System development and clinical applications of the handheld PA/US dual mode imaging system

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Zhao, Lingyi
Li, Changhui
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As an emerging technology, photoacoustic (PA) imaging (PAI) has gained lots of progresses in the past two decades. By combing optical contrast with ultrasound detection, PAI can maintain high spatial resolution in deeper regions. Furthermore, with the aid of multispectral imaging, PAI can reveal functional information such as oxygenation saturation (SO2), which is closely related to tumor malignancy. With the above advantages, nowadays PAI has gained lots of progresses in clinically translatable research. These research shows that PAI has the potential to complement existing imaging techniques such as ultrasound (US) imaging for cancer detection, disease evaluation and prognosis monitoring. This thesis mainly discusses the clinical application of PAI, including system design and clinical research. Particularly, it presents several studies including the development of PA/US imaging system and the clinical evaluation of PA/US imaging in diagnosis of superficial cancer. The main research results and the major novelties of this thesis include: 1) The collaborative development of the PA/US imaging system for clinical studies, where the author was mainly responsible for the design of optical path and the trigger method between the laser and the US system. 2) The design of optical fluence compensation strategy based on clinical US structural imaging. This strategy first identifies the tissue type based on US structural imaging, and then utilizes the known optical absorption and scattering parameters to simulate optical fluence map in the imaging region. The simulated optical fluence map can then be used for correction of original PA images. The effectiveness of this strategy has been verified based on clinical PAI data. The proposed method can improve the accuracy of quantification PAI and restore PA signals in deeper regions. 3) The collaborative study of PA/US imaging on thyroid nodules with the self-developed 2D PA/US handheld imaging system. By comparing PAI results with color Doppler flow imaging (CDFI) results from 10 thyroid nodules, we found that PAI can reveal more abundant vessels than CDFI, and can thus provide valuable information in diagnosis of thyroid cancer. 4) The design of the method for quantification analysis of 3D PA/US imaging on breast cancer. Specifically, this method first calculates the ellipse enclosing the tumor region with the minimum volume and then automatically segments the tumor regions and tumor surrounding regions. Next, the volumetric mean SO2 of tumor regions and tumor surrounding regions were calculated for quantification analysis. Our results demonstrate that quantification analysis of 3D functional PA/US imaging on breast cancers has the potential to improve the specificity in diagnosis of breast cancer. In Chapter 1, the mechanism of PAI and its recent clinical translational progresses are first reviewed. Next, in Chapter 2, the development of a clinical PA/US imaging system based on handheld US imaging is presented. The imaging ability of the newly developed system was verified with the phantom study as well as the in vivo study. After then, in Chapter 3, the optical fluence compensation method for handheld PA/US imaging based on tissue structural information provided in US imaging is introduced. The clinical result demonstrates that important tissue structures such as vessels in deeper tissue can be restored after fluence compensation based on the proposed method. Chapter 4 and Chapter 5 introduce the clinical studies based on the self-developed PA/US imaging systems, including 2D PA/US imaging of thyroid nodules, 3D PA/US imaging of breast cancer, and quantification analysis of the imaging results. The quantification analysis demonstrates that 3D functional PA/US imaging has the potential to improve the diagnosis specificity of breast cancer. In Chapter 6, the author presented the research conducted in Georgia Institute of Technology. In this chapter, the laser induced surface acoustic waves (SAWs) and acoustic radiation force (ARF) induced SAWs were compared. The results demonstrate that laser-induced SAW imaging is able to perform stiffness evaluation and has the potential to provide higher spatial resolution. In Chapter 7, the author summarized the major novelties in this thesis and discussed research directions in the future work.
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