微机辅助CT灌注成像
CT Perfusion Mapping
近年来，有关CT脑灌注成像和定量测量的临床应用报道日益增多[1-8]。在对急性脑梗死的诊断中，CT脑灌注成像和定量测量的作用已得到充分肯定。由于目前国外CT厂商均将脑灌注成像软件包作为图形工作站中的选件，报价较高，因此限制了CT脑灌注成像在国内的广泛应用。为了使这项新技术在国内得到更好的应用和发展，我们在前期工作[1, 2]的基础上，根据中心容积定理(central volume principle)的理论，对CT原始图像的DICOM 3.0标准格式进行了研究，并以Windows98为平台、Vissual C++为开发语言，设计了在微机上使用的CT脑灌注成像及定量测量程序。现将这一研究的初步结果报告如下。
Recently reports on the clinical implementation of CT perfusion mapping and quantitative measurement have increased dramatically[1-8]. The advantages of CT perfusion mapping and quantitative measurement for the diagnosis of acute cerebral infarction have been acknowledged. However, as most overseas CT vendors set perfusion mapping software package as an option for graphic workstation, the price is usually too expensive for domestic practitioners. To foster the domestic implementation and development of this new technology, we have, based on our overture preparations[1, 2] and subject to the theory of Central Volume Principle, studied DICOM3.0 standard forms of prime CT images, and developed CT perfusion mapping and quantitative measurement programs for PCs with Windows98 and Visual C++. Following is the preliminary report on our study.
材料与方法
Materials and Methods
一、 设计思想
由于PACS和MiniPACS已在国内部分医院放射科投入运行，而且越来越多的医院也将安装PACS，因此我们的设计思想是先经放射科内的PACS网络及程序将病人的动态增强CT扫描图像的DICOM 3.0标准格式数据下载到微机上，启动CT脑灌注成像及定量测量程序，在动态CT图像上分析并计算脑血流动力学的有关参数，包括脑血流量(cerebral blood flow, CBF)、脑血容量(cerebral blood volume, CBV)、平均通过时间(mean transit time, MTT)和峰值时间(time to peak, TTP)等。最后，根据色阶分别形成脑血流量图(mapping of CBF)、脑血容量图(mapping of CBV)、平均通过时间图(mapping of MTT)和峰值时间图(mapping of TTP)。由于程序处理的对象是以DICOM 3.0标准格式的CT图像数据，因此用任何支持DICOM 3.0标准的CT机作动态增强扫描后，将原始图像以DICOM 3.0标准格式传入微机即可进行脑灌注成像和定量测量。
A. Development Ideas
In China, the radiological departments in some hospitals have already implemented PACS and MiniPACS, and some other hospitals are going to implement PACS. Therefore, our idea is to download the dynamic CT images of a patient in DICOM3.0 standard form onto a PC via PACS network and programs of the radiological departments. Then CT perfusion mapping and quantitative measurement programs shall be started to analyze and compute related parameters of cerebral hemodynamics on dynamic CT images, including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and mapping of time-to-peak (TTP). As the processing objects are CT images data in the standard form of DICOM3.0, any CT machine supportive for DICOM 3.0 standard can be employed for dynamic scanning. Then the prime images shall be transmitted to a PC for perfusion mapping and quantitative measurement in the standard form of DICOM 3.0.
二、 系统环境
1．硬件配置 IBM PC兼容机一台，配有pentium II 300MHz微处理器、128MB内存、16MB显存、6G硬盘、100MB以太网网卡和15英寸显示器。操作系统为Windows 98第二版。
2．软件设计 根据中心容积定理用Vissual C++作为开发语言进行程序编写。全部图像处理过程包括：
1）DICOM 3.0标准动态CT扫描图像数据读入 考虑到动态扫描时CT和高压注射器的时间配合问题以及不同年龄患者血流速度不同等因素的影响，当选择数据读入功能后，由使用者根据窗口提示自行选择需要读入的文件及数量。这样的好处是可以调节“时间变空间”灌注图像（平均通过时间图和峰值时间图）的颜色。当患者血流缓慢或扫描与注药时间匹配有问题致使对比剂到达扫描层面而连续动态扫描已经超过全部层数的1/3时，“时间变空间”图像颜色将位于色阶的中上段。此时，使用者删除位于前面的若干幅动态CT图像，可使“时间变空间”图像颜色在色阶上下移。数据读入自选功能可以在平均通过时间图和峰值时间图的空间上保证脑血流时间信息不改变的前提下，纠正由于CT和高压注射器的时间配合不当或患者生理性血流缓慢所造成的图像颜色偏差。
2）参数设定 使用者可根据实际情况设定TTP图像、CBF图像、CBV图像和MTT图像的参数，以便达到最佳显示效果。
3）分割颅骨、皮下组织和脑室 为了达到良好的显示效果，本程序采用半自动方式分割颅骨、皮下组织和脑室。首先用鼠标勾画出大致范围，然后点击菜单项上的功能按钮，程序将自动去除颅骨、皮下组织和脑室。
4）图像显示 本程序可以显示动态扫描中的第一幅CT图像、全部动态图像中最大密度图像、TTP图像、CBF图像、CBV图像和MTT图像。为了显示原始结果，程序中未作平滑处理。
5）定量测量 用鼠标双击某一区域，程序可以自动描绘出该区域的时间-密度曲线，并自动计算出TTP值、CBF值、CBV值和MTT值。
2. Software designs. Based on Central Volume Principal, Visual C++ has been employed as development language for program compilation. The whole graphic processing course includes:
1) Loading of dynamic CT images in standard form of DICOM 3.0. In view of the match of time of dynamic CT scanning and the power injector, and of the blood flow differences between patients with different ages, the user shall select the documents and the quantity according to the instructions in the window after selecting the data input function. In this way, the colors of “time-to-space” perfusion mapping (MTT and TTP) can be adjusted. When the blood flow of a patient is too slow or the scanning does not match with the injection time, and the contrast medium reaches the scanning layer with consecutive dynamic scanning exceeding 1/3 of the total layers, the image color of “time-to-space” is located in the middle/upper section of the colour gradation. At this point, the user can move down the image color of “time-to-space” on the color gradation by eliminating the several dynamic CT images in front. The optional data input function can correct the image color error caused by ill match of the time of CT and the power injector or the physiological slow blood flow of the patient without changing the cerebral blood flow time data on the space of the mapping of MTT and mapping of TTP.
2) Parameter settings. The user can, subject to practices, set the parameters for mapping of TTP, mapping of CBF, mapping of CBV and mapping of MTT for optimal display effects.
3) Separation of the skull, hypoderm and ventricles. For better display effects, this program has employed a semi-automatic method to separate the skull, the hypoderm and the ventricles. First, a general range shall be sketched out with the mouse, then click the function button on the menu, and the program will automatically separate the skull, the hypoderm and the ventricles.
4) Image display. Of the whole dynamic scanning, this program can display the first CT image, the most dense image, TTP images, CBF images, CBV images and MTT images. To display the prime results, this program has not undergone smoothing processing.
5) Quantitative measurement. Double click a certain area, the program will automatically describe the time-density curve of the area, and automatically compute its TTP value, CBF value, CBV value and MTT value.
三、 CT检查程序
CT检查程序为首先进行常规CT平扫，然后根据病史选择感兴趣层面进行动态增强扫描，动态扫描后再行常规增强扫描。感兴趣区层厚10mm，扫描矩阵512X512，曝光kv和ms与常规扫描相同。动态CT检查方法为在启动高压注射器经肘静脉快速注入对比剂的同时对感兴趣层面进行连续快速扫描。曝光时间为1秒，连续扫描40秒，共40层。碘对比剂为300mg碘海醇，每秒注射8ml，总量为40ml。
B. CT Examination Program
The CT examination program is: first to conduct the routine horizontal scanning; then interested sections will be chosen according to the case history for a dynamic scanning; a routine enhanced scanning will follow the dynamic scanning. The thickness of the interested section is 10mm, image matrix 512x512, exposure kv and ms are the same with a routine scanning. 40 mL nonionic contrast agent was administered with a constant flow rate of 8 mL/s via the antecubital vein by using a power injector. Each 360° rotation took 1 second, and the total acquisition time was 40 seconds. From this data set, a series of images with a time interval of 1 second was reconstructed, corresponding to 40 images.
结 果
脑组织的CBF、CBV、TTP和MTT灌注原始图像见图1-4。分割颅骨、皮下组织和脑室后的图像见图5-8。图9-10为同一病人的MR图像，图11－12为平扫CT和强化后CT。常规CT和MR检查仅可见皮层下动脉硬化性脑病，CT灌注图像可见明显的脑局部血流缓慢（图3，4，7，8）。
Results
Please refer to Pictures 1 - 4 for the prime images of CBF, CBV, TTP and MTT perfusion mapping. Please refer to Pictures 5 - 8 for images separated from the skull, the hypoderm and the ventricles. Pictures 9 –10 are MR images of the same patient, Pictures 11 – 12 are horizontal CT image and enhanced CT image. Routine CT and MR examinations can only detect infracortical cerebral arteriosclerosis, whereas CT perfusion mapping images can detect evident slowed down cerebral focal blood flow (Pictures 3, 4, 7, 8)
讨 论
Discussion
人类脑的正常生理性功能活动以及各种病理性活动与脑血流变化密切相关，因此获取人类活体脑组织微循环血流的信息一直是影像医学中一个令人感兴趣的领域。目前在活体上测定脑组织灌注的影像学方法包括正电子发射体层摄影（positron emission tomography, PET）、单光子发射体层摄影（single photon emission computed tomography, SPECT）、氙－CT（Xe-CT）、MR灌注成像和CT灌注成像等。由于设备或辅助设备昂贵、检查费用高以及很难得到定量数据等原因，上述方法还没有在临床广泛应用。
The normal physiological functions of the human brain closely correlate with a variety of pathological activities and the changes in cerebral blood flows. Therefore, the acquisition of information on viviperception of cerebral micro-cycling blood flow has always been gripping in the field of the medical science of mapping. Presently the mapping methods to determine cerebral perfusion on living objects include positron emission tomography (PET), single photon emission computed tomography (SPECT), Xe-CT, MR perfusion mapping and CT perfusion mapping etc. Due to expensiveness of the equipments, auxiliary equipments and examination charges, and the difficulty to obtain quantitative data, the above methods are not in extensive clinical usages yet.
利用动态CT测定脑组织血流灌注量的理论基础，来源于核医学数据处理技术[1, 2]。将放射性示踪剂静脉团注，经左室到达某器官后，通过动态扫描，可获得示踪剂首次通过该器官的时间-放射性曲线。增强CT扫描中经静脉注入的对比剂，其药代动力学改变与示踪剂类似，因此这种方法也可用于动态CT的研究。1983年Axel[9]首次利用动态CT扫描技术和对比剂团注射法获得了脑的CBF和CBV定量数值。由于受当时CT扫描速度原因的限制，此项技术没有在临床应用。近年来，随着CT技术的不断提高和改进，使得此项技术越来越实用化[1-8]。注入对比剂后动态CT图像中动脉及组织的时间-密度曲线的横坐标为时间，纵坐标为注药后增加的CT值，其变化反映的是对比剂在该器官中浓度的变化，即碘聚集量的变化，从而反映了组织灌注量的变化。由于1mg/ml的碘浓度相当于25HU，则1mg碘相当于25HU·ml，即1mg碘可使1ml组织的CT值增加25HU。因此，注入对比剂的量可用HU·ml来表示，这样，通过测定局部脑组织的碘聚集量，即可获得局部脑组织的血流灌注量。中心容积定理反应了CBF、CBV和MTT三者之间的关系：CBF=CBV/MTT。根据计算我们可以得到局部脑组织血流灌注的定量数据。脑CT灌注成像主要通过团注碘对比剂显示毛细血管内对比剂通过时引起脑组织密度变化状态。团注碘对比剂到达脑组织后使脑组织密度逐渐升高，在一定时间内达到密度峰值后逐渐下降，最后恢复到使用对比剂之前的密度水平。将不同时间脑组织的密度值连成曲线，即可得到对比剂通过脑组织的时间-密度曲线。通过分析时间-密度曲线可以得到TTP、CBF、CBV和MTT等血液动力学参数。根据动态CT图像中所有象素的时间-密度曲线，计算出所有象素的上述四个指标后，采用彩色编码技术就可以得到脑组织的TTP、CBF、CBV和MTT灌注图像。用鼠标点击这些灌注图像上任何感兴趣区可以得到感兴趣区的TTP、CBF、CBV和MTT定量数值。
The theoretical foundation to determine cerebral blood flow perfusion volume via dynamic CT lies in data processing technology of nuclear medical science[1, 2]. Mass injected via a vein, the radioactive tracer agent reaches a certain tissue through the left ventricle. With the dynamic scanning, the time-radioactivity curve of the tracer agent when it passes through the tissue for the first time will be obtained. The pharmacokinetic change of the contrast agent injected into a vein during the enhanced CT scanning is similar with that of the tracer agent, therefore this method can also be employed for the studies of dynamic CT. In 1983, Axel[9] obtained for the first time quantitative values of CBF and CBV by dynamic CT scanning technology and contrast agent mass injection method. Restrained at that time by the rate of CT scanning, the technology was not implemented clinically. Recently, with the improvement of CT technology, this technology is becoming more and more practical[1-8]. The contrast agent having been injected, the abscissa of the time-density curve of the artery and the tissue in the dynamic CT image is the time, and the ordinate is the increased CT value after the injection. The change of the ordinate reflects the density change of the contrast agent in the tissue, viz. the change in the aggregate amount of iodine, thus the change in tissue perfusion amount. As the iodine density of 1mg/ml equals to 25HU, 1mg iodine equals to 25HU·ml, viz. 1mg iodine can increase the CT value of 1ml tissue by 25HU. Therefore, the amount of injected contrast agent can be reflected in HU·ml. By this way, the perfusion amount of regional cerebral blood flow can be obtained with the determination of the aggregate amount of iodine in the section. The Central Volume Principle reflects the correlations between CBF, CBV and MTT: CBF=CBV/MTT. We can obtain the quantitative data of regional cerebral blood flow perfusion via computations. With the mass injection of iodine contrast agent, cerebral CT perfusion mapping displays cerebral density changes caused by the contrast agent when it passes through capillary vessels. When the mass injected iodine contrast agent reaches the brain, its density gradually increases, then reduces after it reaches the peak value. Eventually it retrieves to the density before the contrast agent arrives. Connect the cerebral density values of different times into a curve, and a time-density curve is obtained regarding the passage of the contrast agent in the brain. TTP, CBF, CBV, MTT and other hemodynamic parameters can be obtained from this time-density curve analysis. The four above indexes of all pixels shall be computed according to the time-density curve of dynamic CT images. Then, the TTP, CBF, CBV and MTT perfusion mapping images can be obtained with colored coding technology. The quantitative values of TTP, CBF, CBV and MTT can be obtained by clicking on any of the interested section on these perfusion mapping images,.
CT灌注成像相对简单易行，与MR灌注成像相比更适于急诊检查。临床上，早期脑梗死病人的首选检查方法为常规CT，其目的主要是显示脑内是否有出血。如果没有脑内出血，则按照脑缺血进行治疗。由于常规CT很难在在脑梗死发作8小时之内有阳性发现，因此脑CT灌注成像在早期脑梗死的诊断上具有重要意义[3, 6-8]。近年来多层CT技术的出现弥补了以往脑CT灌注成像仅仅能观察一个层面的缺点，使得这项技术具有了重要的临床实用价值。此外，我们研制的微机辅助CT脑血流灌注成像软件是一个绿色软件，仅有一个文件，安装后对计算机软件系统无任何影响，经半年试用，对急性缺血性脑血管病的早期诊断上取得了很好的临床效果。我们相信，此软件的推广和应用可为临床医师提供可视化程度高、脑血流动力学信息更为丰富的工具。对于没有PACS的CT室，可先通过网线将微机与CT机连接好后，用eFilm软件（可通过互联网下载）获取动态CT的文件（DICOM 3.0格式），然后在微机上继续处理这些图像文件从而得到脑CT灌注图。
Easy and accessible, CT perfusion mapping is more appealing for emergency examinations than MR imaging. Clinically, the ideal examination method for early cerebral infarction patients is routine CT aiming to detect whether there is any intracerebral hemorrhage. The case shall be treated as cerebral ischemia if no intracerebral hemorrhage incurs. As routine CT is rather incapable of positive detection within 8 hours after a cerebral infarction attack, CT perfusion mapping is of great significance for the diagnosis of early cerebral infarctions[3, 6-8]. Recently, with the introduction of multi-layer CT technology, CT perfusion mapping is no longer only capable of single-section scanning. The clinical practicability of this technology has been greatly optimized. Further, the PC-auxiliary CT CBF perfusion mapping software package developed by us is green and environmental friendly. The single document it contains does not have any negative effects to the software system of a PC. Satisfactory clinical results have been yielded for the early diagnosis of acute cerebrovascular ischemia during its half a year trial period. We believe that, with higher visualization and more cerebral hemodynamics information, this software package will be handy for clinical doctors. For CT departments that do not have PACS yet, the CT machine shall be connected with the PC via a grid line, dynamic CT documents (in DICOM 3.0 form) can be obtained via eFilm (downloadable from the Internet). Then these documents shall be processed on a PC to get CT perfusion mapping images.
计算机辅助诊断(computer aided diagnosis，CAD)可以提高医生诊断水平。CAD在影像医学领域中应用的核心是将各种影像设备产生的图像进行定量分析，找出医生诊断所需要的各种数据，然后将其与人的生理参数测量数据一起进行综合分析，最后根据医生的需求完成对图像数据的再显示，从而达到提高诊断水平的目的。在上述过程中，定量分析是实现计算机辅助影像诊断的核心。由于CAD扩大了医生有限的个人知识和经验，提高了医生个体有限的精力和视力，因此可以使诊断变得更为精确，更为科学。正是基于这样的认识，我们利用微机辅助CT脑灌注成像以及定量测量，提高了对超急性脑梗死的影像诊断水平。
Computer aided diagnosis (CAD) improves the diagnostic ability of a doctor. The core of CAD implementation in the field of mapping is to analyze quantitatively the images generated by mapping equipments, to locate data needed for the diagnosis, and to analyze these data comprehensively with the physiological parametric measurement data of the patient. Finally, for a more optimal diagnostic result, these graphic data will be re-displayed according to the requirements of the doctor. During this course, quantitative analysis is the core for the realization of CAD. CAD improves the personal knowledges and experiences of a doctor, and complements his/her energy and perception, making the diagnosis more accurate and scientific. Based on such ideas, we have carried out computer aided CT perfusion mapping and quantitative measurement so as to improve the mapping diagnostic ability for super acute cerebral infarction.
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