采用動(dòng)態(tài)電阻抗成像技術(shù)對(duì)腦損傷動(dòng)物模型監(jiān)測(cè)的實(shí)驗(yàn)研究
發(fā)布時(shí)間：2018-08-21 13:50
【摘要】：腦損傷（Brain Injury, BI）具有病情兇險(xiǎn)、死亡率高的特點(diǎn)，是急性腦病中最嚴(yán)重的一種，預(yù)后較差，是人類致死性疾病之一[1]。目前臨床尚無(wú)法實(shí)現(xiàn)腦損傷的早期檢測(cè)與實(shí)時(shí)監(jiān)測(cè)，腦損傷不能得到及時(shí)干預(yù)和治療是導(dǎo)致預(yù)后差的主要原因[2]。腦損傷主要的輔助診斷技術(shù)包括X射線、CT、MRI、超聲波檢查、腦血管造影、顱內(nèi)壓監(jiān)測(cè)（ICP）、脊髓穿刺等，這些方法雖能獲得一些有價(jià)值的診斷信息，但都無(wú)法進(jìn)行腦損傷的實(shí)時(shí)動(dòng)態(tài)監(jiān)測(cè)并在第一時(shí)間預(yù)警，致使患者錯(cuò)過(guò)最佳的治療時(shí)間窗，臨床中因腦損傷引起的致死、致殘時(shí)有發(fā)生，因而迫切需要一種有效方法實(shí)現(xiàn)對(duì)腦損傷的實(shí)時(shí)動(dòng)態(tài)監(jiān)測(cè)。 電阻抗斷層成像(Electrical Impedance Tomography, EIT)是一種以人體內(nèi)部電阻(電導(dǎo))率的分布為成像目標(biāo)的醫(yī)學(xué)成像技術(shù)[3]。其主要思想是通過(guò)對(duì)測(cè)量目標(biāo)外加驅(qū)動(dòng)信號(hào)（驅(qū)動(dòng)電壓或電流）并測(cè)量其邊界電壓或電流分布，通過(guò)對(duì)偏微分方程的逆問(wèn)題進(jìn)行求解，近似計(jì)算出目標(biāo)區(qū)域內(nèi)的電導(dǎo)率分布。這一新技術(shù)具有無(wú)創(chuàng)傷、功能成像、成本低廉、體積小、操作簡(jiǎn)單、動(dòng)態(tài)實(shí)時(shí)監(jiān)護(hù)等優(yōu)點(diǎn)，在腦損傷的床旁動(dòng)態(tài)圖像監(jiān)測(cè)應(yīng)用上具有廣闊的應(yīng)用前景和研究?jī)r(jià)值。 我們課題組經(jīng)過(guò)近二十年的研究，在電阻抗成像的硬件采集系統(tǒng)和成像算法以及動(dòng)物、臨床實(shí)驗(yàn)等方面取得了突破性的進(jìn)展，在顱腦動(dòng)態(tài)圖像監(jiān)護(hù)領(lǐng)域更是達(dá)到國(guó)際水平。在此基礎(chǔ)上，為進(jìn)一步推進(jìn)EIT的臨床應(yīng)用，針對(duì)腦損傷電阻抗動(dòng)態(tài)圖像監(jiān)護(hù)研究中的實(shí)際問(wèn)題，本文主要從以下兩個(gè)方面開展研究： (1)腦水腫動(dòng)物模型電阻抗動(dòng)態(tài)圖像監(jiān)護(hù)的實(shí)驗(yàn)研究 為使研究更貼近于臨床，改進(jìn)了實(shí)驗(yàn)電極。前期的動(dòng)物實(shí)驗(yàn)將實(shí)驗(yàn)電極嵌入顱骨內(nèi)，此種方法雖然有效地降低了電極系統(tǒng)的接觸阻抗，但是容易引起出血并且破壞顱內(nèi)壓環(huán)境而影響實(shí)驗(yàn)結(jié)果。因此，為使電極系統(tǒng)滿足實(shí)驗(yàn)要求，在前期實(shí)驗(yàn)電極的基礎(chǔ)上改進(jìn)了電極系統(tǒng)，其構(gòu)成包括絕緣板、外部牽引系統(tǒng)和設(shè)置在絕緣板上的電極探頭。該電極探頭可自由調(diào)節(jié)長(zhǎng)度，并通過(guò)下拉部件使其方便且嚴(yán)密的接觸于實(shí)驗(yàn)動(dòng)物顱骨頂部。利用兩電極法對(duì)改進(jìn)后的實(shí)驗(yàn)電極與EIT臨床實(shí)驗(yàn)中Ag/AgCl電極的性能進(jìn)行對(duì)比。 放射腦水腫動(dòng)物模型的制備采用單次大劑量Dt30Gy，劑量率300cGy/min，利用CADPLAN/HELIOS三維治療計(jì)劃系統(tǒng)嚴(yán)格按照實(shí)驗(yàn)要求設(shè)計(jì)放療計(jì)劃。并利用電阻抗成像系統(tǒng)對(duì)動(dòng)物模型進(jìn)行監(jiān)測(cè)，觀察和分析隨著時(shí)間的改變放射損傷性腦水腫在EIT圖像中的變化。之后再利用解剖學(xué)方法、影像學(xué)方法、病理學(xué)方法等對(duì)模型和結(jié)果進(jìn)行驗(yàn)證。 本研究采用高能X線，構(gòu)造了三維準(zhǔn)確定位的放射損傷腦水腫動(dòng)物模型，該模型具有以下優(yōu)點(diǎn)：準(zhǔn)確定位；閉合性；水腫范圍可控；更好的模擬臨床。因此我們提出利用放射損傷的方法制造腦水腫動(dòng)物模型，并首次開展了采用EIT技術(shù)對(duì)此種腦水腫動(dòng)物模型進(jìn)行檢測(cè)的實(shí)驗(yàn)研究。 (2)內(nèi)源性腦出血?jiǎng)游锬Ｐ碗娮杩箘?dòng)態(tài)圖像監(jiān)護(hù)的實(shí)驗(yàn)研究 利用膠原蛋白酶誘導(dǎo)法建立腦出血?jiǎng)游锬Ｐ�，選擇紋狀體部位注射膠原蛋白酶制造腦實(shí)質(zhì)出血模型，簡(jiǎn)要實(shí)驗(yàn)過(guò)程包括，麻醉、脫毛、鉆孔、注射膠原酶和模型驗(yàn)證等。其優(yōu)勢(shì)在于此種模型可以根據(jù)膠原蛋白酶濃度和量的調(diào)節(jié)控制出血量和范圍，出血具有延遲性，可以用EIT方法監(jiān)測(cè)整個(gè)出血過(guò)程，并且注射微量膠原蛋白酶，不形成自身藥物在顱內(nèi)的占位效應(yīng)，更接近于實(shí)際腦出血，更為重要的是采用此模型可以封閉注射孔，保證腦出血過(guò)程中顱內(nèi)壓的存在，更好的模擬臨床中腦出血的情況，利用電阻抗成像系統(tǒng)對(duì)動(dòng)物模型進(jìn)行監(jiān)測(cè)，觀察和分析隨著時(shí)間的改變放射損傷性腦水腫在EIT圖像中的變化。 研究結(jié)果表明： (1)利用電阻抗成像技術(shù)監(jiān)測(cè)放射損傷性腦水腫早期的電阻抗改變，發(fā)現(xiàn)EIT局部重構(gòu)均值和動(dòng)態(tài)圖像時(shí)間序列發(fā)生明顯改變，實(shí)驗(yàn)組MLRV每小時(shí)變化量為（0.003529±0.00089），與對(duì)照組(3.1±1.2)E-5有顯著性差異(P0.05)，阻抗明顯升高，位置和造模的位置基本吻合。通過(guò)影像學(xué)、病理學(xué)和解剖學(xué)檢測(cè)，我們發(fā)現(xiàn)，組織切片在照射12小時(shí)后不能從解剖學(xué)上發(fā)現(xiàn)放射性腦水腫，利用CT在腦組織照射三天很難發(fā)現(xiàn)放射損傷性腦水腫，在光學(xué)顯微鏡下發(fā)現(xiàn)照射后24小時(shí)細(xì)胞發(fā)生水腫和損傷，電鏡檢測(cè)結(jié)果顯示照射后10小時(shí)能夠檢測(cè)放射損傷性腦水腫。初步實(shí)驗(yàn)結(jié)果表明：利用電阻抗方法可檢測(cè)到處于急性期內(nèi)的腦放射損傷即放射性腦水腫，證明了EIT在檢測(cè)腦水腫的敏感性和可行性。 (2)利用電阻抗成像技術(shù)監(jiān)測(cè)動(dòng)物腦出血早期電阻抗改變，通過(guò)EIT一維信息重構(gòu)幅值最大值和二維動(dòng)態(tài)圖像時(shí)間序列的變化，AM每分鐘變化量為0.012±0.0075，與對(duì)照組有顯著性差異(P0.05)，解剖學(xué)切片、病理學(xué)、影像學(xué)、及阻抗分析儀檢測(cè)結(jié)果，發(fā)現(xiàn)：隨著時(shí)間的延長(zhǎng)、血腫的加劇和范圍的擴(kuò)大，其腦部阻抗值升高。初步實(shí)驗(yàn)結(jié)果表明：目標(biāo)區(qū)域的電阻抗變化是由腦出血引起，EIT可監(jiān)測(cè)到這種變化；結(jié)合CT掃描結(jié)果，說(shuō)明腦出血早期組織的阻抗改變可能早于密度變化，EIT有可能成為比影像學(xué)更敏感的檢測(cè)手段。 本研究旨在為腦損傷的早期診斷提供一種實(shí)時(shí)、動(dòng)態(tài)、無(wú)創(chuàng)的監(jiān)測(cè)方法，，通過(guò)動(dòng)物實(shí)驗(yàn)驗(yàn)證了EIT成像技術(shù)對(duì)腦損傷監(jiān)測(cè)的可行性和敏感性，證明了EIT具備腦損傷早期檢測(cè)的應(yīng)用前景，對(duì)EIT的臨床應(yīng)用具有深遠(yuǎn)影響。
[Abstract]:Brain Injury (BI) is one of the most serious acute encephalopathy with poor prognosis and is one of the fatal diseases of human beings. The main auxiliary diagnostic techniques for brain injury include X-ray, CT, MRI, ultrasonic examination, cerebral angiography, intracranial pressure monitoring (ICP), spinal cord puncture and so on. Although these methods can obtain some valuable diagnostic information, they can not real-time dynamic monitoring of brain injury and early warning at the first time, resulting in patients missing the best treatment window. In clinic, death and disability caused by brain injury occur frequently, so an effective method is urgently needed to realize real-time dynamic monitoring of brain injury.
Electrical Impedance Tomography (EIT) is a medical imaging technique that targets the distribution of electrical resistance (conductivity) in the body [3]. This new technique has many advantages, such as non-invasive, functional imaging, low cost, small size, simple operation, dynamic real-time monitoring and so on. It has broad application prospects and research value in the application of bedside dynamic image monitoring of brain injury.
After nearly 20 years of research, our research group has made breakthroughs in hardware acquisition system, imaging algorithm, animal and clinical experiments of EIT, and has reached the international level in the field of brain dynamic image monitoring. The practical problems in image monitoring research are studied in the following two aspects:
(1) experimental study of electrical impedance monitoring in animal models of cerebral edema
In order to make the study closer to the clinic and improve the experimental electrode, the experimental electrode was embedded in the skull in the previous animal experiment. Although this method effectively reduces the contact impedance of the electrode system, it is easy to cause bleeding and destroy the intracranial pressure environment and affects the experimental results. The electrode system is improved on the basis of the electrode test, which consists of an insulating plate, an external traction system and an electrode probe mounted on the insulating plate. The electrode probe can be freely adjusted in length and can be conveniently and tightly contacted on the top of the skull of experimental animals by pulling down the parts. The improved electrode and EIT are clinically applied by two-electrode method. The performance of Ag/AgCl electrode was compared in the experiment.
The animal model of radiation brain edema was prepared with a single high dose of Dt30Gy and a dose rate of 300cGy/min. The radiotherapy plan was designed strictly according to the experimental requirements by using CADPLAN/HELIOS three-dimensional treatment planning system. The animal model was monitored by electrical impedance imaging system, and the EIT images of radiation-induced brain edema were observed and analyzed with time. Then the model and results were validated by anatomy, imaging and pathology.
In this study, we used high-energy X-ray to construct an animal model of radiation-induced brain edema, which has the following advantages: accurate localization; closure; controlled edema range; better clinical simulation. The experimental study of animal models of cerebral edema.
(2) experimental study on dynamic image monitoring of electrical impedance in animal models of intracerebral hemorrhage
Intracerebral hemorrhage animal model was established by collagenase-induced method, and the striatum was injected with collagenase to make the model of cerebral parenchymal hemorrhage. The brief experimental process included anesthesia, depilation, drilling, injection of collagenase and model validation. And the hemorrhage is delayed. EIT method can be used to monitor the whole hemorrhage process, and injection of micro-collagenase, not forming their own drug occupying effect in the brain, more close to the actual cerebral hemorrhage, more importantly, the use of this model can close the injection hole, ensure the existence of intracranial pressure in the process of cerebral hemorrhage, better simulation of impending. In order to observe and analyze the changes of brain edema caused by radiation injury in EIT images with the change of time, electrical impedance tomography (EIT) was used to monitor the animal model of cerebral hemorrhage in bed.
The results show that:
(1) Electrical impedance changes in the early stage of radiation-induced brain edema were monitored by electrical impedance tomography (EIT). It was found that the mean value of local EIT reconstruction and the time series of dynamic images changed significantly. The hourly variation of MLRV in the experimental group was (0.003529 [0.00089], which was significantly different from that in the control group (3.1 [1.2] E-5) (P 0.05). Impedance increased significantly, location and modeling. By imaging, pathological and anatomical examination, we found that the tissue slices could not find radioactive brain edema from anatomy 12 hours after irradiation. It was difficult to find radiation-induced brain edema by CT in three days after irradiation, and the cells were found to have edema and injury 24 hours after irradiation under optical microscope. The results of electron microscopy showed that the brain edema could be detected 10 hours after irradiation. The preliminary results showed that the brain edema in acute stage could be detected by electrical impedance method, which proved the sensitivity and feasibility of EIT in detecting brain edema.
(2) Electrical impedance tomography (EIT) was used to monitor the changes of electrical impedance in the early stage of cerebral hemorrhage. The maximum amplitude and the time series of two-dimensional dynamic images were reconstructed by one-dimensional EIT information. The change of AM per minute was 0.012 (+ 0.0075), which was significantly different from that of the control group (P 0.05). Preliminary results showed that the electrical impedance changes in the target area were caused by cerebral hemorrhage and could be monitored by EIT. Combined with CT scan results, the impedance changes in early cerebral hemorrhage tissues may be earlier than the density changes, and EIT may be possible. It can become a more sensitive detection method than imaging.
The purpose of this study is to provide a real-time, dynamic and non-invasive monitoring method for the early diagnosis of brain injury. The feasibility and sensitivity of EIT imaging technology for monitoring brain injury are verified by animal experiments. It is proved that EIT has the application prospect of early detection of brain injury and has a profound impact on the clinical application of EIT.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R-332
本文編號(hào)：2195932
[Abstract]:Brain Injury (BI) is one of the most serious acute encephalopathy with poor prognosis and is one of the fatal diseases of human beings. The main auxiliary diagnostic techniques for brain injury include X-ray, CT, MRI, ultrasonic examination, cerebral angiography, intracranial pressure monitoring (ICP), spinal cord puncture and so on. Although these methods can obtain some valuable diagnostic information, they can not real-time dynamic monitoring of brain injury and early warning at the first time, resulting in patients missing the best treatment window. In clinic, death and disability caused by brain injury occur frequently, so an effective method is urgently needed to realize real-time dynamic monitoring of brain injury.
Electrical Impedance Tomography (EIT) is a medical imaging technique that targets the distribution of electrical resistance (conductivity) in the body [3]. This new technique has many advantages, such as non-invasive, functional imaging, low cost, small size, simple operation, dynamic real-time monitoring and so on. It has broad application prospects and research value in the application of bedside dynamic image monitoring of brain injury.
After nearly 20 years of research, our research group has made breakthroughs in hardware acquisition system, imaging algorithm, animal and clinical experiments of EIT, and has reached the international level in the field of brain dynamic image monitoring. The practical problems in image monitoring research are studied in the following two aspects:
(1) experimental study of electrical impedance monitoring in animal models of cerebral edema
In order to make the study closer to the clinic and improve the experimental electrode, the experimental electrode was embedded in the skull in the previous animal experiment. Although this method effectively reduces the contact impedance of the electrode system, it is easy to cause bleeding and destroy the intracranial pressure environment and affects the experimental results. The electrode system is improved on the basis of the electrode test, which consists of an insulating plate, an external traction system and an electrode probe mounted on the insulating plate. The electrode probe can be freely adjusted in length and can be conveniently and tightly contacted on the top of the skull of experimental animals by pulling down the parts. The improved electrode and EIT are clinically applied by two-electrode method. The performance of Ag/AgCl electrode was compared in the experiment.
The animal model of radiation brain edema was prepared with a single high dose of Dt30Gy and a dose rate of 300cGy/min. The radiotherapy plan was designed strictly according to the experimental requirements by using CADPLAN/HELIOS three-dimensional treatment planning system. The animal model was monitored by electrical impedance imaging system, and the EIT images of radiation-induced brain edema were observed and analyzed with time. Then the model and results were validated by anatomy, imaging and pathology.
In this study, we used high-energy X-ray to construct an animal model of radiation-induced brain edema, which has the following advantages: accurate localization; closure; controlled edema range; better clinical simulation. The experimental study of animal models of cerebral edema.
(2) experimental study on dynamic image monitoring of electrical impedance in animal models of intracerebral hemorrhage
Intracerebral hemorrhage animal model was established by collagenase-induced method, and the striatum was injected with collagenase to make the model of cerebral parenchymal hemorrhage. The brief experimental process included anesthesia, depilation, drilling, injection of collagenase and model validation. And the hemorrhage is delayed. EIT method can be used to monitor the whole hemorrhage process, and injection of micro-collagenase, not forming their own drug occupying effect in the brain, more close to the actual cerebral hemorrhage, more importantly, the use of this model can close the injection hole, ensure the existence of intracranial pressure in the process of cerebral hemorrhage, better simulation of impending. In order to observe and analyze the changes of brain edema caused by radiation injury in EIT images with the change of time, electrical impedance tomography (EIT) was used to monitor the animal model of cerebral hemorrhage in bed.
The results show that:
(1) Electrical impedance changes in the early stage of radiation-induced brain edema were monitored by electrical impedance tomography (EIT). It was found that the mean value of local EIT reconstruction and the time series of dynamic images changed significantly. The hourly variation of MLRV in the experimental group was (0.003529 [0.00089], which was significantly different from that in the control group (3.1 [1.2] E-5) (P 0.05). Impedance increased significantly, location and modeling. By imaging, pathological and anatomical examination, we found that the tissue slices could not find radioactive brain edema from anatomy 12 hours after irradiation. It was difficult to find radiation-induced brain edema by CT in three days after irradiation, and the cells were found to have edema and injury 24 hours after irradiation under optical microscope. The results of electron microscopy showed that the brain edema could be detected 10 hours after irradiation. The preliminary results showed that the brain edema in acute stage could be detected by electrical impedance method, which proved the sensitivity and feasibility of EIT in detecting brain edema.
(2) Electrical impedance tomography (EIT) was used to monitor the changes of electrical impedance in the early stage of cerebral hemorrhage. The maximum amplitude and the time series of two-dimensional dynamic images were reconstructed by one-dimensional EIT information. The change of AM per minute was 0.012 (+ 0.0075), which was significantly different from that of the control group (P 0.05). Preliminary results showed that the electrical impedance changes in the target area were caused by cerebral hemorrhage and could be monitored by EIT. Combined with CT scan results, the impedance changes in early cerebral hemorrhage tissues may be earlier than the density changes, and EIT may be possible. It can become a more sensitive detection method than imaging.
The purpose of this study is to provide a real-time, dynamic and non-invasive monitoring method for the early diagnosis of brain injury. The feasibility and sensitivity of EIT imaging technology for monitoring brain injury are verified by animal experiments. It is proved that EIT has the application prospect of early detection of brain injury and has a profound impact on the clinical application of EIT.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R-332
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