Churng-Ren Wang

National Chung Cheng University

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Pai‐Chi Li

National Taiwan University

Ai‐Ho Liao

National Defense Medical Center

Yu-Hsin Wang

Chang Gung University

Chao-Kang Liao

Imec the Netherlands

Chen‐Wei Wei

Guangxi University of Science and Technology

Chih‐I Wu

National Taiwan University

Ya‐Na Wu

National Cheng Kung University

Yu‐Ting Weng

National Taiwan University

Sheng‐Wen Huang

Guizhou Provincial People's Hospital

Carolina Poe

National Chung Cheng University

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National Taiwan University

National Chung Cheng University

National Cheng Kung University

National Science and Technology Council

National Tsing Hua University

National Taipei University of Technology

National Yang Ming Chiao Tung University

National Cheng Kung University Hospital

National Taiwan University of Science and Technology

National Health Research Institutes

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Photoacoustic Flow Measurements with Gold Nanoparticles

CRC Press eBooks (2017)

Pai‐Chi Li Chen‐Wei Wei Sheng‐Wen Huang Chao-Kang Liao Churng-Ren Wang

The combination of high optical contrast and low acoustic scattering has made photoacoustics (PA) a promising tool in several biomedical applications, including blood oxygenation monitoring and breast tumor detection. This chapter describes PA methods for quantitative blood flow estimation. It also describes the shape-dependent absorption spectrum and photo-induced shape transition properties of gold nanoparticles to facilitate flow measurements. In particular, gold nanoparticles are used as the contrast agent for signal enhancement and for time-intensity curve (TIC) measurements. For the dual-energy method, only the TIC in the replenishment step is used to estimate the flow velocity. The chapter presents the mathematical models and measurement results for wash-out TICs and wash-in TICs. It discusses potential clinical applications and performance issues. For in vivo applications, the TIC can also be measured using a sequence of two-dimensional (2D) images. As a demonstration, TIC measurements were conducted with a perfusion phantom, which was constructed from an optically and acoustically transparent material.

10.1201/9781420059922-41

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in vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods

Nature Precedings (2008)

Pai‐Chi Li Dar‐Bin Shieh Churng-Ren Wang Chen‐Wei Wei Chao-Kang Liao

Abstract The use of gold nanorods for photoacoustic molecular imaging in vivo with simultaneous multiple selective targeting is reported. The extravasation of multiple molecular probes is demonstrated, and used to probe molecular information of cancer cells. This technique allows molecular profiles representing tumor characteristics to be obtained and a heterogeneous population of cancer cells in a lesion to be determined. The results also show that the image contrast can be enhanced by using a mixture of different molecular probes. In this study, HER2, EGFR, and CXCR4 were chosen as the primary target molecules for examining two types of cancer cells, OECM1 and Cal27. OECM1 cells overexpressed HER2 but exhibited a low expression of EGFR, while Cal27 cells showed the opposite expression profile. Single and double targeting resulted in signal enhancements of up to 3 dB and up to 5 dB, respectively, and hence has potential in improving cancer diagnoses.

Molecular Imaging

Nanorod

Molecular probe

10.1038/npre.2008.1687.1

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Thermotherapy with a photoacoustic/ultrasound dual-modality agent

Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE (2011)

Yu-Hsin Wang Ai‐Ho Liao Jui-Hao Chen Yi‐Hsien Lee Churng-Ren Wang

A microbubble-based imaging/therapeutic agent is introduced. Specifically, gold nanoparticles (AuNRs) are encapsulated in microbubbles (MBs) for both ultrasound (US) imaging and laser-induced thermotherapy (LIT). In addition, this agent, AuNR-MB, takes albumin microbubble as a carrier and includes the AuNRs that maintain the original absorption peak at around 760nm. AuNR-MBs in different sizes are synthesized. Imaging is first performed to evaluate its feasibility. The enhanced PA and US signals in polyacrylamide gel for in vitro study are measured. The PA spectroscopy is then performed and the results generally agree with the measured optical absorption although its peak is slightly broadened and shifted possibly due to mixing. In phantoms, the contrast is 1.531, 2.447, 2.085, 1.994, 0.768, and 0.573 at wavelength of 720, 760, 800, 860, 900, and 940 nm respectively. Finally, the application of the new agent to LIT is presented. A continuous wave laser at 800 nm is used to heat the samples with the power at 1W. The photoacoustic (PA) intensity in the region of interest (ROI) is increased by an average of 5.2dB. The increased signal level implies that the temperature in the ROI can be increased to 44.3°C in aqueous filled setup. Furthermore, the dual-modality agent has the potential to be used in HIFU therapy, drug delivery and loading of DNA for gene transfer.

10.1117/12.875667

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An imaging/therapeutic molecular probe for ultrasound and photoacoustic dual modality system

IEEE International Ultrasonics Symposium (2010)

Ai‐Ho Liao Yu-Hsin Wang Yu‐Ting Weng Churng-Ren Wang Pai‐Chi Li

Gold nanorods (AuNRs) have been used as contrast enhancement agents for photoacoustic (PA) imaging as well as effective photothermal therapy agents. In the literature, pulsed ultrasound exposures have shown to enhance delivery of fluorescently labeled polystyrene nanoparticles. Microbubbles (MBs) can also substantially enhance the ablation effects. In this study, we develop a US/PA imaging/therapeutic multimodality molecular probe - encapsulated gold nanorods albumin microbubbles (AuMBs) for US/PA imaging. The AuNR solution containing 0.4-M Cysteamine dihydrochloride (5 ml) and 16 mM HNO3 (10 ml) is aged for 30 min. Next, the solution is centrifuged at 5500 rpm for 15 min to remove excess cysteamine. Human serum albumin is added into the AuNR solution and then aged for 24 hour at 4°C. AuNR targeted MBs were generated by sonicating 4 mL of solution containing 1.2% AuNR-HSA, 0.04% avidin, and C ₃ F ₈ gas in phosphate-buffered saline. The AuMBs concentration was 2.41×10 ⁹ /ml, and their mean diameter was 1319 nm. Phantom experiments were performed to characterize the AuMBs using Polyacrylic Acid gels with a chamber to load the samples. The property of the AuMBs for US/PA dual imaging system was estimated, and modified as a molecular probe. The optical characteristics of the AuMBs were presented. In addition, the potential of the AuMBs in the enhancement of the AuNR based hyperthermia was investigated.

Molecular Imaging

10.1109/ultsym.2010.5935815

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Enhanced delivery of gold nanoparticles by acoustic cavitation for photoacoustic imaging and photothermal therapy

Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE (2013)

Yu-Hsin Wang Ai‐Ho Liao Jiayu Lin Cheng-Ru Lee Chih‐I Wu

Gold-nanorods incorporated with microbubbles (AuMBs) were introduced as a photoacoustic/ultrasound dual- modality contrast agent in our previous study. The application can be extended to theragnosis purpose. With the unique physical characteristics of AuMBs, we propose an enhanced delivery method for the encapsulated particles. For example, laser thermotherapy mediated by plasmonic nanoparticles can be made more effective by using microbubbles as a targeted carrier and acoustic cavitation for enhanced sonoporation. The hypothesis was experimentally tested. Firts, these AuMBs first act as molecular probes with binding to specific ligands. The improved targeting efficacy was macroscopically observed by an ultrasound system. The extended retention of targeted AuMB was observed and recorded for 30 minutes in a CT-26 tumor bearing mouse. Secondly, cavitation induced by time-varying acoustic field was also applied to disrupt the microbubbles and cause increased transient cellular permeability (a.k.a., sonoporation). Multimodal optical microscope based on a Cr:forsterite laser was used to directly observe these effects. The microscope can acquired third-harmonic generation (THG) and two-photon fluorescent (2PF) signals produced by the AuMBs. In vitro examination shows approximately a 60% improvement in terms of fluorescence signals from the cellular uptake of gold nanoparticles after sonoporation treatment. Therefore, we conclude that the controlled release is feasible and can further improve the therapeutic effects of the nanoparticles.

Sonoporation

10.1117/12.2005870

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Citations (3)