Photoacoustic And Fluorescence Molecular Imaging Fusion: Methods And Applications

Photoacoustic and optical imaging fusion can provide more comprehensive and accurate anatomical,physiological and pathological information for basic biomedical research.Based on the theory of photoacoustic and optical imaging,a photoacoustic and optical imaging fusion system is developed,and the experiments are carried out to analyze the characters of photoacoustic and optical molecular imaging.Finally,we use multi-modality imaging method in the early detection of hepatocellular carcinoma.The main achieves of this thesis are as follows:A method of photoacoustic and optical mutual enhancement imaging fusion is proposed to obtain more accurate information about the structure and function of living organisms.For now,the common methods of multi-modality image fusion are simply to register the multimodal image data.PET/CT is a typical representative of this method.However,this fusion method just combines the information of the imaging modalities,does not fully mining the information complementarity of different imaging modalities,and also can not improve the imaging quality of each imaging modality.However,the photoacoustic and optical imaging fusion problems have special background,photoacoustic imaging and optical imaging are respectively based on "photoacoustic effect" and the "fluorescence effect",which have a physical link.So we can combine the photoacoustic imaging and optical imaging with the level of imaging models and algorithms to enhance the imaging quality.In this thesis,we suggested a photoacoustic and optical molecular imaging fusion method to combine with the high resolution and resolution of photoacoustic imaging and the high sensitivity and specificity of optical molecular imaging,which can offer more accurate and comprehensive information of the living animals for basic and pre-clinical researches.A photoacoustic and optical fusion imaging system was developed.The fusion system is the foundation of the fusion algorithm and application researches.The system consists of fluorescence molecular tomography device and photoacoustic tomography device.The two devices share the same small animal bearing module,which can carry out high precise rotation and vertical moving,and ensure that small animals stay in the same posture in the scanning process.The system is carefully designed to acquire both photoacoustic and fluorescence signals in a same device,and further provide a system tool for biomedical basic research and algorithm development.The photoacoustic and optical fusion probes are developed and analyzed through experiments.The photoacoustic and optical fusion probes are also essential for the imaging fusion studies.In this thesis,we synthesized the ICG-loaded Au@Si O2 nanoparticle as a dual-modality contrast agent for PAI and FMI.The probe was uniquely designed consisting of gold nanorod cores and ICG with silica shell spacer layers to prevent signal quenching effect.It was observed that ICG-loaded Au@Si O2 nanoparticles exhibited low cytotoxicity and could retain photophysical properties in the near infrared region.We applied the probe on both tumor and ischemia mouse models,and tested its tumor and ischemia targeting and imaging capability by using both photoacoustic and fluorescence imaging modalities.The study revealed promising results of our devised nanoparticle for effective and specific tumor and ischemia targeting.Furthermore,the combination of PAI and FMI using our ICG-loaded Au@Si O2 nanoparticles exhibited superior advantages for precise diagnosis in different scenarios.Both modalities can confirm each other's findings in tumor detection,and more interestingly,they were able to achieve fast ischemia detection and precise classification of the ischemia severity,which holds great potential for early diagnosis of ischemic legs.The multi-modal imaging method was applied to the early detection of hepatocellular carcinoma.Multi-mode imaging fusion is an effective way to solve the limitations of each imaging modality,and is the trend of biomedical imaging.Early diagnosis of the tumor is of great significance.In this thesis,we using NIRF/MRI/PAI triple modality image demonstrated that M-HFn based nanoprobes could image the Hep G2 tumor cells before they formed solid tissues.This research is benefit the early detection of tumor.