A Wearable Photoacoustic Microscopy For Investigation Of Brain Imaging

The studies of neural activities and hemodynamics are two important research directions in modern brain science for studying brain functions.Currently,some optical imaging technologies like fluorescent microscopy,two-photon microscopy and threephoton microscopy have achieved high-resolution neural imaging both in anesthetized,awake and freely moving animals,realizing the visualization of neurons and the neural activities.By neuroimaging,previous studies reveal the important role of neural activity and neural circuit communication in brain activities,and characterize the structure and function of brain.On the other hand,the cerebrovascular network is the most important place to provide nutrient,transfer small molecule,exchange oxygen for keeping brain normal work and maintaining the physiological balance of brain.When the brain occurs drastic activities or suffers some functional disorders,it will not only cause abnormal neural activities,but also affect the brain hemodynamics,which may lead to serious neurovascular diseases.Therefore,besides the study of neural activities,it is of great significance to study the brain hemodynamics and obtain the structural/functional information of the brain vascular network.It is also important to the study of various brain functional diseases such as brain tumor,cerebral ischemia,stroke,vascular dementia,epilepsy and so on.Photoacoustic microscopy,combining the optical imaging and ultrasound imaging modalities,is a new hybrid imaging technology,with the characteristics of high resolution,high contrast and deep penetration depth.Due to the strong intrinsic optical absorption of hemoglobin,photoacoustic microscopy can achieve unlabeled,high-resolution imaging of brain vasculature at capillary level,which shows a great potential of studying brain hemodynamics.Until now,various photoacoustic microscopic imaging techniques based on motor scanning,galvanoscope scanning and micro-electro-mechanical(MEMS)scanning have achieved abundant researches in the study of structural and functional brain hemodynamics in small animals.However,existing photoacoustic microscopies still have the limitations of complex structure,large volume size and heavy weight.The current researches of brain hemodynamics are mainly in anesthetized or head-restrained animals.Realizing the high-resolution brain vascular imaging under awake and freely moving condition is still a big challenge.In this dissertation,we would like to develop a wearable photoacoustic microscopy,which has great characteristics of high resolution,fast imaging speed and large field of view.It can help us observe the real-time changes of local brain hemodynamics,and obtain the structural/functional information of brain,with animal under awake and freely moving condition.In order to realize above goals,we firstly focused on the study of developing miniaturized photoacoustic microscope.We proposed an electro-thermal MEMS-based optical scanning strategy,employed the miniaturized optical/acoustic components for structural design,and wrote a synchronous acquisition program.We successfully reduced the volume size and weight of traditional photoacoustic microscopy system,and developed an ultra-compact hand-held photoacoustic microscope.The handheld device had characteristics of small size,light weight and high spatial-temporal resolution.It was the first step to realize the miniaturization of photoacoustic microscopy,and achieve wearable imaging.We applied it to carry out multi-organ imaging of small animals and oral mucosa imaging of human.Then,we further optimized the structure of hand-held photoacoustic microscope,developed a wearable photoacoustic microscope and a two modality photoacoustic/EEG microscope,which were suitable for cerebrovascular imaging in behaving rats.We made an ischemia model and a localized acute seizure model for investigating the brain hemodynamics and neurovascular coupling.Finally,we developed a miniaturized wearable photoacoustic microscope for brain imaging in freely moving mice.Compared with previous devices,the new microscope had a similar lateral resolution,smaller volume size,lighter weight,lager field of view,and more stable imaging performance.We used the new mini device to carry out the short-term(40 minutes)and long-term(7 days)brain imaging in freely moving mice.In summary,we proposed a series of miniaturized hand-held and wearable photoacoustic microscopes,and applied them to animal and human studies.Especially,by using the developed wearable imaging devices,we successfully extended brain studies from anesthetized or head-restrained animals to awake and freely moving animals,and obtained the structural and functional information with animal under various physiological states.It was of great importance to guiding the study of brain functional disorders,neurovascular degenerative diseases,brain cognition and brain behavior.