Photoacoustic Imaging Alogrithms And Experimental Study Of Breast Cancer

Breast cancer is the first major killer to threaten the health of women world widely in the 21 st century,especially in China,which became a major public problem endangering human health.As a noninvasive biomedical imaging modality that has flourished in recent years,photoacoustic(PA)imaging is a light in and sound out technology with high acoustic resolution up to nanometers.It can create multicontrast images of living biological structures ranging from organelles to organs,providing anatomical,functional,metabolic,molecular,and genetic contrasts,which could be potentially applied in breast cancer imaging.In its early stage,the hemoglobin in the disorganized vessels could provide as the PA endogenous contrast agent to monitor the angiogenesis;while in the metastatic stage,a series of cancer factor may serve as the target for exogenous contrast agents.Therefore,in virtue of the tumor targeted nanoprobe,it is of great significance to study the PA imaging to monitor the cancer in situ and detect the tumor in the metastatic routine,which could provide a guidance for early detection,early diagnosis and early treatment of breast cancer.In view of the urgent need for PA imaging of breast cancer,this work studies the feasibility of signal detection,laser irradiation pattern,light and sound coupling,and the corresponding reconstruction methods in photoacoustic tomography(PAT).The hemi-spherical structure of breast,signal penetration depth,imaging speed and spatial resolution should be deliberately considered in both imaging the breast cancer in situ and metastic routines,such as lymph node,peripheral blood vessels,lung and liver.For imaging these regions with full view observation and accelerated data acquisition,here the detector performance and light illumination was comprehensive evaluated.In this study,a virtual point detector based circular scanning PAT and the optimized backprojection method were given first on the condition of coplanar light illumination and ultrasonic detection,where the signal to noise ratio increased 16 d B with 2 folds resolution enhancement compared with the flat transducer.Further,according to the spatial compounding principle,a feasible synthetic aperture PAT system based on the compressed sensing method was proposed to address the limited view problem while preserving target information with 4 times fewer of measurements.In order to obtain accurate information,the quantitative photoacoustic tomography(q PAT)was introduced to estimate the spatially varying optical absorption parameters from heterogonous acoustic signals.The breast and metastic regions consist of skin,muscle,fat,mammary duct,as well as the blood vessels and glands distributed under the skin.The optical and acoustic scattering,reflection,refraction,attenuation,optical absorption and acoustic velocity are different within various tissue layers and depths,which could provide a challenge in current quantitative imaging.Here I focused on the compensation of the optical fluence and variable sound speed,the accuracy of measured vessel size after the optical flunce compensation could increase ~10%,while the tumor detection increment could improve to 37.56% with the variable speed compensation.Through the quantitative method,the inner structure,target size and depth information could be accurately detected,which could promote the PA imaging further towards theoretical and clinical transformation.On the basis of PA imaging methods and systems,an experimental study of PA imaging of breast cancer was conducted.In the early stage,the hemoglobin in the angogensis could be served as a label-free endogenous contrast agent to generate significant PA signal to visualize the malignant tumor growth with photoacoustic microscopy(PAM).Subsequently,the circulating tumor cells could enter the lymph system and blood circulation,the metastatic tumor could be specific targeted in cellular level with high sensitivity nanoprobes,such as quaterrylene denrimers(QR)for human breast cancer cells and human serum albumin indocyanine green nanoparticles(HSA-ICG NPs)for mouse breast cancer cells.Then the in vitro cell study could be conducted with PAM,and the metastatic routines could be visualized in vivo mouse study with PAT.Compared with the background tissue,the probe targeted tumor shows high signal intensity,demonstrating its imaging ability of early primary lesions and micrometastasis pathways of breast cancer.Regarding the clinical imaging need and pathophysiology of breast cancer,a series of methods,such as virtual point detector,coplanar light and acoustic detection,synthetic aperture,sparse sampling,compressed sensing,quantitative imaging,and tumor targeted nanoparticles were studied to photoacoustically visualize the cancer.The huge dataset from the full view observation,limited-view problem,and the inaccurate quantitative analysis were addressed,especially the backprojection method optimization and the design of PA compressive measurement matrix.The tumor targeted probes were characterized and imaged on animal models,which could simulate the human mechanism.Orthotopic breast cancer was studied at the cellular level and metastic routines were continuously monitored in vivo mouse study.Metastasis-guided photoacoustic/ultrasound(PA/US)imaging was performed,and precise morphological localization and edge detection were imaged on lymph nodes and lung area.Meanwhile,with the complementary advantages of PA,US,and fluorescence(FL)multimodality imaging,the structure and function information of potential tumors,benign lesions,and normal breast cancers were evaluated,which has potential clinical implications for the diagnosis of breast cancer.