Applications of Gold Nanoparticles in Photoacoustic Biomedical Imaging
Date Issued
2009
Date
2009
Author(s)
Wei, Chen-Wei
Abstract
Photoacoustic imaging is a new imaging technique that has been used to image the optical properties of biological tissues. However, the applications of photoacoustic imaging in most researches have been limited to morphological observations. Also, high optical scattering of biological tissues and depth dependent decay of incident optical energy degrade the detection sensitivity. In this thesis, the use of gold nanoparticles as photoacoustic contrast agents helps to increase the sensitivity of photoacoustic imaging and to extend the applications to functional and molecular imaging, including cardiac functional assessment and cancer diagnosis. In the first part of the thesis, quantitative blood flow measurements based on the time-intensity method were tested. Gold nanoparticles were used as a photoacoustic contrast agent. In wash-in methods, the photo-induced rod-to-sphere shape transformation of gold nanorods was utilized. Results show that the correlation coefficients between the measured velocities and the true values are close to unity. For molecular imaging, photoacoustic imaging was utilized to probe information from oncogene surface molecules of oral cancer cell, OECM1 and Cal27, with the aid of bioconjugated gold nanorods. In vitro cell culture and in vivo small animal results show that both cancer cells with antibody conjugated nanorods of specific targeting exhibit a higher photoacoustic response than control groups with plain nanorods. Also, angiogenesis targeting was achieved with peptide conjugated gold nanorods. Images of OECM1 tumor with mixed nanoprobes injection also reveal enhanced photoacoustic intensity at different wavelengths than those with mixed plain gold nanorods injection, thus demonstrating simultaneous multiple targeting is feasible and can be used to obtain variable molecular signatures by simply switching laser wavelength. Also, photoacoustic pressure amplitude, which is linearly correlated with temperature, can be applied for real-time monitoring of the temperature non-invasively during photothermal therapy. Quantitative thermal imaging showed that the temperature can reach the hyperthermia level for effective cancer treatment. The results of pathological analysis of the tumor confirm the necrosis of the tumor cells without damaging surrounding normal cells. In the last part of the thesis, a subband imaging method to further enhance the image contrast was developed. The method was based on that high-absorption media generate acoustic waves with higher frequency components, and hence the imaging contrast can be enhanced by appropriate selection of the spectral subbands. The experimental results revealed that the contrast between two absorbers with eight times difference in optical absorption can be effectively increased by choosing a higher subband. These methods help to recognize the region of interest with gold nanoparticles particularly for in vivo studies. In summary, the thesis has realized photoacoustic functional and molecular imaging including quantitative flow/perfusion estimation and multiple targeting on tumor with the aid of gold nanoparticles. Future works will focus on in vivo flow estimation on tumor angiogenesis and improvement of detection sensitivity.
Subjects
photoacoustic imaging
gold nanoparticle
blood flow estimation
time-intensity curve
molecular imaging
multiple targeting
targeted thermal therapy
subband imaging
SDGs
Type
thesis
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