Acoustic-spectrum-compensated Functional Photoacoustic Microscopy With Fiber Optic Ultrasound Sensor

Photoacoustic microscopy(PAM)can image absorbers in a biological tissue at the subcellular resolution,based on which blood oxygen metabolism and functional abnormalities of the tissue can be visualized.PAM provides a powerful imaging modality for basic life sciences and diagnostic applications.However,hindered by the detection capability of the ultrasonic detection element—the piezoelectric transducer,the functional imaging capability of the existing miniaturized photoacoustic microscope is insufficient.As a result,the uses of PAM in wearable instrumentation and endoscopic imaging were limited.Aiming at this problem,this thesis has thoroughly studied the limiting factors of the functional imaging capabilities of PAM,and proposed an ultrasound-spectrum compensation technique to improve the accuracy of blood oxygen saturation measurement.Further,a miniaturized optical-fiber-based ultrasound sensor with high sensitivity and broad bandwidth was used to build a PAM for functional imaging of cerebral and rectal vessels,respectively.The main researches of this thesis are as follows:(1)The limiting factors of the functional PAM are investigated,based on which the ultrasound-spectrum compensation technique was proposed to improve the accuracy of blood oxygen saturation measurement and imaging.A theoretical model of photoacoustic excitation and detection in the frequency domain was established,and the influence of factors such as the size of the absorbers,the pulse width of the excitation light,and the frequency response of the ultrasonic sensor on the measurement of blood oxygen saturation was quantitatively analyzed.The study found that: an ultrasound transducer with a specific bandwidth has a selective enhancement effect for blood vessels with matching sizes;at the same time,the pulse width of the excitation light also affects the spectrum of the photoacoustic signal.These factors all adversely affect the accuracy of blood oxygen saturation measurement.These influences can be overcome by performing an ultrasonic-spectrum compensation,which is independent on the blood vessel diameter and pulse width.The blood oxygen saturation measurement result before compensation deviates from the true value by 15%,and after compensation,the measurement result is very close to the true value.(2)A miniature photoacoustic microscope was realized based on a broadband,highsensitivity fiber optic ultrasonic sensor,and high-resolution photoacoustic functional imaging was performed on the brain tissue of living animals and the blood vessels of the rectum.The theoretical model found that a broad detection bandwidth can overcome the "invalid information" at low frequencies and effectively collect the changes in blood oxygen saturation at higher frequencies.With this theoretical guidance,a fiber-optic ultrasonic sensor with a diameter of 58 ?m and an effective bandwidth of 40 MHz was prepared by chemical etching to form a miniatured PAM.The oxygen saturation of the cerebral vessels was in vivo imaged.Further,a functional photoacoustic endoscope with an outer diameter of only 2.3 mm was implemented,with lateral resolution of 15?m.