dioxide (TiO2) powder as the scattering ingredient, graphite powder and black carbon as the absorption ingredient, a multilayer phantom with high-precision is fabricated. The absorption and scattering coefficients of each layer are measured by a double integrating sphere system. The results demonstrate that the system has the potential to fabricate reliable tissue-simulating phantoms to calibrate optical imaging devices.
As a near-infrared (NIR) fluorescence dye, Indocyanine Green (ICG) has not gained broader clinical applications, owing to its multiple limitations such as concentration-dependent aggregation, low fluorescence quantum yield, poor physicochemical stability and rapid elimination from the body. In the meanwhile, 2H,3H-perfluoropentane (H-PFP) has been widely studied in ultrasound imaging as a vehicle for targeted delivery of contrast agents and drugs. We synthesized a novel dual-modal fluorescence and ultrasound contrast agent by encapsulating ICG and H-PFP in lipid microbubbles using a liquid-driven coaxial flow focusing (LDCFF) process. Uniform microbubbles with the sizes ranging from 1-10um and great ICG loading efficiency was achieved by this method. Our benchtop experiments showed that ICG/H-PFP microbubbles exhibited less aggregation, increased fluorescence intensity and more stable photostability compared to free ICG aqueous solution. Our phantom experiments demonstrated that ICG/H-PFP microbubbles enhanced the imaging contrasts in fluorescence imaging and ultrasonography. Our animal experiments indicated that ICG/H-PFP microbubbles extended the ICG life time and facilitated dual mode fluorescence and ultrasound imaging in vivo.
Surgical resection remains the primary curative intervention for cancer treatment. However, the occurrence of a residual tumor after resection is very common, leading to the recurrence of the disease and the need for re-resection. We develop a surgical Google Glass navigation system that combines near infrared fluorescent imaging and ultrasonography for intraoperative detection of sites of tumor and assessment of surgical resection boundaries, well as for guiding sentinel lymph node (SLN) mapping and biopsy. The system consists of a monochromatic CCD camera, a computer, a Google Glass wearable headset, an ultrasonic machine and an array of LED light sources. All the above components, except the Google Glass, are connected to a host computer by a USB or HDMI port. Wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A control program is written in C++ to call OpenCV functions for image calibration, processing and display. The technical feasibility of the system is tested in both tumor simulating phantoms and in a human subject. When the system is used for simulated phantom resection tasks, the tumor boundaries, invisible to the naked eye, can be clearly visualized with the surgical Google Glass navigation system. This system has also been used in an IRB approved protocol in a single patient during SLN mapping and biopsy in the First Affiliated Hospital of Anhui Medical University, demonstrating the ability to successfully localize and resect all apparent SLNs. In summary, our tumor simulating phantom and human subject studies have demonstrated the technical feasibility of successfully using the proposed goggle navigation system during cancer surgery.
In this paper we proposed a portable fluorescence microscopic imaging system to prevent iatrogenic biliary injuries from occurring during cholecystectomy due to misidentification of the cystic structures. The system consisted of a light source module, a CMOS camera, a Raspberry Pi computer and a 5 inch HDMI LCD. Specifically, the light source module was composed of 690 nm and 850 nm LEDs, allowing the CMOS camera to simultaneously acquire both fluorescence and background images. The system was controlled by Raspberry Pi using Python programming with the OpenCV library under Linux. We chose Indocyanine green(ICG) as a fluorescent contrast agent and then tested fluorescence intensities of the ICG aqueous solution at different concentration levels by our fluorescence microscopic system compared with the commercial Xenogen IVIS system. The spatial resolution of the proposed fluorescence microscopic imaging system was measured by a 1951 USAF resolution target and the dynamic response was evaluated quantitatively with an automatic displacement platform. Finally, we verified the technical feasibility of the proposed system in mouse models of bile duct, performing both correct and incorrect gallbladder resection. Our experiments showed that the proposed system can provide clear visualization of the confluence between the cystic duct and common bile duct or common hepatic duct, suggesting that this is a potential method for guiding cholecystectomy. The proposed portable system only cost a total of $300, potentially promoting its use in resource-limited settings.
Near infrared (NIR) fluorescence imaging technique can provide precise and real-time information about tumor location
during a cancer resection surgery. However, many intraoperative fluorescence imaging systems are based on wearable
devices or stand-alone displays, leading to distraction of the surgeons and suboptimal outcome. To overcome these
limitations, we design a projective fluorescence imaging system for surgical navigation. The system consists of a LED
excitation light source, a monochromatic CCD camera, a host computer, a mini projector and a CMOS camera. A
software program is written by C++ to call OpenCV functions for calibrating and correcting fluorescence images
captured by the CCD camera upon excitation illumination of the LED source. The images are projected back to the
surgical field by the mini projector. Imaging performance of this projective navigation system is characterized in a tumor
simulating phantom. Image-guided surgical resection is demonstrated in an ex-vivo chicken tissue model. In all the
experiments, the projected images by the projector match well with the locations of fluorescence emission. Our
experimental results indicate that the proposed projective navigation system can be a powerful tool for pre-operative
surgical planning, intraoperative surgical guidance, and postoperative assessment of surgical outcome. We have
integrated the optoelectronic elements into a compact and miniaturized system in preparation for further clinical
Biomedical optical devices are widely used for clinical detection of various tissue anomalies. However, optical measurements have limited accuracy and traceability, partially owing to the lack of effective calibration methods that simulate the actual tissue conditions. To facilitate standardized calibration and performance evaluation of medical optical devices, we develop a three-dimensional fuse deposition modeling (FDM) technique for freeform fabrication of tissue-simulating phantoms. The FDM system uses transparent gel wax as the base material, titanium dioxide (TiO2) powder as the scattering ingredient, and graphite powder as the absorption ingredient. The ingredients are preheated, mixed, and deposited at the designated ratios layer-by-layer to simulate tissue structural and optical heterogeneities. By printing the sections of human brain model based on magnetic resonance images, we demonstrate the capability for simulating tissue structural heterogeneities. By measuring optical properties of multilayered phantoms and comparing with numerical simulation, we demonstrate the feasibility for simulating tissue optical properties. By creating a rat head phantom with embedded vasculature, we demonstrate the potential for mimicking physiologic processes of a living system.
We describe a portable fluorescence goggle navigation system for cancer margin assessment during oncologic surgeries.
The system consists of a computer, a head mount display (HMD) device, a near infrared (NIR) CCD camera, a miniature
CMOS camera, and a 780 nm laser diode excitation light source. The fluorescence and the background images of the
surgical scene are acquired by the CCD camera and the CMOS camera respectively, co-registered, and displayed on the
HMD device in real-time. The spatial resolution and the co-registration deviation of the goggle navigation system are
evaluated quantitatively. The technical feasibility of the proposed goggle system is tested in an ex vivo tumor model.
Our experiments demonstrate the feasibility of using a goggle navigation system for intraoperative margin detection and