| The brain has long been considered an extremely complex system in structure and function,with significant changes in the cellular structure and connectivity of brain regions every few millimeters.Functional diseases of the brain occur primarily due to the loss of neurons in different brain nuclei,or disturbances within the nuclei and the neural circuits they form in multiple brain regions.Transcranial focused ultrasound for neuromodulation and stimulation,as an emerging technique for the treatment of functional diseases of the brain,offers a potential therapeutic tool in the field of neuroscience due to its non-invasiveness,penetrability,and spatial specificity.However,most existing studies have focused on single-target stimulation of brain neurons using single-element focused transducers,which cannot flexibly control the size and position of focal spots,as well as achieve multi-target ultrasound stimulation.Therefore,in order to advance the research of multi-target ultrasound stimulation in animal models,in this study,a multi-target transcranial ultrasound phased system was developed using a two-dimensional powered array transducer to provide an effective research platform for evaluating the feasibility of multi-target ultrasound stimulation treatment protocols.The main contents are as follows:(1)Based on a multi-modal anatomical model of the human head,the acoustic model of the skull and heterogeneous brain soft tissue was constructed.Through 3-D acoustic simulations,the concave array transducer was designed and optimized.The effects of the skull and soft tissues on the acoustic pressure field were examined using the simulations of transcranial ultrasound propagation.The comparisons between the fluid and elastic simulations were used to evaluate the influence of mode conversion and shear wave attenuation in the skull.(2)Considering the volume,thickness,and other characteristics of the rat skull,the type,center frequency,element size,and the number of the array transducer were determined.The material properties of the passive acoustic layers were measured,and a miniaturized two-dimensional powered array transducer was fabricated.An FPGA-based multi-channel pulse drive system was used to excite the array elements of the transducer to achieve accurate delay control and provide sufficient output power.A multi-target ultrasound system was developed with the array transducer,pulse drive system,and hydrophone acquisition system.(3)Acoustic models were established using computerized tomography to assess the effects of varying the axial positions,interval distances,and the number of foci on key parameters such as the peak full width half maximum(FWHM),acoustic pressure,amplitude ratio of the main and side lobes,and the error in the peak position.The multi-focal spot acoustic field was shown to be more complex focusing characteristics than the single-focal spot acoustic field due to the superposition of each focal spot and the different volume of focal spots.The minimum distance between the two-6 d B focal spots and the FWHM was positively correlated with axial focusing position;the relative changes in focal properties were similar for each axial position.(4)To evaluate the acoustic performance of the array transducer,the acoustic pressure field was measured using a fiber-optic hydrophone.The maximum acoustic pressure and spatial average intensity in free water were 2.21 MPa and 133 W/cm~2,respectively.The simulated and experimental results were compared,and good agreement was found for both the peak position and the focus shape.It was evident that the ultrasound system is capable of generating multiple focal spots simultaneously in the 3-D intracranial field and precisely controlling the focus position.Finally,in vivo stimulation experiments on rats and histological analysis of brain sections by H&E staining demonstrated that the multi-target transcranial focused ultrasound phased system does not cause damage or significant hemorrhage to the brain. |
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