数字化虚拟肝脏及其手术的研究
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摘要
背景
     肝癌是常见病和多发病,在1990年时为全球第四位癌症杀手,而2000年则上升为第三位,每年新增加病例100万人以上,每年死于肝癌的患者约26万人,其中我国占42.5%,并且自20世纪90年代即为第二位癌症杀手。肝癌恶性程度高,外科手术治疗目前仍然是治愈肝癌的最有效方式也是首选方式。中晚期患者,肝癌切除率约20%~30%,5年生成率51.6%。肝癌外科手术需要医生对肿瘤的大小、形状、位置以及与肝脏管道结构的关系有详细的了解。现在对肝脏肿瘤的形态学诊断手段主要靠CT、MRI等影像设备,而这些医疗仪器只能提供人体内部的二维图像,医生只能凭经验由多幅二维图像去估计病灶的大小及形状,“构思”病灶与其周围结构的三维几何关系,这给肝脏疾病的形态学诊断和手术治疗带来了困难,导致肝脏肿瘤手术切除率低,一些可能切除的肿瘤病变没有切除。同时由于肝癌患者往往伴有乙型肝炎、肝硬化等,肝功能存在一定程度的损伤,甚至处于代偿的边缘,要求外科医生在适合作手术的患者行手术治疗时,最大限度切除肿瘤,同时也要最大限度的减少手术对正常组织不必要的创伤,保留肝脏的功能,降低手术的并发症,提高患者术后的生活质量。失出切除手术机会的患者如何进行综合治疗,具体怎样选择来延长生存时间,提高生活质量。如何对这些治疗方式的选择和疗效进行评价等等,均需要一个综合系统来进行治疗规划、治疗过程的模拟、治疗结果的预测和综合评估。
     医学图像可视化和虚拟现实技术进行数字化三维重建虚拟肝脏及其外科手术的研究为解决这些难题带来了希望。数字化虚拟肝脏及其手术是利用CT,MRI等图像序列进行处理,构造出能显示肝脏各结构的三维几何模型,将看不见的人体器官能以三维形式“真实”地显示出来。它的优点是在空间中具有准确的定位,可以立体地从各个角度观察和测量各解剖结构、测量各种数据,促进肝脏临床解剖学的发展,同时虚拟肝脏的各种手术,并可以利用具体肝脏肿瘤患者的影像学(CT、MRI等)检查数据进行图像融合和更新,这样可以让外科医师在计算机上进行手术规划,反复演练手术过程并优化手术方案,提高手术技能,提高手术的安全性,降低手术并发症。
     目的
     研究三维重建数字化虚拟肝脏、肝脏血管栓塞和肝脏切割手术仿真系统的方法。
     方法
     1.肝脏CT扫描图像数据集可视化和血管栓塞手术仿真的研究
     1)肝脏CT扫描图像数据集
     (1)肝门部保留完好的完整肝脏,用灌注材料分别对肝动脉,门静脉、下腔静脉/肝静脉、胆管系统进行灌注和固定,然后行螺旋CT薄层扫描,获取CT扫描图像数据集。
     (2)使用ITK(Insight Toolkit)将CT薄层扫描图像从DICOM格式转换为BMP格式。
     (3)分析肝脏图像中管道结构特征。
     2)基于肝脏管道骨骼线的可视化研究
     (1)对CT图像进行二值化预处理。
     (2)使用面绘制MC算法重建肝脏及其内部管道结构表面模型,并对模型进行平滑和简化。
     (3)从预处理后的体数据场中确定出管道树上的关键节点,并使用改进的种子生长法生成管道树。
     (4)将生成的管道的表面模型和管道树相结合实现交互式分析。
     3)肝脏血管栓塞手术仿真系统的研究。
     将可视化技术研究成果与肝癌的栓塞治疗过程中的关键技术结合起来,建立一套可以用于肝癌血管栓塞治疗的术前规划和术后验证的医学虚拟环境系统。系统输入的为CT图像数据集,重建肝脏实质与其内部管道。血管栓塞模拟时,在三维场景中进行人工的交互,通过血管的拓扑结构进行立体定位仿真,通过所选择的血管栓塞部位,控制栓塞范围,模拟栓塞后治疗效果。
     4)建立立体视觉的虚拟环境显示系统
     建立了主动式和被动式两种立体显示系统。在OpenGL中修改肝脏管道模型投影变换矩阵,生成具有差异的两幅图像,通过主动式和被动式立体显示系统,让观众左右眼分别看到其中的一幅图像,而产生具有深度感的立体图像。
     2.肝脏切割手术仿真的研究
     1)肝脏管道灌注后切片图像数据集及其特征:肝门部保留完好的完整肝脏,以不同颜色的灌注材料分别对肝动脉,门静脉、下腔静脉/肝静脉、胆管系统进行灌注、固定,然后进行包埋、冰冻和铣切,获取连续肝脏断面图像数据集。
     2)切片图像三维可视化
     (1)图像配准:本实验采用外部点力和力矩法相结合,利用包埋时预先埋在肝脏附近的标志物作为配准点对图像进行配准。
     (2)图像分割:主要针对肝静脉和门静脉,具体方法是:(Ⅰ)高斯—拉普拉斯算子在图中提取出所有的轮廓线,其中既有肝脏的轮廓,也有管道的轮廓。(Ⅱ)轮廓线进行膨胀和细化操作使轮廓线上的断点愈合。(Ⅲ)对各条轮廓线所包含的组织类型进行判断:(ⅰ)如果颜色偏红,则全涂成红色,标注为门静脉。(ⅱ)如果颜色偏蓝,则全涂成蓝色,标注为肝静脉。(ⅲ)否则涂成棕色,标注为肝实质。各图像经分割后,肝实质、肝静脉和下腔静脉、门静脉、肝动脉、胆道和胆囊的图像信息被分别提取出来。
     (3)三维重建:使用三维重建软件MINICS 9.0,采用面绘制的方法建立肝脏及其内部管道结构的表面三维形态模型,输出模型格式为STL格式,为虚拟手术的研究做准备。
     3)虚拟手术系统
     在自由设计模型系统(FreeForm Modeling System)基础上二次开发,利用系统附带的基础开发软件GHOST开发出虚拟切割的软件,然后利用系统的力反馈设备PHANTOM,操纵模拟手术刀对肝脏模型可以进行随意的切割,建立虚拟肝脏切割手术环境系统,并对肝脏左外叶肿瘤切除手术的不同方式和右半肝切除术进行了模拟。
     结果
     1.肝脏CT扫描图像可视化和血管栓塞手术仿真的研究
     1)肝脏管道灌注标本螺旋CT薄层扫描数据集:共获得242张CT扫描图像,每张图像显示肝内管道(肝静脉和门静脉)结构信息,与肝实质组织形成明显的对比。中间部位图像分别可见下腔静脉,肝右、中、左静脉和肝段的门静脉分支。肝门部图像可见门静脉及其分支。
     2)基于管道骨骼线的肝脏可视化
     重建的肝脏模型具有肝脏、肝静脉、门静脉和胆囊结构,形态逼真,立体感强。能对模型放大、缩小和旋转全方位观察各结构。能通过节点的选择控制节点所属的“管道树枝”的透明度和颜色设定来单独或组合显示肝脏及其管道结构各部分。
     3)肝脏血管栓塞手术仿真系统
     在肝脏血管栓塞手术仿真演示系统中,通过节点的选择控制节点所属的“管道树枝”,并结合透明度和颜色的设定来显示或隐藏管道结构,模拟肝脏血管栓塞手术的栓塞部位、范围和模拟栓塞后结果。
     4)立体视觉的虚拟环境显示系统
     在主动式和被动式两种立体显示系统中,戴上各自专用的立体液晶眼镜后,肝脏模型就好像从电脑显示器或银幕中突出来,立体感强,各结构空间位置明确,有种身临其境的感觉,看到的每一个画面都像在自己身边发生似得,交互性好。
     2.肝脏切割手术仿真的研究
     1)肝脏切片数据集:共获取肝脏连续肝脏断面图像910张,图像清晰,肝动脉、门静脉、下腔静脉/肝静脉、胆管系统分别显示红色、棕红色、黑色、蓝色。
     2)肝脏三维重建:
     (1)图像配准:配准的图像在1100×900的矩形区域,最大限度显示肝脏的全貌。
     (2)图像分割:对胆囊、管道和肝脏实质分别进行分割,提取表面轮廓线,获得相应的图像。
     (3)三维重建:重建的肝脏模型立体形态逼真,可以放大、缩小和旋转。
     3)虚拟肝脏切割手术系统
     在建立的虚拟肝脏切割手术虚拟环境系统中,沉浸感强,交互性好。可以使用力反馈设备PHANTOM对立体肝脏模型进行随意的控制,包括放大、缩小、全方位旋转等等;可以通过PHANTOM操纵“虚拟手术刀”对肝脏模型进行随意地切割。对左外叶肿瘤切除手术和右半肝切除术的模拟,过程和结果基本符合临床实际情况。
     结论
     1.采用CT图像,基于肝脏管道骨骼线的方法进行肝脏及其管道系统三维重建可视化肝脏,生成肝脏和内部管道系统,以及在此基础上开发的血管栓塞手术仿真系统,交互性好,有助于肝脏临床解剖学的发展和肝脏血管栓塞手术的研究。
     2.利用肝脏管道系统灌注后切片数据集,采用面绘制的方法重建肝脏及其管道系统的三维模型,在力反馈设备的基础上进行虚拟肝脏切割手术的研究,交互性、沉浸性和构象性好,模拟肝切除手术的过程和结果均比较理想,基本达到了比较满意的程度,取得了初步的结果,对推进肝脏临床外科手术学研究的发展有重要意义。
Hepatoma, a widespread disease covering major population, was rated the No. 4 fatal disease across the world in 1990, and escalated to be the No. 3 in 2000. Each year the patients increase 1 million, whilst it causes 260 thousand patients to death, with 42.5% from China. Since the 90~(th) of twenty century, it has become the No.2 fatal disease in China. Due to the dangerousness of the Hepatoma, surgery is the most preferred and most effective treatment solution. Among the medium and late phase liver cancer patients, 20-30% of them get a surgical liver resection while the 5-year recovery rate reaches 51.6%. The success of liver cancer surgery requires the surgeon to have a comprehensive understanding of the tumor's size, shape, location and the relationship to intrahepatic vessel. Currently the equipment employed for diagnosing the liver tumor mainly includes such image devices as CT and MRI. However, such devices could only provide two-dimensional images on the inside of human body. Surgeon could only estimate the size and shape of lesions based on personal experience through several two-dimensional images, "figuring out" the 3-dimensional relationship between lesions and the surrounding vessel structure. It makes difficulties for the morphologic diagnosis of liver disease and the surgery treatment., causing a low rate of the liver resections and leaving more and more Hepatoma un-removed as expected. Meanwhile, since the liver cancer patients normally get Hepatitis B and hepatic cirrhosis which cause injury to their liver function, make it close to compensation. Hence, when conducting surgery, the surgeon needs to ensure not only resect the liver lesion completely, but he/she needs minimize the unnecessary injury caused by the operation to the normal tissues. The surgery also needs to protect the function of the liver, prevent the complication caused by the operation, and enhance the life quality after the surgery. The question is how to prolong the survival time so as to improve the life quality of the patients with unresectable liver cancer, by choosing the appropriate comprehensive therapy. In order to answer the question as well as to assess the outcome of the selected therapeutic strategies, the comprehensive system construction is required for the therapeutic protocol design, treatment process mimics and efficacy evaluation and prediction.
     3-dimensional reconstruction of liver and the virtual surgery research through visualization and the virtual reality have made it possible to solve such problems. The digital virtual liver and the surgery makes use of such imagery sequence as CT and MRI, so as to display a 3-dimensional model of the various structures of the liver, making the hiding human organ a visible "live" 3-dimensional object. The strengths include: 1) being specifically located in certain space; 2) Being observable in structure and being measurable and available in various data; 3) Enhancing the advancement of anatomical liver. In various surgeries of virtue liver, the CT or MRT examination data of specific liver cancer patients could be employed for image fusion and updating. Hence the surgeons can use their computers to conduct surgical planning, to repetitively test the operational process. Such computerization exercise will help surgeons to optimize the planning, to ensure the surgery quality and safety, and to reduce the operation complications.
     Objective
     To investigate the methodology of three-dimensional reconstruction, hepatic vascular embolism system of the digitalized virtual liver and its neoplasmic surgical resection mimic system.
     Methods
     1. The research on visualization of liver CT scanning and simulation of vasculature embolism.
     1) The CT image dataset of liver
     (1) The liver with well preserved the portal region was perfused with filling materials in different colors through hepatic artery, portal vein, inferior vena cava/hepatic vein and bile vessel and scanned by hispeed CT to obtain the image dataset.
     (2) The format of CT images was converted from DICOM to BMP by ITK (Insight Toolkit).
     (3) Analyzing the intrahepatic duct structural feature on CT images.
     2) Visualizing investigation on hepatic vessel structure based upon skeleton line extraction
     (1) CT images were preprocessed in binary way.
     (2) The Marching Cube (MC) algorithm, a kind of surface rendering, were employed to reconstruct 3D surface models of liver and intrahepatic ducts, and then these 3D surface models were smoothed and simplified.
     (3) The abstract vessel trees were constructed, after the skeleton line of the vessel system were extracted from the hepatic CT dataset.
     (4) The extracted vessel tree was combined with the vessel surface model for analyzing the vessel structure interactively.
     3) The research of simulation on vasculature embolism.
     Applying the liver visualization technique to the clinic of vasculature embolism, a virtual medical system was established for the therapeutic protocol planning and testing the efficacy evaluation of hepatic vasculature embolism, which construct surface models of liver and intrahepatic duct using CT images. When hepatic vasculature embolism was simulated, the vasculature knob points was selected and regulated to locate embolism and confine its affected area.
     4) Virtual stereovision environment was built
     Both the active and passive sets of virtual stereovision environment were built, which enables the audience watch altered transformation matrix of liver model by OpenGL with his or her separate naked right/left eye in stereogram with vertical extent consequently.
     2. The research on simulation of partial hepatectomy.
     1) The image dataset and its characteristics: The entire liver with complete porta hepatis was prepared, followed by infusing, fixing and casting the hepatic artery, portal veins, inferior vena cava, bile duct system using filling materials in different colors. Then it was embedded, frozen and slice-cut by a milling machine so as to obtain the image dataset of liver serial sections.
     2) Visualization of liver
     (1) Image registration: In our experiment, image registration was conducted by external point force combined with moment-to-force. The markers pre-embedded around the liver were set as registration points and the image registration was performed based on the relatively-fixed positions between the liver and those markers.
     (2) Image segmentation: It mainly aimed at the segmentation of hepatic and portal veins. The procedures included: (Ⅰ) Gaussian-Rapras algorithm was used to extract all the contour line of both liver and ducts. (Ⅱ) The contour line were expanded and refined to connect their broken lines. (Ⅲ) The type of tissues incorporating in the contours was judged and identified by fully marking the portal veins with red color if they were reddish, fully marking the hepatic veins with blue color if they were bluish and finally marking the liver parenchyma with brown color if they were neither reddish nor bluish. Following the segmentation of all images, the image data of liver parenchyma, hepatic veins and inferior vena cava, portal veins, hepatic artery, bile duct and cholecyst were all extracted, respectively.
     (3) 3D reconstruction: The 3D reconstruction software MINICS (Materialise' s interactive medical image control system) was used to reconstruct 3D liver model with hepatic surface in surface rendering.
     3) The virtual surgery system
     Based on the FreeForm Modeling System, the software of virtual resection was developed. And then the virtual hepatectomy system was established with the force-feedback equipment (PHANTOM), which can manipulate the virtual scalpel to perform optional resection on virtual liver model.
     Results
     1. The research on visualization of liver and simulation of vasculature embolism.
     1) The CT scanned image dataset of liver
     242 scanned images of liver were taken. Each image showed relevant hepatic duct conformations. Inferior vena cava, the right, middle and left hepatic veins could be seen clearly in the image through porta hepatis, and portal veins and its branches could be seen clearly in the image through porta hepatis.
     2) Visualization of hepatic vessel structure based on skeleton line extraction
     In the reconstituted liver model, the images of liver parenchyma, hepatic veins and portal veins were vividly displayed respectively or in combination. This visible system of liver provided a graphics user interface to rotate and scale the 3D liver to observe 3D morphological features of the liver and intrahepatic duct by setting the pellucidit value and colors.
     3) The research on simulation of vasculature embolism
     In the demo system of vasculature embolism simulation, the vasculature embolic position, scope and its consequences were simulated by manipulating the nodal points of intrahepatic trees.
     4) Virtual stereovision environment
     In the two systems, when audience in special glasses watch liver model, it looks like flying in the sky from computer screen or viewing screen with strength stereo.
     2. The research of simulation on partial hepatectomy.
     1) The dataset of hepatic sectional images: After slice cutting cast liver and by a milling machine, 910 serial cross-section images were obtained and they were sharp and clear, with hepatic artery, portal veins, inferior vena cava/hepatic veins, bile duct system displayed in red, brownish red, black and blue.
     2) Visualization of liver
     (1) Image registration: The registered images were within the rectangular area of 1100×900, which ideally demonstrated the full view of the liver
     (2) Image segmentation: The image information of cholecyst, intrahepatic ducts and hepatic parenchyma were respectively segmented and their contour line was extracted.
     (3) 3D reconstruction: The 3D reconstructed liver model looks like the liver sample, and can be magnified, contracted and rotated.
     3) The virtual partial hepatectomy system
     In the virtual surgery system with interaction and immersion, we can manipulate the virtual scalpel to perform optional resection on 3D liver model with the haptic device (PHANTOM).
     Conclusions
     1. 3D liver model with intrahepatic vessel, which was 3-dimensionally reconstructed in the method of skeleton line using CT scanning images, may be helpful in the promotion of hepatic clinical anatomy. Based on 3D reconstruction, a simulative system of vasculature embolism developed, which addresses fully interaction facilities, may be helpful in the research of simulation on vasculature embolism.
     2. The 3D visualized liver has been satisfactorily developed with the method of surface rendering using the hepatic serial sectional images. Then based on the haptic devices (PHANTOM) the virtual hepatectomy system has been developed, which has good interaction, powerful immersion and great imagination, may be of great significance for the promotion of hepatic clinical surgery.
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