The Study Of Photoacoustic Technology In The Diagnosis Of Crohn's Disease

This thesis focused on the research of photoacoustic imaging in Crohn's disease.It mainly included four aspects: the study of multispectral photoacoustic imaging in Crohn's disease animal models,the multispectral photoacoustic imaging in human Crohn's disease,the study of strain-photoacoustic imaging in Crohn's disease animal model,and study of endoscopic photoacoustic imaging in Crohn's disease.In this thesis,after introducing the theoretical background,the preparation and exploration of preliminary clinical research,use of multispectral imaging in Crohn's disease animal models was discussed.Multispectral imaging is a unique advantage of photoacoustic imaging and can provide molecular information.In this study,using multiple wavelengths was proposed to detect the two key molecular contents:hemoglobin and collagen to reflect pathological features.The setup equipment included a programmable,scientific research ultrasound imaging platform working under independently developed functional scripts and an OPO laser.With the laser employed,the system had photoacoustic and ultrasound dual-mode imaging functions and was used for animal Crohn's disease research.The experiment mainly included two parts,one part was using the minimally invasive lighting method in vivo,which can avoid the problem of light attenuation,but required the insertion of optical fibers into the body causing minimally invasive.The second part was using the non-invasive external illumination method.The optical energy was optimized by spatially arranging optical fibers to meet the imaging requirements.The results showed that multispectral imaging can successfully help diagnose and distinguish subjects between acute and chronic Crohn's disease.Furthermore,I advanced my work to the stage of patient research in clinic.However,the use of multi-spectral imaging methods met a great challenge in patients research because the location of the patient's lesion is often unknown and is generally a few centimeters deep under the skin.Besides the imaging depth challenge,the second challenge is that the patient's condition is often more complicated and cannot be distinguished by simple acute and chronic enteritis.More often,it is a mixture of both.And the irregular intestinal peristalsis has a certain effect on the stability of imaging.Therefore,in the experiment,a special low-frequency abdominal ultrasound probe was used to reduce signal loss,improving the signal-to-noise ratio and imaging depth.The deepest imaging depth reached 6 cm,to meet most of the cases.After that,each patient image taken was analyzed and confirmed in combination with clinical diagnosis.Because the abdominal skin,fat,muscle thickness,etc.between individuals will affect the quantitative standard,so only the key features were observed in this study.For example,the photoacoustic signal at 1310 nm wavelength reflects collagen content.If the signal is relatively strong,it means that the patient has the characteristics of chronic fibrotic enteritis.After the experiment and clinical pathological section,CT,Doppler ultrasound,and other methods that have been clinically applied to validate.It was found that the multispectral photoacoustic imaging method can accurately reflect the patient's Crohn's disease.In the experiment,it was found that Crohn's disease was not only related to the molecular content of hemoglobin and collagen,but also directly affected the elasticity of intestinal wall tissue.Therefore,I proposed the elastic-photoacoustic theory to solve the diagnosis and differentiation of Crohn's disease from another angle.Strainphotoacoustic was the innovative idea proposed for the first time.Its purpose was to use the method of photoacoustic imaging to measure the elasticity of biological tissues.In vivo measurement of biological tissue elasticity was a scientific research problem for a long time because it is difficult to directly measure the stress of the tissue in deep.The use of skin and other surface stress instead will bring great errors and cannot meet the demand.The idea of strain-photoacoustic imaging was to replace the stress measurement with photoacoustic signal change measurement.Based on the deformation theory of blood vessels and some empirical formulas,I derived the relationship between the elasticity(similar with Young's modulus)and the change and deformation of the photoacoustic signal.In other words,the elasticity of the tissue can be obtained by measuring the change of the photoacoustic signal and the deformation of the tissue.Strain-photoacoustic imaging was verified in the Crohn's disease animal model.The experimental results showed that the acute inflammation of Young's modulus measured by strain-photoacoustic was about one-half of that in chronic inflammation,which was the same as that obtained from in vitro measurements.The final research in this paper was to promote the integration of in vivo measurement methods into endoscopic photoacoustic imaging.There are two main advantages.First,endoscopic imaging is foremost compatible with colonoscopy imagers currently used in clinical.The instrument channel of the colonoscopy imager can provide space for photoacoustic imaging,replacing the original tissue biopsy needle.Second,the endoscopic imaging method does not need to consider the attenuation of light by the skin,muscle,and fat layer,and can realize image quantization with simple process.Based on the intracardiac ultrasound imaging array produced by Siemens,I designed a balloon-type photoacoustic imaging probe.The balloon-type probe combined with the ultrasound array,side-emitting optical fiber,water injection equipment,etc.,which can realize multispectral photoacoustic imaging.In the experiment,the Crohn's disease animal model was employed.The balloon-type probe was used to image mice with different diseases conditions.Through quantitative analysis of the image,it can successfully distinguish subjects between individuals with acute enteritis and chronic enteritis.The results were then validated by disease conditions based on the pathology results.