Thermoacoustic Imaging And Its Application In The Brain Diseases Detection

Brain among all organs has the most complex structure and functions in the body.Despite its importance,our knowledge of the brain is very limited.One of the major obstacles that preclude rapid advancements of the studies on brain is the lack of highresolution imaging techniques that would be suitable for neuroimaging.In 2013,the United States launched the national project of “Brain Research through Advancing Innovative Neurotechnologies”(BRAIN),aiming to help researchers to uncover the mysteries of brain disorder.After that,the European Union,Japan,Australia,South Korea and China have all initiated their own Brain Project.One of the major goals of the Brain Project is to develop novel imaging technologies,tools and approaches which would provide more structural and functional information of brain to help researchers and scientists to understand the underlying mechanism and physiopathology of brain disorders.Microwave-induced thermoacoustic imaging(MI-TAI)combining the high acoustic resolution and deep microwave penetration depth,delivers great potential in non-ionized,non-invasive,real-time imaging of the whole brain with high spatial resolution.MI-TAI utilizes the tissue-specific absorption rate(SAR)as a source of endogenous contrast.When the electric field distributed evenly in tissue,MI-TAI could map the conductivity of brain tissue,while offering high spatial and temporal resolution.As researchers suggested,the conductivity of brain tissue is highly correlated with the brain activities and physiopathology of brain disorders.Thus,MI-TAI could provide essential information for understanding brain functions and disorders.However,to date,there are no literature reporting in-vivo brain imaging using MI-TAI.As an important preclinical study,in-vivo MI-TAI in the animal brain would validate its feasibility in human brain imaging.Rodents,which provides various brain disease models,are the most commonly used animals in studying physiopathology of human brain disorders.Therefore,the aim of this dissertation is to develop MI-TAI for in-vivo rat brain imaging as a preclinical step toward imaging human brain.Based on this goal,a novel MI-TAI approach was developed.The new approach eliminated the scattering effect induced by using film and coupling media.In addition,instead of using transformer oil,deionized water was used to improve the coupling efficiency of microwave.In the end,two MI-TAI systems were designed and built in this dissertation,and MI-TAI imaging of in-vivo rat brain was achieved for the first time in both coronal and transverse sections,demonstrating the feasibility of in-vivo MI-TAI brain imaging.The ability to use MI-TAI to monitor neonatal intraventricular hemorrhage and thermal damage of high intensity focused ultrasound(HIFU)was also demonstrated in this dissertation.In addition to developing novel MI-TAI systems for imaging brain diseases,a thermoacoustic and ultrasound dual-modality technique and a novel high contrast needle visualization technique were developed in this dissertation.The development of these novel techniques would advance the MI-TAI technology and extend the areas of its applications.The innovations of this dissertation are summarized as follows:1.Designed and built two MI-TAI systems.Based on the goal of in-vivo rat brain imaging,a 1GHz MI-TAI system and a 3.05 GHz MI-TAI system were designed and built in this dissertation.The novelties include the design of a microwave system,ultrasound system,water-proof breathing masks for rat and mouse,etc.2.Conducted brain study using the MI-TAI systems.Demonstrated for the first time that relative permittivity of tissue can also provide contrast in MI-TAI.A method of fabricating a realistic rat brain phantom model was developed and was used for studying the effect of skull on MI-TAI brain imaging.For the first time,high-resolution MI-TAI of in-vivo rat brain was achieved in coronal and transverse sections.The potential of MITAI for non-ionized non-invasive monitoring neonatal hemorrhage and thermal damage of HIFU was proved in murine models.3.A novel technique of thermoacoustic and ultrasound dual-modality was developed.This technique was based on exciting the sample and ultrasound transducer simultaneously using microwave,which realized TAI and ultrasound imaging without additional ultrasound generating systems.4.A novel approach was established based on electromagnetic induction and thermoacoustic effect for visualization of needle in tissue with high contrast and high resolution,which overcomes the limitations and drawbacks of current clinical imaging techniques like CT and ultrasound in needle visualization.In this dissertation,two novel MI-TAI systems were designed and built,and highresolution in-vivo rat brain imaging was achieved for the first time.The potential of MITAI in detecting and investigating brain diseases was proved in the in-vivo murine models of neonatal intraventricular hemorrhage and thermal damage monitoring of HIFU.In addition,the novel dual-modality technique developed in this dissertation for high contrast needle visualization in tissue would extend the research and clinical applications of MI-TAI.