Download Research Title: Gold Nanoparticles for Multiple Selective

Research Title: Gold Nanoparticles for Multiple Selective Photothermal Therapy and
Photoacoustic Imaging
PI: Professor Pai-Chi Li
Co-PI: Professor Churng-Ren Wang, National Chung-Cheng University, Professor
Dar-Bin Shieh, National Cheng-Kung University Hospital
Abstract: The long-term goal of this project is to utilize unique characteristics of gold
nanopaticles and to develop advanced photoacoustic imaging and photothermal therapy
technologies. To meet this long-term goal, the research tasks in the proposed three-year
project period will focus on (1). development of advanced photoacoustic micro-imaging
technologies for quantitative analysis, measurements of hemodynamic functions, and
simultaneous detection of multiple selective targeting; (2). evaluation of selective
photothermal therapy technologies, and (3). biocompatibility tests of conjugated gold
nanoparticles. The program project is primarily motivated by the unique properties of
gold nanorods. These properties include the shape dependence of the photoacoustic
response and the shape transformation under laser irradiation. With these properties, the
above mentioned advanced biomedical technologies can be developed. With the in vitro
verification, in vivo animal imaging and the biocompatibility evaluation of the
nanoparticles, the long-term goal can thus be pursued. The program project consists of
three component projects, covering all aspects of the research problem from physics and
imaging, nano materials and chemistry, to biology and medicine. A core unit will also be
established to provide bioconjugated gold nanoparticles to all component projects. To this
end, specific aims of this project include:
- Development of backward mode imaging methods for reconstruction of optical
absorption coefficient.
- Construction of a photoacoustic micro-imaging system with high frame rate and
high spatial resolution.
- Evaluation of simultaneous detection of multiple selective targeting (for
molecular imaging).
- Investigation of blood flow and perfusion measurement techniques (for
functional imaging).
- Modeling, simulations and optimization of optical, thermal and acoustic
properties of nanoparticles.
- Testing of the in vitro cytotoxicity, genotoxicity, hemocompatibility, acute and
subacute systemic toxicity of the nanorods with different shapes and surface
modifications.
Finally, this project will use oral cancer as a target model for integration of research
efforts and a vehicle for technology development. With the success of this project, the full
potential of gold nanoparticles in biomedical sciences can then be fully realized.
Research Title: Advanced wireless medical imaging microsystem: core technology
development of devices, systems and clinical diagnosis
PI: Professor Pai-Chi Li
Co-PI: Professor Shen-Iuan Liu, Professor Tsung-Hsien Lin, Professor An-Yeu We,
Professor Chih-Wen Liu, National Taiwan University. Dr. Chao-Min Wong, National
Taiwan University Hospital and Dr. Chi-Shih Lien, Wan-Fang Hospital.
Abstract: The long term goal of this integrated project is to develop next generation
biomedical electronics technologies. By combining micro array sensors, wireless
transmission, low power digital signal processing engine, magnetic remote position
control, medical image analysis and tissue characterization, this project will fully
integrate electronics and communication technologies with biomedical measurements and
diagnosis, and achieve the ultimate goal of this special NSC project. To achieve the above
long term goal, the project will aim for developing system and device technologies for
wireless capsule ultrasound endoscope as the short term goal, and conduct system
integration (including integration with the existing optical capsule endoscope
technologies) and extend the applications to clinical diagnosis and image guided therapy
as the mid term goal. The project consists of the following research items:
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Research and production of ultrasound micro annular arrays, and innovative
applications to capsule imaging systems
Multi-plane medical image formation, analysis and tissue characterization
Establishment of optical endoscope and ultrasound endoscope multi-modality
medical image database
Low power wireless transceiver design for biomedical image applications
(requiring a much higher data rate compared to current biomedical wireless
transmission applications)
High efficiency wireless power transmission circuits
Low power digital signal processing engine architecture
Remote magnetic position control technologies
Research title: Ultrasound Assisted Liposomal Cancer TherapyPI: Professor Pai-Chi Li
Co-PI: Dr. Leuwei Lo and Dr. Chiung-Tong Chen, National Health Research
Institutes
Abstract: The prevalence of cancer disease is a major health problem worldwide. Cancer
has been the leading cause of death over the past two decades in Taiwan. Other than the
lung, colorectal and breast cancer, these cancer diseases in Taiwan are also prevalent in
other Asian countries and are, however, relatively uncommon in the United States and
Europe. This project focuses on the development of a system involving targeting delivery
for liposomal air-bubbles and ultrasound-assisted release of the drug carried in liposome
particles. In fact, it is an integration of micro-imaging, nano-medicine, molecular and
cellular probes, targeting and drug release. The main research items are:
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Develop new types of liposomal bubbles with improved cavitational
characteristics
Integrate both diagnosis and therapy into a single system
Combine cavitation assisted therapy with drug delivery
Validate a new cancer evaluation technique that includes the oxygen, glucose,
morphology and vascularity
Xenograft and in situ models of cancer cells
Focus on the local cancer diseases
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Research title: Ultrasonic breast imaging based on new imaging parameters
PI: Professor Pai-Chi Li
Abstract: Breast cancer detection has become increasingly important in recent years due
to its high occurrence and death rate. Ultrasonic imaging has become an indispensable
diagnostic tool and a good complement to other clinical tools such as X-ray
mammography. In addition, ultrasound-based computer aided diagnosis has also been
extensively studied with impressive research results. However, performance of
conventional breast ultrasonic imaging, whose image parameter and contrast mechanism
are based on the acoustic scattering properties, is still limited and it suffers from image
quality degradation. The primary source of the limitations is the tissue inhomogeneities,
which result in focusing errors and degrade its clinical performance. Therefore, the
primary goal of this three-year research project is to develop next-generation imaging
technologies which can be implemented in existing array imaging systems. Specifically,
the new imaging technologies are based on the sound velocity distribution in tissue as the
image parameter. With the success of this project, the breast ultrasound image quality and
its concomitant clinical values can be drastically improved. In addition, the project will
also explore the possibility of combining the proposed imaging methods with other
advanced front-end imaging techniques, such as compounding and elasticity imaging. To
this end, the proposed research project will address the following technical issues:
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Study, modeling and simulation of acoustic wave propagation in breast tissue.
Tomographic reconstruction of sound velocity distribution using data acquired
from existing linear transducer arrays.
Development of sound velocity correction methods for conventional B-mode
ultrasound, based on the reconstructed sound velocity distribution using the
approach proposed in this project.
Experimental setups, including both conventional ultrasound computed
tomography and data acquisition using existing linear array imaging systems.
Combination of the proposed methods with other advanced imaging techniques,
such as compounding and elasticity imaging.
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Research title: Ultrasonic Micro-Imaging Systems for Biotechnology Research
PI: Professor Pai-Chi Li
Industry Partner: Cold Spring Biotech Corp.
Abstract: Cancer research, drug development and developmental biology are three of the
most important research topics in the areas of biotechnologies and small animal models
have been widely used in these areas. Hence, the use of advanced and non-invasive
imaging technologies in improving the research quality and reducing the development
time and cost has become an increasingly important issue. In particular, mouse animal
models have been widely used because of the small size and ease in maintaining the
animal facilities. It has been reported that there are several millions of mice sacrificed for
biotechnology research each year, with a growth rate over 10%. Because the size and
weight of a small animal is only 1/1000 of those of an adult, small animal imaging
requires excellent spatial resolution and sensitivity. This is also the main motivation of a
three-year project funded by NSC in 2002. The current proposal is a continuation of the
previous research project, with a goal to realize the advanced imaging methods and to
assist research in embryo imaging, cardiac imaging and tumor imaging. To ensure
success, this project will focus on system integration and optimization of transducer
production procedures. Additionally, success of this project is also critical for subsequent
technology transfer and to the industry of biomedical electronics. To this end, the main
tasks of this proposed research project include:
- Development of systems and algorithms for real-time imaging.
- Optimization of transducer production procedures for micro-imaging.
- Applications of molecular probes in ultrasonic micro-imaging.
- Design of image registration method for ultrasound/PET imaging.
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