生物电阻抗断层成像系统在猪脑内血肿模型急性期实时监护的初步研究
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摘要
背景和目的
脑血管意外分为出血性脑血管病和缺血性脑血管病,是危害人类健康的最严重的杀手之一。每年因为脑血管意外引起的死亡人数在人类死亡原因中位列第三位,同时它也是致残率最高的疾病之一。早期诊断和早期治疗是降低脑血管意外致死率和致残率最好的办法,随着医学辅助技术的发展,尤其是CT和MRI的问世,大大解决了脑血管意外的早期诊断问题,也使得治疗取得了长足的进步。以往的观点认为脑出血,尤其是高血压脑出血的出血过程是单时像过程,很快就会停止,但是越来越多的证据表明血肿的进行性扩大以及再次出血的情况并不少见,这样临床症状的观察以及反复的辅助检查就成为脑出血患者进展期的唯一手段。但是由于现有的影像学检查办法如CT、MRI、TCD等仅仅能显示一个固定的时间点的颅内资料,无法提供一个连续的影像学资料,在两次复查CT之间只能通过医生观察临床症状和生命体征来判断病情有无变化,因此临床上迫切需要一种能够实时提供颅内血肿变化的监护系统。生物电阻抗是生物体的基本属性之一,电阻抗断层成像系统可以提供生物体电阻抗的变化情况。由于电阻抗断层成像技术具有无创无害、成本低廉、操作简便、功能成像等优点,适于进行长时间的图像监护。本实验在猪脑出血模型中应用生物电阻抗断层成像系统实时监护脑出血后猪脑内电阻抗变化状况,旨在提出一种能够实时观察颅内变化的新的监护系统。
材料与方法
物理模型试验采用一个半球形容器内放置一个用以模拟颅骨的内石膏壳构成。在球壳内注入饱和CaSO4溶液模拟脑组织和头皮。在半球形容器的内侧壁以等间隔的方式安放16个电极,用与血液电阻率一致的琼脂块来模拟血液在石膏壳模拟的颅腔内移动,观察EIT系统对血液信号的敏感性。
实验动物采用体重15公斤左右的小猪28只,雌雄不限,术前12小时禁食,4小时禁水。其中打开颅骨状态下注射自体不抗凝动脉血4只,注射生理盐水组8只,注射蒸馏水组8只,保持颅腔完整性注血组8只。采用速眠新和3%戊巴比妥钠复合麻醉,术中给于维持量的戊巴比妥(10mg/kg·h),采用自体血注入的猪额叶脑出血模型。以双眼内龇连线为基准线,层距2mm行CT冠状扫描。根据CT扫描结果,选取双眼外眦连线旁正中1cm处为穿刺点并用颅钻钻孔。取股动脉血10ml,沿钻好的穿刺孔穿刺,进针2cm,用微量泵以40ul/s的速度将5ml动脉血(生理盐水或蒸馏水)在3分钟内注入猪脑。1小时后行CT复查,并计算血肿量。
EIT测量采用16导联测量法,以猪头最长横径和前后径分别为长短径形成一个圆形的近似颅脑外界,将16个电极等间隔放置。注血前后实时连续监测至少30分钟。
手术结束后将动物深度麻醉处死,完整取脑组织行大体观察。手术过程采用无菌术,手术过程用恒温毯保持动物体温在38.5度。
结果:
1物理模型结果提示模拟血液的琼脂块由“颅腔”内移动过程中,成像结果能相对较好地反映模型中出血区域的大小及位置。
2所有动物造模均成功,出血模型血肿位置位于右侧额叶皮质下,大小为4.88±0.12ml。CT检查显示血肿形成,大体标本提示血肿形成,符合脑出血急性期病理改变。注蒸馏水及生理盐水模型大体可见注水针道位于脑额叶白质内。
3 EIT结果背景期图像显示脑EIT值均一。去除颅骨注血组注血开始后,在注血区域可见明显的电阻抗值降低区域,注血停止后,电阻抗值缓慢回升。注射生理盐水组注射开始后,可见明显的信号降低区域,随注水量的增加逐渐降低,随后电阻抗维持一段时间的逐渐回升,注射蒸馏水组注射开始后,可见明显的信号升高区域,随注水量的增加逐渐升高,维持一段时间后逐渐回落;闭合式注血组注血开始后,在注血区域可见明显的电阻抗值升高区域,注血停止后,电阻抗缓慢下降;
结论
通过物理模型实验,发现EIT成像结果能相对较好地反映模型中出血区域的大小及位置。通过对去除颅骨后猪颅内注入非抗凝血模型的EIT监护研究,发现随着出血量的不断增加,出血灶区域的阻抗断层图像显示阻抗值逐渐降低。通过对猪颅内注入生理盐水、蒸馏水实验说明EIT图像能灵敏地反映猪颅内阻抗降低和升高的变化。通过闭合式猪颅内注入非抗凝血模型的建立及EIT监护实验图像的变化,提示颅内出血与颅内压的变化有显著相关、颅内压的变化及其代偿机制客观存在脑出血后颅内压变化的动态过程需要研究。
Background and objective
Stroke includes two types: intracranial hemorrhage and brain infarction. It is one of the grisly killers of the people’s health. And it is one of the most common and dangerous disease with very high mortality & disability rate in alive people. Early detection and diagnosis are the keys to increase the survival rate and decrease the complications of the intracranial hemorrhage (ICH). Following the development of medical imageology, especially the CT and MRI application, early diagnosis became easy and facility and strength assist the earlier treatment. Former viewpoint about the intracranial hemorrhage deemed that the process of the brain hemorrhage was a single vector course, and would stop quickly. But the newer viewpoint considered that this process might be a incessancy process or appear repeated, and those was be approved during the clinical experience. Therefore the repeated clinical symptom observed and assistants examined are obligatory. However, nowadays imaging facility (CT, MRI, TCD et al) only offers incontinuous data, and can not persistent offer the correlative data. During the period of former and latter CT scans, surgeons obtain the accurate clinical data only through the clinical syndromes and heart electricity and breath monitor system. It brings much inconvenient and might affect the treatment in time. Consequently it pressed for a new monitor system that could supply the hemorrhage process in real time in clinical.
Electrical bio-impedance is one of the instinctual properties of the organism. Electrical Impedance Tomography (EIT) can provide the variety of the electrical impedance during the pathological process. For EIT technique has the advantages of harmless,low cost, easy to use and functional imaging. Those features make it more fit for long time imaging monitoring. Therefore, in this study, we arrange to image monitoring the intracranial hemorrhage animal model use EIT technique. And try to obtain a new system for monitoring the skull’s impedance variation.
Material and method
We place a plaster hemispherical shell into a hemispherical container to simulate the skull layer and filling the container with CaSO4 saturated solution to simulate the scalp and the brain tissues. The resistivity disturbance was made by immersed an agar to simulate the disturbance caused by blood. In animal model experiment, we use animal model with the instrument of EIT to study the resistance changes of the brain in acute ICH. 28 piglets (weight 15 kg) were were deprived of food and water overnight before the experimental procedure. And all the animal were divided into four groups, one group including 4 animals infusing artery blood deprived the skull and scalp;the others group including 8 animals in each one: the second group infusing artery blood, the control groups infusing distilled water and saline separately. After anesthetized successes, a cranial burr hole (1.5 mm) was then drilled 10 mm to the right of the sagittal and 10 mm anterior to the coronal suture. A 7.5-gauge sterile plastic trocar (length 19 mm) was then placed stereotaxically into the center of the frontal cerebral white matter at the level of the caudate nucleus and cemented in place. An infusion pump was then connected, and 5 ml of blood (distilled water or saline) was infused into the brain tissue at a rate of 40μl per second within 3 minutes.
16 Ag/AgCl electrodes were placed on the scalp of piglets annularly. The centre of a circle was located on the cross of the joining line of two lateral-canthi and the median line of the head. The semidiameter of the circle was 7-8cm. All of the electrodes were located on the circumference orderly. Before the blood infusing, we monitored the foreground at least for 60 frames. After the blood infusion was finished, we continuously collected the data for at least 30 minutes. After EIT monitor finished, we had an X-ray CT (GE Company) scan to validate the model. At the same time, the volume of the hematoma was calculated according to the CT imaging. All surgical procedures were performed with the use of aseptic techniques. Core temperature was measured with a rectal thermistor probe and was maintained at 38.5±0.5°C with the use of a warm water blanket.
Result
The results in physical model show that the skull handicapped the detection of resistivity disturbance inside cranial greatly. And in animal model expericment, in the group of infusing blood with deprived the skull and scalp, the resisitivity decreased rapidly, and after the stopping the infusing the resistivity increased slowly; in the distilled water, the resisitivity iecreased rapidly, and after the stopping the infusing the resistivity decreased slowly. In the saline group, the resisitivity decreased rapidly, and after the stopping the infusing the resistivity increased slowly.In exam group, the region of hematoma can represent clearly higher impedance variation. And during infusing blood, the resisitivity increased rapidly, and after a little decreasing the resistivity increased slowly.
Conclusion
Although the configuration of human head is so complex which limited the application of EIT on the head, it could obtain the definition imaging by polar driver pattern. In the forepart of the ICH, resistivity configuration increased at the region of the hematoma, and the resistivity configuration of the whole head increased too. The mechanism of the resistivity variation might be related with the cerebral-spinal fluid shifting to the further region following the intracranial pressure increasing. Although the detail of the changing rule is still not clear, it might have a widely application in early diagnosis and assistant treatment in clinical.
脑血管意外分为出血性脑血管病和缺血性脑血管病,是危害人类健康的最严重的杀手之一。每年因为脑血管意外引起的死亡人数在人类死亡原因中位列第三位,同时它也是致残率最高的疾病之一。早期诊断和早期治疗是降低脑血管意外致死率和致残率最好的办法,随着医学辅助技术的发展,尤其是CT和MRI的问世,大大解决了脑血管意外的早期诊断问题,也使得治疗取得了长足的进步。以往的观点认为脑出血,尤其是高血压脑出血的出血过程是单时像过程,很快就会停止,但是越来越多的证据表明血肿的进行性扩大以及再次出血的情况并不少见,这样临床症状的观察以及反复的辅助检查就成为脑出血患者进展期的唯一手段。但是由于现有的影像学检查办法如CT、MRI、TCD等仅仅能显示一个固定的时间点的颅内资料,无法提供一个连续的影像学资料,在两次复查CT之间只能通过医生观察临床症状和生命体征来判断病情有无变化,因此临床上迫切需要一种能够实时提供颅内血肿变化的监护系统。生物电阻抗是生物体的基本属性之一,电阻抗断层成像系统可以提供生物体电阻抗的变化情况。由于电阻抗断层成像技术具有无创无害、成本低廉、操作简便、功能成像等优点,适于进行长时间的图像监护。本实验在猪脑出血模型中应用生物电阻抗断层成像系统实时监护脑出血后猪脑内电阻抗变化状况,旨在提出一种能够实时观察颅内变化的新的监护系统。
材料与方法
物理模型试验采用一个半球形容器内放置一个用以模拟颅骨的内石膏壳构成。在球壳内注入饱和CaSO4溶液模拟脑组织和头皮。在半球形容器的内侧壁以等间隔的方式安放16个电极,用与血液电阻率一致的琼脂块来模拟血液在石膏壳模拟的颅腔内移动,观察EIT系统对血液信号的敏感性。
实验动物采用体重15公斤左右的小猪28只,雌雄不限,术前12小时禁食,4小时禁水。其中打开颅骨状态下注射自体不抗凝动脉血4只,注射生理盐水组8只,注射蒸馏水组8只,保持颅腔完整性注血组8只。采用速眠新和3%戊巴比妥钠复合麻醉,术中给于维持量的戊巴比妥(10mg/kg·h),采用自体血注入的猪额叶脑出血模型。以双眼内龇连线为基准线,层距2mm行CT冠状扫描。根据CT扫描结果,选取双眼外眦连线旁正中1cm处为穿刺点并用颅钻钻孔。取股动脉血10ml,沿钻好的穿刺孔穿刺,进针2cm,用微量泵以40ul/s的速度将5ml动脉血(生理盐水或蒸馏水)在3分钟内注入猪脑。1小时后行CT复查,并计算血肿量。
EIT测量采用16导联测量法,以猪头最长横径和前后径分别为长短径形成一个圆形的近似颅脑外界,将16个电极等间隔放置。注血前后实时连续监测至少30分钟。
手术结束后将动物深度麻醉处死,完整取脑组织行大体观察。手术过程采用无菌术,手术过程用恒温毯保持动物体温在38.5度。
结果:
1物理模型结果提示模拟血液的琼脂块由“颅腔”内移动过程中,成像结果能相对较好地反映模型中出血区域的大小及位置。
2所有动物造模均成功,出血模型血肿位置位于右侧额叶皮质下,大小为4.88±0.12ml。CT检查显示血肿形成,大体标本提示血肿形成,符合脑出血急性期病理改变。注蒸馏水及生理盐水模型大体可见注水针道位于脑额叶白质内。
3 EIT结果背景期图像显示脑EIT值均一。去除颅骨注血组注血开始后,在注血区域可见明显的电阻抗值降低区域,注血停止后,电阻抗值缓慢回升。注射生理盐水组注射开始后,可见明显的信号降低区域,随注水量的增加逐渐降低,随后电阻抗维持一段时间的逐渐回升,注射蒸馏水组注射开始后,可见明显的信号升高区域,随注水量的增加逐渐升高,维持一段时间后逐渐回落;闭合式注血组注血开始后,在注血区域可见明显的电阻抗值升高区域,注血停止后,电阻抗缓慢下降;
结论
通过物理模型实验,发现EIT成像结果能相对较好地反映模型中出血区域的大小及位置。通过对去除颅骨后猪颅内注入非抗凝血模型的EIT监护研究,发现随着出血量的不断增加,出血灶区域的阻抗断层图像显示阻抗值逐渐降低。通过对猪颅内注入生理盐水、蒸馏水实验说明EIT图像能灵敏地反映猪颅内阻抗降低和升高的变化。通过闭合式猪颅内注入非抗凝血模型的建立及EIT监护实验图像的变化,提示颅内出血与颅内压的变化有显著相关、颅内压的变化及其代偿机制客观存在脑出血后颅内压变化的动态过程需要研究。
Background and objective
Stroke includes two types: intracranial hemorrhage and brain infarction. It is one of the grisly killers of the people’s health. And it is one of the most common and dangerous disease with very high mortality & disability rate in alive people. Early detection and diagnosis are the keys to increase the survival rate and decrease the complications of the intracranial hemorrhage (ICH). Following the development of medical imageology, especially the CT and MRI application, early diagnosis became easy and facility and strength assist the earlier treatment. Former viewpoint about the intracranial hemorrhage deemed that the process of the brain hemorrhage was a single vector course, and would stop quickly. But the newer viewpoint considered that this process might be a incessancy process or appear repeated, and those was be approved during the clinical experience. Therefore the repeated clinical symptom observed and assistants examined are obligatory. However, nowadays imaging facility (CT, MRI, TCD et al) only offers incontinuous data, and can not persistent offer the correlative data. During the period of former and latter CT scans, surgeons obtain the accurate clinical data only through the clinical syndromes and heart electricity and breath monitor system. It brings much inconvenient and might affect the treatment in time. Consequently it pressed for a new monitor system that could supply the hemorrhage process in real time in clinical.
Electrical bio-impedance is one of the instinctual properties of the organism. Electrical Impedance Tomography (EIT) can provide the variety of the electrical impedance during the pathological process. For EIT technique has the advantages of harmless,low cost, easy to use and functional imaging. Those features make it more fit for long time imaging monitoring. Therefore, in this study, we arrange to image monitoring the intracranial hemorrhage animal model use EIT technique. And try to obtain a new system for monitoring the skull’s impedance variation.
Material and method
We place a plaster hemispherical shell into a hemispherical container to simulate the skull layer and filling the container with CaSO4 saturated solution to simulate the scalp and the brain tissues. The resistivity disturbance was made by immersed an agar to simulate the disturbance caused by blood. In animal model experiment, we use animal model with the instrument of EIT to study the resistance changes of the brain in acute ICH. 28 piglets (weight 15 kg) were were deprived of food and water overnight before the experimental procedure. And all the animal were divided into four groups, one group including 4 animals infusing artery blood deprived the skull and scalp;the others group including 8 animals in each one: the second group infusing artery blood, the control groups infusing distilled water and saline separately. After anesthetized successes, a cranial burr hole (1.5 mm) was then drilled 10 mm to the right of the sagittal and 10 mm anterior to the coronal suture. A 7.5-gauge sterile plastic trocar (length 19 mm) was then placed stereotaxically into the center of the frontal cerebral white matter at the level of the caudate nucleus and cemented in place. An infusion pump was then connected, and 5 ml of blood (distilled water or saline) was infused into the brain tissue at a rate of 40μl per second within 3 minutes.
16 Ag/AgCl electrodes were placed on the scalp of piglets annularly. The centre of a circle was located on the cross of the joining line of two lateral-canthi and the median line of the head. The semidiameter of the circle was 7-8cm. All of the electrodes were located on the circumference orderly. Before the blood infusing, we monitored the foreground at least for 60 frames. After the blood infusion was finished, we continuously collected the data for at least 30 minutes. After EIT monitor finished, we had an X-ray CT (GE Company) scan to validate the model. At the same time, the volume of the hematoma was calculated according to the CT imaging. All surgical procedures were performed with the use of aseptic techniques. Core temperature was measured with a rectal thermistor probe and was maintained at 38.5±0.5°C with the use of a warm water blanket.
Result
The results in physical model show that the skull handicapped the detection of resistivity disturbance inside cranial greatly. And in animal model expericment, in the group of infusing blood with deprived the skull and scalp, the resisitivity decreased rapidly, and after the stopping the infusing the resistivity increased slowly; in the distilled water, the resisitivity iecreased rapidly, and after the stopping the infusing the resistivity decreased slowly. In the saline group, the resisitivity decreased rapidly, and after the stopping the infusing the resistivity increased slowly.In exam group, the region of hematoma can represent clearly higher impedance variation. And during infusing blood, the resisitivity increased rapidly, and after a little decreasing the resistivity increased slowly.
Conclusion
Although the configuration of human head is so complex which limited the application of EIT on the head, it could obtain the definition imaging by polar driver pattern. In the forepart of the ICH, resistivity configuration increased at the region of the hematoma, and the resistivity configuration of the whole head increased too. The mechanism of the resistivity variation might be related with the cerebral-spinal fluid shifting to the further region following the intracranial pressure increasing. Although the detail of the changing rule is still not clear, it might have a widely application in early diagnosis and assistant treatment in clinical.
引文
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