基于多光谱光学内源信号成像的皮层扩散性抑制过程多参数监测

发布时间：2018-05-14 05:11

本文选题：皮层扩散性抑制 + 血红蛋白　；参考：《华中科技大学》2013年博士论文

【摘要】：皮层扩散性抑制(Cortical spreading depression, CSD)作为偏头痛、脑缺血以及脑外伤等多种神经性疾病的病理学模型,对其在体发展特性的研究和了解,特别是对其引起的血液动力学响应和能量代谢变化的研究可以帮助人们更好的研究和治疗这些神经性疾病。多光谱光学内源信号(Optical intrinsic signal, OIS)成像技术不仅具有较高的时间和空间分辨率,并且通过一定的数据分析处理后还可以提供多参数信息(血液动力学、线粒体代谢以及光散射)。因此,我们利用多光谱光学内源信号成像技术来实现对活体动物(大鼠和小鼠)CSD发展过程的多参数监测。主要研究内容如下： (1)首先介绍了多光谱OIS成像系统,并推导了多光谱OIS的基本数据分析模型——修正的朗伯比尔定律,针对以前多光谱OIS数据分析过程中相关因素考虑不全面的问题,分析了一系列与脑组织光吸收有关的生色团(血红蛋白,水,细胞色素c,细胞色素氧化酶,NADH和FAD),给出了这些生色团可见光范围内的吸收光谱,并确定其是否参与多光谱OIS的数据分析,从而最终推导出多光谱OIS的数据分析公式,为准确分析CSD相关的多光谱OIS提供方法学基础。我们还模拟和分析了数据分析模型中的重要参数——差分路径因子,定性的给出了差分路径因子随组织吸收、散射特性改变所产生的变化特征,并估计了脑组织的吸收和散射等光学特性,最后给出了可见光范围内(450-650nm)差分路径因子随波长的变化曲线。 (2)采用多光谱OIS成像同时监测了大鼠CSD过程中多生理参数的变化,包括氧合血红蛋白(Oxygen-hemoglobin, HbO)、脱氧血红蛋白(Deoxygen-hemoglobin，，HbR)、细胞色素c、细胞色素氧化酶、FAD以及光散射。发现CSD过程中450,470,500,530,550,570nm OIS显示出四相变化,而600,630和650nm OIS表现出复杂的两相变化。而在CSD过程中,HbO显示出显著的上升;HbR则出现下降、上升、下降的三相变化；光散射显示了先增强后减弱的变化特征；细胞色素c和细胞色素氧化酶先是被还原接着又被氧化；而FAD下降然后恢复至基线值。其中HbR的上升,细胞色素c和细胞色素氧化酶的还原说明了大鼠CSD过程中氧的供应曾一度存在不足。发现在多光谱数据拟合过程中如果不考虑其它生色团(FAD,细胞色素c和细胞色素氧化酶)和散射的变化,得到的血红蛋白浓度变化(HbO和HbR)很可能不准确。并且CSD过程中细胞色素c的变化和550nm OIS紧密相关；细胞色素氧化酶的变化和450,600,650nm OIS紧密相关；而FAD的变化和450,470nm OIS紧密相关。所以在使用这些波长的OIS计算血红蛋白变化时,应当考虑这些生色团的影响,从而避免HbO和HbR计算的不准确。 (3)采用多光谱光学内源信号成像系统研究了小鼠CSD的时变特性。30分钟内在小鼠脑皮层分别诱发两次CSD,发现这两次CSD显示出不同特性：450,470,500,530,550和570nm OIS在第一次CSD中显示出三相变化,最后幅值高于基线水平,而在第二次CSD中为四相变化；600,630和650nm OIS在第一次CSD中具有四相变化,并且最后幅值保持在低于基线值水平,600nm OIS在第二次CSD中仍具有四相变化,而630和650nm OIS在第二次CSD中只有三相变化,并且最后都能恢复到本次CSD发生之前的基线水平；HbO和总血红蛋白(Total hemoglobin, HbT)在第一次CSD中是下降的,但在第二次CSD中是上升的；光散射在第一次CSD中先上升然后下降最后长时间缓慢下降,但在第二次CSD中只有上升和恢复的变化；脑皮层大动脉管径在第一次CSD中有三相变化：剧烈收缩,恢复以及缓慢收缩,在第二次CSD中有四相变化：小舒张,收缩,大舒张以及恢复。而两次CSD中还原态细胞色素c和细胞色素氧化酶的上升以及FAD的下降都说明线粒体是处于还原状态,脑组织是处于缺氧的状态,只是第一次CSD的缺氧状况相较于第二次CSD更为严重。另外,第一次CSD会引起脑皮层很长时间的严重缺血,表现为HbT一直缓慢地下降,动脉血管也缓慢而长时间地收缩。 (4)研究了小鼠单侧颈总动脉结扎缺血后诱发的连续两次CSD的发展特性,以及双侧颈总动脉结扎缺血后小鼠自发CSD的发展特性。发现单侧缺血小鼠第一次CSD各生理参数的变化大体上和未缺血情况类似,只是持续时间明显变长,而还原态细胞色素c和细胞色素氧化酶响应幅度变大；单侧缺血小鼠第二次CSD多数生理参数的变化大体上也和未缺血情况类似,只有HbO显示出不一致,未缺血情况下Hb0是急剧上升的,而缺血状态下HbO有一个初始的小下降,然后小幅上升。小鼠双侧颈总动脉结扎缺血后自发CSD的多光谱OIS表现为所有波长统一的光强上升,而这种上升是由于散射增强而导致的。
[Abstract]:Cortical spreading depression (CSD) is a pathological model of multiple neuropathic diseases such as migraine, cerebral ischemia and brain injury. The research and understanding of its development characteristics, especially the study of hemodynamic response and energy metabolism, can help people to better study and treat it. The Optical intrinsic signal (OIS) imaging technology not only has high time and spatial resolution, but also provides multi parameter information (hemodynamics, mitochondrial thanks and light scattering) after a certain data analysis. Therefore, we use multispectral optical interior. Source signal imaging technology is used to monitor the development of CSD in living animals (rats and mice). The main contents are as follows:
(1) firstly, the multi spectral OIS imaging system is introduced, and the basic data analysis model of multi spectral OIS, the modified Longbow Bill's law, is derived. In view of the problems related to the previous multi spectral OIS data analysis, a series of chromophores (hemoglobin, water and cytochrome c) related to the optical absorption of brain tissue are analyzed. Cytochrome oxidase, NADH and FAD), give the absorption spectrum in the visible light range of these chromophores, and determine whether it participates in the data analysis of multi spectral OIS, and finally deduces the data analysis formula of multi spectral OIS, which is the basis for accurate analysis of CSD related multi spectral OIS basis. We also simulated and analyzed data analysis. The important parameter in the model, the difference path factor, qualitatively gives the variation characteristics of the difference path factor with the absorption and scattering characteristics, and estimates the optical properties of the absorption and scattering of the brain tissue. Finally, the variation curve of the 450-650nm difference path factor in the visible light range with the wavelength is given.
(2) multispectral OIS imaging was used to monitor the changes of multiple physiological parameters in CSD process in rats, including Oxygen-hemoglobin (HbO), deoxy hemoglobin (Deoxygen-hemoglobin, HbR), cytochrome c, cytochrome oxidase, FAD, and light scattering. The 450470500530550570nm OIS showed a four phase transition in the CSD process. In addition, 600630 and 650nm OIS showed complex two phase changes. In the CSD process, HbO showed a significant rise; HbR decreased, increased, and dropped three phase changes; light scattering showed a first enhanced and then weakened change; cytochrome c and cytochrome oxidase were first reduced and then oxidized; and FAD decreased then then. The rise of HbR, the reduction of cytochrome c and cytochrome oxidase showed that the oxygen supply in the rat CSD process was once insufficient. It was found that the hemoglobin obtained in the multispectral data fitting process was not considered if the other chromophores (FAD, cytochrome c and cytochrome oxidase) and scattering changes were not taken into consideration. Concentration changes (HbO and HbR) are likely to be inaccurate. And the changes in cytochrome C in CSD are closely related to 550nm OIS; the changes in cytochrome oxidase are closely related to 450600650nm OIS; and the change of FAD is closely related to 450470nm OIS. So these should be considered when using these wavelengths to calculate the changes in hemoglobin. The influence of chromophores is thus avoided to avoid inaccuracies in HbO and HbR calculations.
(3) using the multi spectral optical internal source signal imaging system to study the time-varying characteristic of mouse CSD in.30 minutes, the mouse cerebral cortex was induced two times CSD respectively. It was found that the two CSD showed different characteristics: 450470500530550 and 570nm OIS showed a three phase change in the first CSD, and the last amplitude was higher than the baseline level, but in the second CSD. For the four phase change; 600630 and 650nm OIS have four phase changes in the first CSD, and the final amplitude is kept below the baseline level. 600nm OIS still has a four phase change in the second CSD, while 630 and 650nm OIS have only three phase changes in second CSD, and finally all can be restored to the baseline level before this CSD; HbO and The total hemoglobin (Total hemoglobin, HbT) was reduced in the first CSD, but increased in the second CSD; light scattering first rose in the first CSD and dropped for the last long slow decline, but in the second CSD there was only a rise and recovery; the diameter of the cerebral cortex was three phase change in the first CSD: play Severe contraction, recovery and slow contraction, four phase changes in the second CSD: small diastolic, contraction, diastolic and recovery. While the reduction of cytochrome c and cytochrome oxidase in the two CSD and the decline of FAD both indicate that the mitochondria are in the state of reduction, the brain group is in a state of hypoxia, but the first CSD anoxia. The condition is more serious than the second CSD. In addition, the first CSD causes severe ischemia of the cerebral cortex for a long time, showing that HbT has been slow down, and the arteries of the arteries also shrink slowly and long.
(4) the development characteristics of continuous two CSD induced by unilateral carotid artery ligation and ischemia in mice and the development characteristics of spontaneous CSD after ligating the bilateral common carotid artery in mice were studied. It was found that the changes of the first CSD physiological parameters of the unilateral ischemic mice were similar to those of the non ischemic condition, but the duration was obviously longer, and the reduction state was reduced. The response amplitude of cytochrome c and cytochrome oxidase increased. The changes of most physiological parameters of second times CSD in unilateral ischemic mice were similar to that of non ischemia in general. Only HbO showed disagreement and Hb0 increased sharply in the absence of ischemia, while HbO had a small initial decrease in ischemic state and then slightly increased. The multispectral OIS of spontaneous CSD after the ligation of the common carotid artery is a uniform light intensity rising at all wavelengths, and this increase is due to the enhancement of scattering.

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R310

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