Optical-resolution Photoacoustic Microscopy For Early-stage Oral Cancer Detection

Oral cancer is a common malignant tumor in head and neck of human body.Early-stage oral cancer lacks obvious symptoms,which make it very hard for the patients to be aware of,or for normal medical examinations to detect.That is why most oral cancer patients are in advanced stages at the time of detection.Due to cancer metastasis,late stage oral caner is very hard to be cured,making it a lethal threat to human health.Therefore at early-stage screening is a better option to improve the five year survive rate of oral cancer patients.Recent studies have shown that the capillary loops on the oral mucosa in the cancer region will show obvious morphological changes in the early-stage oral cancer.Hence it is possible for us to detect early-stage oral cancers by imaging these capillary loops and examine their morphological features.Unfortunately,traditional medical imaging techniques have low sensitivity to blood.The morphological changes of capillary loops on oral mucosa will not be detected effectively.Fortunately,an emerging non-invasive,high resolution,and high contrast imaging technique,optical resolution photoacoustic microscopy(ORPAM),comes out.This new imaging modality employs well focused modulated or pulsed laser to illuminate imaging target to generate ultrasound waves,which are referred to as photoacoustic(PA)signals.By detecting these PA signals,the structural or functional information of the imaging target will be obtained.In ORPAM,the image contrast is based on optical absorption.By using the multispectral strategy ORPAM is able to image the corresponding absorber inside the bio-tissue,which provides high imaging specificity for ORPAM.Due to the low attenuation of ultrasound inside bio-tissue,the imaging depth of ORPAM is deeper than other pure optical imaging modalities,such as confocal microscopy,fluorescence imaging and two-photon microscopy.Besides,no ionized radiation is employed during the imaging process.These features make it suitable for imaging blood vessels,especially capillary loops.Therefore,using ORPAM to image the capillary loops offers a new method for detecting early-stage oral cancer.and sets up a new application field for ORPAM.However,traditional ORPAM systems have many disadvantages and cannot be applied for oral imaging directly including low scanning speed,bulky size,lack of flexibility and et al.Thus,the application of ORPAM is limited to small animal studiesand very few human body imaging results are reported.Based on the above discussions,we develop an ORPAM system suitable for imaging human oral cavity in this dissertation.First,we introduce the basic principles of photoacoustic effect followed by system configurations,scanning mechanisms and system performance.Then,we report the use a rotary scanning mechanism to develop a portable ORPAM and apply it to image capillary loops in the human oral cavity.Furthermore,a miniaturized hand-held ORPAM probe more suitable for imaging the entire oral cavity is fabricated and assembled.The main content of this paper includes:1,A transmission-ORPAM system based on mechanical-scanning is designed and assembled.The acquisition program and image reconstruction algorithm are introduced.2,A rotary scanning method,which is able to eliminate the relative movement between the imaging interface and the target,is realized based on galvanometer system and cylindrically focused ultrasound transducer.3,The imaging interface of ORPAM is modified to meet the requirements of human oral imaging.Meanwhile,experiments covering from bio-tissue phantom,in vivo mouse ears and brains,small animal tumor model and human lips and tongues are conducted.The imaging results indicate that this method holds great feasibility and potential for screening early-stage oral cancer.4,A miniaturized ORPAM probe based on microelectromechanical systems(MEMS)mirror is developed for imaging entire oral cavity.After a serious of experimental verifications,high resolution and high contrast images of capillary loops inside human oral cavity are obtained.The experimental and theoretical results in this paper fully demonstrate the feasibility of ORPAM for early-stage oral cancer detection,which reveal a solid foundation for the development and promotion of clinical trials.In order to meet the requirements of human oral imaging,this paper propose a new scanning mechanism and imaging interface of ORPAM system,improves its adaptability for various targets,expands the scopes of ORPAM has opened up a new clinical door for ORPAM.