We developed a heat-sensitive microbubble (HSM) agent for intraoperative assessment of
thermal ablation margins in cancer ablation therapies. The HSM agent, comprising a core
of liquid perfluorocarbon (PFC) compound and a shell of biodegradable poly lactic-coglycolic
acid (PLGA), was fabricated using an emulsion evaporation method. In our
previous study, significant increase of ultrasound contrast was observed after heat
activation of HSMs. In this study, intraoperative ultrasonic assessment of thermal
ablation margins by HSMs was demonstrated in vivo in a pig model. HSMs were
delivered to the pig liver by portal vein injection. Liver ablation was done using a RF
ablation probe. Intraoperative ultrasound imaging with HSMs clearly delineated the
ablation margin. Fluorescence images of liver tissue samples confirmed the existence and
activation of HSMs. This result demonstrated that the HSM agent can be potentially
utilized as a multimodal contrast agent for intraoperative ultrasonic and fluorescence
assessment of thermal ablation margins in cancer ablation therapies.
We synthesize drug-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for image-guided combinatory epigenetic therapy in MCF-10A human mammary epithelial cells. LY294002 and Nile Red are encapsulated in microspheres for sustained drug release and fluorescence microscopic imaging. Drug-loaded microspheres target MCF-10A cells through a three-step binding process involving biotinylated antibody, streptavidin, and biotinylated microspheres. LY294002 loaded microspheres and 5-Aza-2-deoxycytidine are applied to MCF-10A cells for combinatory PI3K/AKT inhibition and deoxyribonucleic acid (DNA) demethylation. Our study implies the technical potential of disease targeting and image-guided combinatory epigenetic therapy using drug-loaded multifunctional biodegradable PLGA microspheres.
We synthesize multifunctional microbubbles (MBs) for targeted delivery of antivascular endothelial growth factor (antiVEGF) therapy with multimodal imaging guidance. Poly-lactic-co-glycolic acid (PLGA) MBs encapsulating Texas Red dye are fabricated by a modified double-emulsion process. Simultaneous ultrasound and fluorescence imaging are achieved using Texas Red encapsulated MBs. The MBs are conjugated with Avastin, an antiVEGF antibody for treating neovascular age-related macular degeneration (AMD). The conjugation efficiency is characterized by enzyme-linked immunosorbent assay (ELISA). The efficiency for targeted binding of Avastin-conjugated MBs is characterized by microscopic imaging. Our work demonstrates the technical potential of using multifunctional MBs for targeted delivery of antiVEGF therapy in the treatment of exudative AMD.
Bevacizumab (Avastin) has been used as one of the anti-VEGF therapies to manage neovascular age-related macular degeneration (AMD). The drug delivery system for bevacizumab needs to be improved in order to decrease the frequency of injection and reduce the adverse effects. In our study, bevacizumab was conjugated with poly
(lactic-co-glycolic acid) (PLGA) microbubbles by activating carboxyl functional groups. The averaged size of microbubbles was estimated 1.055±0.258μm, allowing for ultrasound guided drug delivery. The binding efficiency between bevacizumab and microbubbles was evaluated in an enzyme-linked immunosorbent assay plate. The test results demonstrated the potential of using PLGA microbubbles to deliver bevacizumab with imaging guidance.
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
cancers.
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
imaging.
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.
Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are
important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing
cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative
information that supports critical decision-making in the operating room.
Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a
modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72
antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were
encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were
explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies.
Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms,
LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated
using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging
tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model.
Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative
detection of tumor boundaries and therapeutic margins.
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.
We developed a novel dual-modal contrast agent for the structural and functional imaging of cancer. The contrast agent was fabricated by encapsulating indocyanine green (ICG) in poly(lactic-co-glycolic acid) (PLGA) microbubbles using a modified double-emulsion method. More stabilized absorption and fluorescence emission characteristics were observed for aqueous and plasma suspensions of ICG-encapsulated microbubbles. The technical feasibility of concurrent structural and functional imaging was demonstrated through a series of benchtop tests in which the aqueous suspension of ICG-encapsulated microbubbles was injected into a transparent tube embedded in an Intralipid phantom at different flow rates and concentrations. Concurrent fluorescence imaging and B-mode ultrasound imaging successfully captured the changes of microbubble flow rate and concentration with high linearity and accuracy. One potential application of the proposed ICG-encapsulated PLGA microbubbles is for the identification and characterization of peritumoral neovasculature for enhanced coregistration between tumor structural and functional boundaries in ultrasound-guided near-infrared diffuse optical tomography.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.