| Part 1 Establishment of a model of acute local cerebral ischemiain monkeys Background: Cerebral ischemia has a high incidence,disability and mortality,which is a serious threat to human health.Establishing an animal model of cerebral ischemia that is most consistent with clinical features is of great significance for its pathological changes and clinical research.Currently,research on cerebral ischemia models is mainly based on rodents,rabbits and dogs.Monkeys are close to humans,but because of the complexity of the purchase process,the high cost,the high requirements for intervention and inspection,and the high cost of medicines and equipment,they are used less in modeling.Clinically,the incidence of cerebral ischemia is mainly caused by thromboembolism,and about 85% of them occur in the middle cerebral artery(MCA).Therefore,it is essential and necessary to establish an ideal animal model of cerebral ischemia,reflecting the clinical characteristics of the human body.Objective: To establish a model of local acute cerebral ischemia in rhesus monkeys,and to provide an ideal experimental model and research method for early diagnosis,treatment and evaluation of cerebral ischemia.Methods: Eight healthy rhesus monkeys were selected.CT scan and interventional angiography were performed before surgery to exclude cerebrovascular and intracranial lesions and to evaluate blood vessels and their appearance.Under DSA guidance and monitoring,the microcatheter was inserted into the MCA M1 branch via the femoral artery,and autologous white thrombus was introduced to block blood flow.Immediately after embolization and 24 hours after embolization,DSA and MRI imaging were used for evaluation.After embolization for 24 hours,2 monkeys were sacrificed,perfused and fixed.Two weeks later,the brain was taken for pathological examination.Results: Seven rhesus monkey models of cerebral ischemia were successfully established and one died during intubation.After successful modeling,autologous white thrombus was introduced into the MCA M1 segment,blood flow was blocked,and cerebral ischemia was formed at the corresponding site.Immediately after embolization and 24 h after embolization,DSA and MRA showed MCA occlusion,and MRI multiple sequence imaging showed acute focal cerebral ischemia.Pathological gross specimens and HE staining showed deep brain tissue infarction lesions,thrombus was seen in MCA branches,and the boundary between infarcts and normal brain tissue was clear.Conclusion: The autologous thromboembolism method can establish an ideal and effective model of monkey cerebral ischemia,which has important application value in the related basic and clinical research of cerebral ischemia.MRI and DSA can evaluate the modeling effect to ensure the accuracy and effectiveness of the modeling.Part 2 The role of ultrasound in the model of acute cerebral ischemiain monkeys Background: The development of ultrasound imaging is rapid,and the role of ultrasound imaging technology in the diagnosis and treatment of cerebrovascular diseases is also becoming more and more important.New types of ultrasound techniques such as brain contrast imaging,two-dimensional doppler imaging,energy doppler imaging,and three-dimensional imaging of the brain provide new valuable tools for the study of cerebrovascular diseases.For many years in clinical practice,the judgment of craniocerebral vascular lesions has been mostly performed by DSA,CT and MRI.Although DSA is the "gold standard" for the diagnosis of ischemic cerebrovascular disease,it is traumatic and multi-interventional;conventional MRI can not find small infarcts,especially in the 6 hours of onset,and is not portable.In addition,it often can not be combined with bedside diagnosis and treatment.Therefore,we used ultrasound to diagnose the animal model of cerebral embolism and explore its role in the detection and evaluation of cerebral embolism.Due to the different biological characteristics of rhesus monkeys and humans,such as small size,thin intracranial blood vessels and small thickness of the humerus,and considering the characteristics of insufficient acoustic bone windows(IABW),in this chapter,transcranial color-coded sonography(TCCS)and contrast-enhanced transcranial sonography(CE-TS)were performed before and after modeling to explore ultrasound in acute imaging characteristics and evaluation in the model of cerebral ischemia.Objective: To investigate the role of ultrasound in the examination of local cerebral ischemia in rhesus monkeys.Methods: Eight healthy rhesus monkeys were selected.CT scan and interventional angiography were performed before operation to exclude cerebrovascular and intracranial lesions and to evaluate blood vessels and their appearance.The model establishment method was the same as the experiment Part 1.The monkey was placed in the lateral position,and the sacral window was selected as the translucent window.TCCS and CE-TS were performed to treat the monkey.The intracranial blood vessels before and after modeling were evaluated.Results: Before embolization,TCCS clearly showed MCA,and its blood flow was good,and the normal low-resistance MCA spectrum was recorded.CE-TS showed that the contrast agent was well filled,not only showed MCA,but also showed clear and complete cerebral arterial circle.After embolization,TCCS showed no significant blood flow signal,and the normal arterial spectrum was not recorded;CE-TS showed a local contrast filling defect in the middle cerebral artery.Pathological gross specimens and HE staining showed deep brain tissue infarction lesions,thrombus was seen in the middle cerebral artery branches,and the boundary between infarcts and normal brain tissue was clear.Conclusion: TCCS and CE-TS can evaluate intracranial aorta in real time and dynamically.In the case of cerebral embolism,rapid and convenient diagnosis and evaluation can be given,and it has practical clinical value in the study of cerebral ischemic diseases.Part 3 Preliminary study on the application of ultrasound withsuper-resolution imaging in monkey cerebrovascular(Joint research results of cooperation with Xi'an Jiaotong University)Background: From experiment Part 2,ultrasound only showed to be ideal for large blood vessels in the brain,and appeared poor results for tiny blood vessels and terminal blood vessels in the brain.Even with the enhancement of contrast agents,imaging was still not ideal.In recent years,super-resolution imaging technology has made significant progress in theory.At present,the most commonly internationally used ultra-fast plane wave ultrasound doppler brain function imaging[1] and ultrasound-based microbubble-based super-resolution imaging technology[2] have been advanced to the small blood vessels and blood flow of small animals such as mice.But imaging of tiny blood vessels in monkeys and larger living animals has not yet been performed.In China,super-resolution imaging technology has achieved some preliminary research results.However,it has few basic experiments and clinical experiments in large animals.Therefore,in recent years,we have conducted joint research with Xi'an Jiaotong University to try to explore the application and performance evaluation of this new technology in the diagnosis of large animal cerebrovascular diseases.Objective: To image the intracranial blood vessels of rhesus monkeys by super-resolution microbubble imaging technique,and to explore its imaging characteristics and imaging advantages compared with traditional transcranial ultrasound.Methods: Firstly,the validity and feasibility of super-resolution imaging technique were verified by phantom simulation experiment.Based on the in vitro experiment,the imaging parameters were adjusted accordingly.Finally,two rhesus monkeys were used for live brain microvascular imaging experiments.Results: In vitro experiments,it showed that the computational complexity of superresolution imaging was significantly reduced compared with the traditional ultra-fast active cavitation imaging synthesized by the characteristic space adaptive beam,the axial resolution gain was increased by 3 times,and the cavitation organization ratio was increased by 2d B;compared with conventional plane wave imaging,super-resolution imaging can identify the tiny diameter of the brain micro-vascular to 1mm,or even 0.7mm,and can extract its blood flow information.At the same time,the contrast-to-noise ratio was increased by 5.625 d B and the resolution was increased by approximately 30 times.The results of the rhesus monkey experiment showed that the optimal resolution of super-resolved microbubble imaging for brain microvascular imaging can reach micron level,and the imaging depth exceeds 35 mm.Conclusion: Super-resolution imaging technology can achieve high-resolution,fast calculation monitoring imaging of microbubbles during tissue damage.The high-altitude time-resolved imaging method will also become the basis of the subsequent microbubble imaging research for our further study,and also provide an important experimental basis for the clinical application of non-invasive transcranial ultrasound. |
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