Development Of Functional Optical Coherence Tomography And Its Applications In Stroke

Ischemic stroke happens when blood flow to a part of the brain is stopped either by a blockage,which is characterized with high morbidity,high disability rate,high mortality,high recurrence rate and high economic burden.Insufficient energy supply after ischemia leads to cell death and tissue damage,which eventually leads to dysfunction and even death.Traditional brain imaging techniques may have many disadvantages such as high cost,low resolution and harmful to human body.Optical coherence tomography(OCT)is an emerging three-dimensional optical imaging modality with the advantages of non-invasive,high-sensitivity and micrometer-scale-resolution.With the combination of OCT and dynamic scattering analysis,OCT angiography(OCTA)employs the movement of red blood cells as the endogenous label for blood flow to obtain three-dimensional(3D)dynamic blood flow information.OCT-based optical attenuation coefficient(OAC)can be used to assess tissue damage and reveal tissue activity accurately by analyzing signal attenuation characteristics.Spectral analysis with visible light OCT enables measurement of saturation oxygen.Combing OCT structure,blood perfusion,tissue viability and saturation oxygen information,functional OCT is helpful to further understand the ischemic mechanism and provides an effective tool for treatment assessment and drug screening.In this thesis,spatio-temporal analysis was made with the rat photothrombosis(PT)stroke model using the OCT functional imaging techniques.The main works are summarized as follows:Firstly,a system integrated PT module and OCT functional imaging system.Based on the photochemical reaction between 532 nm laser and rose-bengal,stroke model with accurate positioning and controllable ischemia range can be achieved.OCT module used the 1325nm fiber-based SD-OCT system,achieving the large penetration depth in the highly-scattering brain tissue.With the highly stable phase information of the spectrometer,the high sensitive capillary level blood flow imaging can be realized.SD-OCT achieved the axial resolution of 7.6 ?m,the lateral resolution of 21 ?m,the imaging depth of 2.3 mm and the fast line scan rate of 90 kHz.And integrated system enabled the real-time monitoring of PT and ensured the consistency between different animals.Secondly,with the high sensitivity OCTA algorithm combing the motion,intensity and morphology information,the long-term,in vivo study was performed the in the rat PT stroke model,including the acute stroke period and the chronic period.In the acute period,the ischemic area increased and reached the maximum at Day 3.In the chronic period of Day 4-13,blood reperfusion occurred mainly in the distal middle cerebral arteries and the pial microvessels.There was no reperfusion observed in the deep capillaries in the male rats,while low degree reperfusion occurred in the female rats.The results demonstrated the spatio-temporal dynamics of blood perfusion and the gender difference.Based on OCT A,on the blood perfusion mechanism,including the PT process,the acute phase after stroke and the chronic recovery phase.3D quantitative analysis was performed on different blood vessel types using OCTA,including large blood vessels,pial microvessels,and deep capillaries.Long-term quantitative analysis of superficial and deep blood flow perfusion was also performed on male and female rats.A comparative study was conducted to further understand the mechanism of cerebral blood flow perfusion.The hybrid division multiplexing(HDM)method was proposed,combining spectral segmentation and spatial modulation spectral segmentation,to acquire multiple independent subsamples technique.Then,long-term,in vivo studies of tissue damage mechanism in the rat PT stroke model was performed with OAC spatiotemporally.After PT,the damaged area reached to the maximum at Day 3,and only recovered partially in the following days.Furthermore,the cellular mechanism that causes OAC change was explored with NeuN and GFAP immunohistochemical staining.The change of OAC was highly correlated with the increase of astrocytes and the death of neurons.At the border of the ischemic-penumbra region and the recovered penumbra region,the correlation coefficient was 92.6%between the change in OAC and the increase of astrocytes,and the correlation coefficient was 91.3%between the change in OAC and the decrease of neuronal cells.Lastly,a visible light OCT system based on a supercontinuum source was designed and developed for label-free OCTA and saturation oxygen measurement.With the visible light of 500-650 nm,the spectral difference of the oxyhemoglobin and oxygen-deficient hemoglobin was analyzed to measure saturation oxygen.Based on OCTA information,saturation oxygen is helpful to differentiate the vein and artery,and assess the blood oxygen metabolizing.The system integrated PT module and OCT functional imaging system,and provided real-time monitoring and feedback in the PT progression.OCTA blood perfusion demonstrated that blood reperfusion mainly occurred in the large vessels and pial microvessels;however,the reperfusion level of deep capillary was low.Optical attenuation coefficient results demonstrated that there was still unrecovered tissue damage in end of the chronic period,and the increase of attenuation coefficient in the damaged area was closely related to the death of neurons and the increase of astrocytes.Visible light OCT can extract blood oxygen saturation information,to distinguish arteriovenous vessels and evaluate blood oxygen metabolism level after stroke.OCT and its functional imaging provide a multi-parameter imaging platform for understand the stroke mechanism and provide the objective evaluation of treatment options and drug development.