The Study Of Microvascular Imaging Based On OCT And MPM

Blood circulation plays an important role in regulating metabolism and immune function in organisms,so the physiological state of blood circulation can reflect the health status of biological tissues or organs.In clinical medicine,angiography can provide an effective diagnostic basis for disease diagnosis.Cerebral vascular structure,distribution and cerebral blood flow and other parameters are closely related to cerebrovascular diseases and are important indicators of cerebral vascular diseases.The growth and proliferation of tumors are closely related to the changes of blood vessels and the formation of new blood vessels.If the shape and changes of neovascularization can be observed clearly,then the tumor therapy and metastatic monitoring can be achieved.Therefore,realizing the imaging of cerebral vascular distribution and tumor blood vessel monitoring,especially the microangiography are of great significance to disease diagnosis,research and drug screening.With the rapid development of optics,electricity,mechanical manufacturing and other related technologies,various imaging techniques have been developed and applied.The commonly used imaging techniques in angiography and disease diagnosis are computed tomography(CT),magnetic resonance imaging(MRI),optical coherence tomography(OCT),nonlinear optical imaging,etc.Because of the difference of imaging mechanism and operating system,these imaging techniques have their specific research objects and application fileds.Among numerous imaging techniques,OCT has high-imaging depth,high-resolution and rapid 3D in vivo imaging ability,and multi-photon microscopy(MPM)has high-resolution and excellent sensitivity.Both have greatly attracted extensive research and been widely used due to their outstanding advantages.In the meanwhile,the emergence of new multifunctional nanomaterials has promoted the development and application of optical imaging contrast agents,and further improved the imaging quality and application fields of optical imaging technology.In recent years,OCT imaging technology and a variety of contrast agents have been used in the study of microvascular imaging,however,the resolution,sensitivity and specificity of present OCT limit the development of its development and application.To solve this problem,in this thesis,we developed new nanomaterials as microvascular imaging contrast agents,and combined the imaging advantages of OCT and MPM.We studied the microvessels of cerebral cortex in mice in different ways to develop new experimental methods for analyzing brain activity,brain disease research and drug development.At the same time,we constructed the tumor model of the skin ridge of nude mice,achieved the imaging and monitoring of vascular changes during the tumor growth process under the dual system,so as to further realize the research of tumor growth mechanism.The main work of this thesis is summarized as follows:1.On the basis of extensive research on OCT and MPM,we built the SD-OCT system and MPM system with consideration of the experimental research needs,and carried out the system stability testing and system optimization.We reduced the noise by using block-matching 3D(BM3D),and used Amira software to reconstruct the OCT images from 2D to 3D,to obtain a visual image with high resolution.In order to overcome the laser transmission jitter and uneven light spot existing MPM system,we coupled the laser through the optical fiber so as to achieve a more even and brighter spot,and higher stability in the imaging process for obtaining a clear high-resolution multi-photon image.2.According to the experimental scheme,we prepared functional nanomaterials with low biotoxicity,good stability and biocompatibility considering the system parameter setting and imaging needs of OCT and MPM,including polyethylene glycol(PEG)ylated gold nanorods(GNRs)(PEG-GNRs)and semiconducting polymer nanoparticles(SPNs),then performed physical and optical characterization and cytotoxicity test to make them suitable as the imaging agents for OCT and MPM imaging.3.OCT and MPM imaging of vascular were performed.We used functional nanomaterials as OCT and MPM imaging agents,performed cerebral cortex angiography in vivo in the mouse craniotomy model,and the images contrast were enhanced by 5.87 dB,at the same time,dynamically monitored the changes of the contrast agent in the cerebral blood vessels in mice.We also constructed the tumor model of the skin ridge of nude mice,monitored and imaged the vascular changes during tumor growth under the dual system.The innovation of this thesis is summarized as follows:1.SD-OCT and MPM systems have been built and optimized to achieve high-resolution cerebrovascular imaging in living mice from different angles,combining functional contrast agents.2.Using the above two imaging systems,the monitoring of angiogenesis during tumor growth in living mice was achieved,which is of great significance for the study of microangiography and disease diagnosis in vivo.