A dual-mode imaging technique has been developed for intraoperative imaging of bile ducts and real-time identification
of iatrogenic injuries in cholecystectomy. The technique is based on ultrasound (US) and fluorescence (FL) imaging of a dual-mode microbubble (MB) agent comprising a poly (lactic-co-glycolic acid) (PLGA) shell and a core of Indocyanine
Green. During cholecystectomy, a clinical US probe is used to localize the bile duct structure after bolus injection of dual-mode MBs. As the surrounding adipose tissue is removed and the Calot’s triangle is exposed, FL imaging is used to
identify the MB distribution and to determine the potential bile duct injury. The contrast-enhanced bile duct imaging
technique has been demonstrated in both a surgical simulation model and an ex vivo porcine tissue model under two surgical scenarios. The first scenario simulates the correct procedure where the cystic duct is clipped. The second
scenario simulates the incorrect procedure where the common bile duct is clipped, leading to consequent bile duct injury. Benchtop experiments in both the phantom and the ex vivo models show that the dual-mode imaging technique is able to
identify the potential bile duct injury during cholecystectomy. A phantom system has also been established for future
device calibration and surgical training in image-guided cholecystectomy. Further in vivo animal validation tests are necessary before the technique can be implemented in a clinical setting.
Background: Clinical ultrasound (US) uses ultrasonic scattering contrast to characterize subcutaneous anatomic
structures. Photoacoustic (PA) imaging detects the functional properties of thick biological tissue with high optical
contrast. In the case of image-guided cancer ablation therapy, simultaneous US and PA imaging can be useful for
intraoperative assessment of tumor boundaries and ablation margins. In this regard, accurate co-registration between
imaging modalities and high sensitivity to cancer cells are important.
Methods: We synthesized poly-lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs)
encapsulating India ink or indocyanine green (ICG). Multiple tumor simulators were fabricated by entrapping ink MBs
or NBs at various concentrations in gelatin phantoms for simultaneous US and PA imaging. MBs and NBs were also
conjugated with CC49 antibody to target TAG-72, a human glycoprotein complex expressed in many epithelial-derived
Results: Accurate co-registration and intensity correlation were observed in US and PA images of MB and NB tumor
simulators. MBs and NBs conjugating with CC49 effectively bound with over-expressed TAG-72 in LS174T colon
cancer cell cultures. ICG was also encapsulated in MBs and NBs for the potential to integrate US, PA, and fluorescence
Conclusions: Multifunctional MBs and NBs can be potentially used as a general contrast agent for multimodal
intraoperative imaging of tumor boundaries and therapeutic margins.
Many advantages of biomedical optical imaging modalities include low cost, portability, no radiation hazard, molecular
sensitivity, and real-time non-invasive measurements of multiple tissue parameters. However, clinical acceptance of
optical imaging is hampered by the lack of calibration standards and validation techniques. In this context, developing
phantoms that simulate tissue structural, functional, and molecular properties is important for reliable performance and
successful translation of biomedical optical imaging techniques to clinical applications.
Over the years, we have developed various tissue simulating phantoms to validate imaging algorithms, to optimize
instrument performance, to test contrast agents, and to calibrate acquisition systems. We also developed phantoms with
multimodal contrasts for co-registration between different imaging modalities. In order to study tissue dynamic changes
during medical intervention, we develop gel wax phantoms to simulate tissue optical and mechanical dynamics in
response to compression load. We also dispersed heat sensitive microbubbles in agar agar gel phantoms to simulate heatinduced
tissue coagulative necrosis in a cancer ablation procedure. The phantom systems developed in our lab have the
potential to provide standardized traceable tools for multimodal imaging and image-guided intervention.
Accurate assessment of wound oxygenation and perfusion is important for evaluating wound healing/regression and
guiding following therapeutic processes. However, many existing techniques and clinical practices are subjective and
qualitative due to background bias, tissue heterogeneity, and inter-patient variation. To overcome these limitations, we
developed a dual-modal imaging system for in vivo, non-invasive, real-time quantitative assessment of wound tissue
oxygenation and perfusion. The imaging system integrated a broadband light source, a high-resolution CCD camera, a
highly sensitive thermal camera, and a liquid crystal tunable filter. A user-friendly interface was developed to control all
the components systematically. Advanced algorithms were explored for reliable reconstruction of tissue oxygenation and appropriate co-registration between thermal images and multispectral images. Dual-mode oxygenation and perfusion imaging was demonstrated on both benchtop models and human subjects, and compared with measurements using other methods, such as Laser Doppler and tissue oximeter. The test results suggested that the dual-modal imaging system has the potential for non-contact real-time imaging of wound tissue oxygenation and perfusion.
We develop a novel dual-modal contrast agent-encapsulated-ink poly(lactic-co-glycolic acid) (PLGA) microbubbles and nanobubbles-for photoacoustic and ultrasound imaging. Soft gelatin phantoms with embedded tumor simulators of encapsulated-ink PLGA microbubbles and nanobubbles in various concentrations are clearly shown in both photoacoustic and ultrasound images. In addition, using photoacoustic imaging, we successfully image the samples positioned below 1.8-cm-thick chicken breast tissues. Potentially, simultaneous photoacoustic and ultrasound imaging enhanced by encapsulated-dye PLGA microbubbles or nanobubbles can be a valuable tool for intraoperative assessment of tumor boundaries and therapeutic margins.