血流速度对脉冲高强度聚焦超声消融肝组织的影响
发布时间：2018-08-05 13:33
【摘要】：研究背景 目前，高强度聚焦超声（high intensity focused ultrasound，HIFU）治疗技术在临床上的应用是对病灶进行高功率的连续波辐照，利用其热效应对靶组织进行消融治疗。脉冲高强度聚集超声（pulsed highintensity focused ultrasound，PHIFU）与现有的HIFU发射连续波消融组织不同，其治疗方式是脉冲式，由脉冲辐照时间和间歇时间组成。前期实验研究发现PHIFU能够产生明显的空化效应，引起靶区组织损伤。 PHIFU作为一种间歇辐照方式，可能会减少连续波辐照对靶区声通道上因能量沉积而产生的正常组织损伤。作为一种潜在的新治疗模式，PHIFU消融肿瘤的组织学变化及其靶区超声影像学特征，血流速度对PHIFU消融效果的影响是临床应用该治疗模式前的一个重要研究内容。本课题应用临床HIFU肿瘤治疗设备，拟在离体猪肝灌注模型上，通过调节肝灌注流量来观察PHIFU消融肝组织的凝固性坏死体积变化和B超声像图特征，以及肝血管对PHIFU消融效果的作用，探讨血流速度和血管对PHIFU消融肝组织的影响及其靶区超声影像学变化，为HIFU临床应用提供新的治疗模式和参数。 目的 1.探讨血流速度对PHIFU消融肝组织的影响及其靶区超声影像学变化。 2.探讨血管对PHIFU消融肝组织的影响和血管的损伤变化。 方法 1.不同肝灌注流量下PHIFU消融肝组织的特征及其超声影像图变化 实验动物:猪肝由屠宰场提供，家猪被处死后2～3min内取出肝脏，建立经门静脉、肝动脉和下腔静脉进行灌流的离体猪肝灌注模型，达到灌注要求后待用。 实验方法 （1）以连续波HIFU辐照为对照组，PHIFU辐照为实验组。辐照参数设定：脉冲重复频率100Hz，辐照功率80W，深度20mm。实验组占空比20%，，辐照时间25s，对照组占空比100%，辐照时间10s。通过调整体外循环机中门静脉转流泵的转速，使门静脉的流量分别为442mL/min、588mL/min、746mL/min、886mL/min。 （2）在不同灌注流量下，应用PHIFU定点辐照离体灌注肝脏。实验组在辐照过程中应用B超实时观察靶区声像图变化，分析靶区灰度变化的规律，每组实验重复20次。 （3）PHIFU辐照后，切开灌注肝组织，找到靶区组织最大的损伤面，测量并记录坏死区域的损伤情况，计算凝固性坏死体积，局部取材，观察靶区的组织学变化。 2.肝血管对PHIFU消融肝组织的影响 实验方法： (1)采用HIFU脉冲波（实验组）和连续波（对照组）两种辐照方式，辐照参数分别为声功率80W、占空比20%、辐照时间50s和声功率80W、占空比100%、辐照时间10s，辐照深度为40mm，脉冲重复频率为100Hz。 （2）通过HIFU机载超声寻找适合的治疗层面，找到管径为4mm左右的血管，分别将血管、距离血管前、后方3mm处的肝组织定位为靶区，采用定点辐照靶区肝脏，每组实验重复15次。 （3）辐照后切开肝组织，找到靶区最大的损伤面，测量并记录坏死区域，计算凝固性坏死体积，肉眼观察两组靶区肝组织和血管的损伤情况，分别取材，观察组织学变化。 结果： 1. PHIFU消融肝组织的损伤特点：与连续波HIFU辐照相同，PHIFU组靶区肝组织均出现凝固性坏死的特征性变化，损伤区和非损伤区边缘清晰，损伤区内未发现有明显的空洞形成。 2. PHIFU消融肝组织的超声影像学变化：PHIFU辐照离体灌注肝脏时，B超能实时显示靶区组织灰度的变化，主要表现为靶区灰度从无到有、逐渐增强、然后减弱、并再增强的动态变化过程。在不同灌注流量下，靶区声像图开始出现灰度变化的时间不同，灌注流量增加可以延迟辐照过程中声像图靶区灰度变化的出现。 3. PHIFU靶组织坏死体积与灌注流量关系：门静脉灌注流量为442mL/min、588mL/min、746mL/min、886mL/min时，实验组靶区凝固性坏死体积分别是157.41±5.79mm3、118.70±5.96mm3、72.97±6.04mm3和44.45±3.49mm3；对照组靶区凝固性坏死体积分别是156.41±6.23mm3、120.57±6.44mm3、74.39±7.62mm3和45.96±5.72mm3，表明随着肝血流量的增加，靶区坏死体积逐渐减少，两者之间呈负相关关系。相同流量下，实验组与对照组比较差异无统计学性意义（P0.05）。 4. PHIFU靶组织坏死体积与血管关系：两组邻近血管的靶区组织均出现凝固性坏死的特征性变化。与对照组比较，PHIFU组靶区凝固性坏死体积明显增加。其中，实验组和对照组在靶区位于血管后方的坏死体积分别为79.72±4.94mm3和25.53±2.08mm3，靶区位于血管前方的坏死体积分别为85.6±10.23mm3和28.34±7.28mm3，两组比较，差异均具有显著的统计学性意义（P0.05）。 5. PHIFU对靶区邻近血管的损伤作用：实验组和对照组分别对血管，血管前、后方靶区肝组织辐照后，肉眼观察两组靶区，均未发现明显的血管损伤表现，血管经HE染色和维多利亚蓝和丽春红血管纤维染色，光镜下观察见血管壁结构完整，内皮细胞和血管壁纤维组织未出现损伤。 结论： 1. PHIFU消融肝脏的组织学变化表现为典型的凝固性坏死，损伤区和非损伤区边缘清晰。 2. PHIFU辐照过程中，B超能实时观察靶区声像图灰度的变化,呈现灰度增强、减弱，再增强的动态变化过程。 3.血流速度能影响PHIFU消融肝组织的效果，随着肝血流速度的增加，靶区坏死体积逐渐减少；同时，血流速度增加可以延迟辐照过程中声像图靶区灰度变化的出现。 4. PHIFU能用比连续波HIFU更少的能量达到相似的损伤体积。 5.与连续波HIFU辐照比较，PHIFU能明显增加靠近血管靶区的凝固性坏死体积。 6. PHIFU对血管或者靶区邻近血管均无明显的直接损伤作用。
[Abstract]:Research background
At present, the clinical application of high intensity focused ultrasound (high intensity focused ultrasound, HIFU) therapy is a high power continuous wave irradiation on the focus, using its thermal effect to ablation the target tissue. Pulse high intensity aggregation ultrasound (pulsed highintensity focused ultrasound, PHIFU) is continuous with the existing HIFU emission. The treatment of wave ablation is different, and its treatment is pulse type, which is composed of pulse irradiation time and intermittent time. Earlier experimental study found that PHIFU could produce obvious cavitation effect and cause tissue damage in target area.
As a kind of intermittent irradiation, PHIFU may reduce the normal tissue damage caused by the energy deposition on the target acoustic channel by continuous wave irradiation. As a potential new therapeutic model, the histological changes of PHIFU ablation and the ultrasound imaging features of the target area, the effect of blood flow velocity on the effect of PHIFU ablation is clinical application. An important research content before the treatment model. This subject uses the clinical HIFU tumor treatment equipment to observe the changes of the volume of coagulation necrosis and the characteristics of the B-ultrasound image by regulating the perfusion flow of the liver in the isolated pig liver perfusion model, as well as the effect of the liver blood vessels on the effect of PHIFU ablation, and to explore the velocity of blood flow and blood. The effect of catheter on PHIFU ablation of liver tissue and the changes of target ultrasound imaging provide a new therapeutic mode and parameters for the clinical application of HIFU.
objective
1. to investigate the effect of blood flow velocity on PHIFU ablation of liver tissue and the changes of target ultrasound.
2. to investigate the effect of blood vessel on PHIFU ablation of liver tissue and vascular injury.
Method
1. the characteristics and ultrasonographic changes of PHIFU ablation liver tissue under different hepatic perfusion flow rate
Experimental animals: pig liver was provided by a slaughterhouse. The liver was removed from 2 to 3min after the death of the pig. The liver perfusion model of the porcine liver was established through the portal vein, the hepatic artery and the inferior vena cava.
Experimental method
(1) the control group was irradiated by continuous wave HIFU, and PHIFU irradiated as the experimental group. The radiation parameters were set: pulse repetition frequency 100Hz, irradiation power 80W, depth 20mm. experimental group 20%, irradiation time 25s, control group duty cycle 100%, and irradiation time 10s. by adjusting the speed of portal vein bypass pump in the extracorporeal circulation machine, so that the flow of portal vein was respectively 442mL/min, 588mL/min, 746mL/min, 886mL/min.
(2) under the different perfusion flow, the liver was perfused in vitro by PHIFU fixed-point irradiation. In the process of irradiation, the experimental group was used to observe the changes of the target image in real time by B-ultrasound, and to analyze the law of the change of the target area in the target area, and the experiment was repeated 20 times in each group.
(3) after PHIFU irradiation, the liver tissue was incised and perfused to find the largest injury surface of the target tissue, and the damage of the necrotic region was measured and recorded. The volume of coagulation necrosis was calculated, the local material was obtained, and the histological changes in the target area were observed.
The effect of 2. hepatic vessels on PHIFU ablation of liver tissue
Experimental methods:
(1) two radiation modes of HIFU pulse wave (experimental group) and continuous wave (control group) are used. The radiation parameters are sound power 80W, occupying ratio 20%, irradiation time 50s and sound power 80W, occupying ratio 100%, irradiation time 10s, irradiation depth 40mm, and pulse repetition rate of 100Hz.
(2) to find the suitable treatment level by HIFU airborne ultrasound, the blood vessels with a diameter of about 4mm were found. The blood vessels, the distance from the blood vessels, and the liver tissues at the rear 3mm were located as the target area respectively. The target liver was irradiated at fixed points, and the experiment was repeated 15 times in each group.
(3) after irradiation, the liver tissue was cut, the maximum damage surface of the target area was found, the necrotic area was measured and recorded, the volume of coagulation necrosis was calculated. The damage of the liver tissue and blood vessels in the two groups of target areas was observed by the naked eye, and the histological changes were observed.
Result:
1. PHIFU ablation of liver tissue: the same as continuous wave HIFU irradiation, the liver tissue in the target area of group PHIFU had the characteristic changes of coagulation necrosis, the edge of the damaged area and the non damaged area was clear, and no obvious cavity formation was found in the damaged area.
2. PHIFU ablation of liver tissue ultrasound imaging changes: when PHIFU irradiated in vitro perfusion liver, B-ultrasound can show the changes in the gray level of the target tissue in real time. The main manifestation is that the gray level of the target area is gradually increased, then the dynamic change process is strengthened and then strengthened. When the time is different, the increase of perfusion rate can delay the appearance of the gray level change of the target in the process of irradiation.
3. PHIFU target tissue necrosis volume and perfusion flow relationship: portal venous perfusion flow is 442mL/min, 588mL/min, 746mL/min, 886mL/min, the volume of coagulation necrosis in the target area of the experimental group is 157.41 + 5.79mm3118.70 + 5.96mm3,72.97 + 6.04mm3 and 44.45 + 3.49mm3 respectively, and the volume of coagulative necrosis in the target area of the control group is 156.41 + 6.23mm3120.57 respectively. 6.44mm3,74.39 + 7.62mm3 and 45.96 + 5.72mm3 showed that the necrosis volume of target area decreased gradually with the increase of hepatic blood flow, and there was a negative correlation between the two groups. There was no statistical difference between the experimental group and the control group (P0.05) under the same flow rate.
4. PHIFU target tissue necrosis volume and blood vessel relation: the target area of two groups of adjacent vessels all appeared the characteristic change of coagulation necrosis. Compared with the control group, the volume of coagulation necrosis in the target area of the PHIFU group was obviously increased. The bad dead volume of the experimental group and the control group in the target area behind the vessels was 79.72 + 4.94mm3 and 25.53 + 2.08mm, respectively. 3. The necrosis volume of the target area in front of the blood vessel was 85.6 (+ 10.23) mm3 and 28.34 (+ 7.28) mm3, respectively. The difference between the two groups was statistically significant (P 0.05).
The effect of 5. PHIFU on the injury of the adjacent vessels in the target area: the experimental group and the control group irradiated the blood vessels, anterior vessels and the rear target area respectively. No obvious vascular damage was found in the two groups of target areas. The blood vessels were stained with HE and Vitoria blue and Lichun red blood vessel fibers. The vascular wall structure was observed under the light microscope. No damage was found in the skin cells and the fibrous tissue of the vascular wall.
Conclusion:
1. the histological changes of the PHIFU ablation liver showed typical coagulative necrosis, and the edges of the injured area and the non injured area were clear.
2. In the process of PHIFU irradiation, B-mode ultrasound can observe the change of the gray level of the target sonogram in real time, showing the dynamic process of gray level enhancement, weakening, and reinforcing.
3. the velocity of blood flow can affect the effect of PHIFU ablation on the liver tissue. With the increase of the velocity of the liver blood flow, the necrosis volume of the target area decreases gradually. At the same time, the increase of the velocity of blood flow can delay the appearance of the gray change in the target area of the sound image during the irradiation.
4. PHIFU can achieve similar damage volume with less energy than continuous wave HIFU.
5. compared with continuous wave HIFU irradiation, PHIFU significantly increased the coagulation necrosis volume near the vascular target area.
6. PHIFU had no obvious direct damage to blood vessels or adjacent vessels in target area.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R730.55
本文编号：2165950
[Abstract]:Research background
At present, the clinical application of high intensity focused ultrasound (high intensity focused ultrasound, HIFU) therapy is a high power continuous wave irradiation on the focus, using its thermal effect to ablation the target tissue. Pulse high intensity aggregation ultrasound (pulsed highintensity focused ultrasound, PHIFU) is continuous with the existing HIFU emission. The treatment of wave ablation is different, and its treatment is pulse type, which is composed of pulse irradiation time and intermittent time. Earlier experimental study found that PHIFU could produce obvious cavitation effect and cause tissue damage in target area.
As a kind of intermittent irradiation, PHIFU may reduce the normal tissue damage caused by the energy deposition on the target acoustic channel by continuous wave irradiation. As a potential new therapeutic model, the histological changes of PHIFU ablation and the ultrasound imaging features of the target area, the effect of blood flow velocity on the effect of PHIFU ablation is clinical application. An important research content before the treatment model. This subject uses the clinical HIFU tumor treatment equipment to observe the changes of the volume of coagulation necrosis and the characteristics of the B-ultrasound image by regulating the perfusion flow of the liver in the isolated pig liver perfusion model, as well as the effect of the liver blood vessels on the effect of PHIFU ablation, and to explore the velocity of blood flow and blood. The effect of catheter on PHIFU ablation of liver tissue and the changes of target ultrasound imaging provide a new therapeutic mode and parameters for the clinical application of HIFU.
objective
1. to investigate the effect of blood flow velocity on PHIFU ablation of liver tissue and the changes of target ultrasound.
2. to investigate the effect of blood vessel on PHIFU ablation of liver tissue and vascular injury.
Method
1. the characteristics and ultrasonographic changes of PHIFU ablation liver tissue under different hepatic perfusion flow rate
Experimental animals: pig liver was provided by a slaughterhouse. The liver was removed from 2 to 3min after the death of the pig. The liver perfusion model of the porcine liver was established through the portal vein, the hepatic artery and the inferior vena cava.
Experimental method
(1) the control group was irradiated by continuous wave HIFU, and PHIFU irradiated as the experimental group. The radiation parameters were set: pulse repetition frequency 100Hz, irradiation power 80W, depth 20mm. experimental group 20%, irradiation time 25s, control group duty cycle 100%, and irradiation time 10s. by adjusting the speed of portal vein bypass pump in the extracorporeal circulation machine, so that the flow of portal vein was respectively 442mL/min, 588mL/min, 746mL/min, 886mL/min.
(2) under the different perfusion flow, the liver was perfused in vitro by PHIFU fixed-point irradiation. In the process of irradiation, the experimental group was used to observe the changes of the target image in real time by B-ultrasound, and to analyze the law of the change of the target area in the target area, and the experiment was repeated 20 times in each group.
(3) after PHIFU irradiation, the liver tissue was incised and perfused to find the largest injury surface of the target tissue, and the damage of the necrotic region was measured and recorded. The volume of coagulation necrosis was calculated, the local material was obtained, and the histological changes in the target area were observed.
The effect of 2. hepatic vessels on PHIFU ablation of liver tissue
Experimental methods:
(1) two radiation modes of HIFU pulse wave (experimental group) and continuous wave (control group) are used. The radiation parameters are sound power 80W, occupying ratio 20%, irradiation time 50s and sound power 80W, occupying ratio 100%, irradiation time 10s, irradiation depth 40mm, and pulse repetition rate of 100Hz.
(2) to find the suitable treatment level by HIFU airborne ultrasound, the blood vessels with a diameter of about 4mm were found. The blood vessels, the distance from the blood vessels, and the liver tissues at the rear 3mm were located as the target area respectively. The target liver was irradiated at fixed points, and the experiment was repeated 15 times in each group.
(3) after irradiation, the liver tissue was cut, the maximum damage surface of the target area was found, the necrotic area was measured and recorded, the volume of coagulation necrosis was calculated. The damage of the liver tissue and blood vessels in the two groups of target areas was observed by the naked eye, and the histological changes were observed.
Result:
1. PHIFU ablation of liver tissue: the same as continuous wave HIFU irradiation, the liver tissue in the target area of group PHIFU had the characteristic changes of coagulation necrosis, the edge of the damaged area and the non damaged area was clear, and no obvious cavity formation was found in the damaged area.
2. PHIFU ablation of liver tissue ultrasound imaging changes: when PHIFU irradiated in vitro perfusion liver, B-ultrasound can show the changes in the gray level of the target tissue in real time. The main manifestation is that the gray level of the target area is gradually increased, then the dynamic change process is strengthened and then strengthened. When the time is different, the increase of perfusion rate can delay the appearance of the gray level change of the target in the process of irradiation.
3. PHIFU target tissue necrosis volume and perfusion flow relationship: portal venous perfusion flow is 442mL/min, 588mL/min, 746mL/min, 886mL/min, the volume of coagulation necrosis in the target area of the experimental group is 157.41 + 5.79mm3118.70 + 5.96mm3,72.97 + 6.04mm3 and 44.45 + 3.49mm3 respectively, and the volume of coagulative necrosis in the target area of the control group is 156.41 + 6.23mm3120.57 respectively. 6.44mm3,74.39 + 7.62mm3 and 45.96 + 5.72mm3 showed that the necrosis volume of target area decreased gradually with the increase of hepatic blood flow, and there was a negative correlation between the two groups. There was no statistical difference between the experimental group and the control group (P0.05) under the same flow rate.
4. PHIFU target tissue necrosis volume and blood vessel relation: the target area of two groups of adjacent vessels all appeared the characteristic change of coagulation necrosis. Compared with the control group, the volume of coagulation necrosis in the target area of the PHIFU group was obviously increased. The bad dead volume of the experimental group and the control group in the target area behind the vessels was 79.72 + 4.94mm3 and 25.53 + 2.08mm, respectively. 3. The necrosis volume of the target area in front of the blood vessel was 85.6 (+ 10.23) mm3 and 28.34 (+ 7.28) mm3, respectively. The difference between the two groups was statistically significant (P 0.05).
The effect of 5. PHIFU on the injury of the adjacent vessels in the target area: the experimental group and the control group irradiated the blood vessels, anterior vessels and the rear target area respectively. No obvious vascular damage was found in the two groups of target areas. The blood vessels were stained with HE and Vitoria blue and Lichun red blood vessel fibers. The vascular wall structure was observed under the light microscope. No damage was found in the skin cells and the fibrous tissue of the vascular wall.
Conclusion:
1. the histological changes of the PHIFU ablation liver showed typical coagulative necrosis, and the edges of the injured area and the non injured area were clear.
2. In the process of PHIFU irradiation, B-mode ultrasound can observe the change of the gray level of the target sonogram in real time, showing the dynamic process of gray level enhancement, weakening, and reinforcing.
3. the velocity of blood flow can affect the effect of PHIFU ablation on the liver tissue. With the increase of the velocity of the liver blood flow, the necrosis volume of the target area decreases gradually. At the same time, the increase of the velocity of blood flow can delay the appearance of the gray change in the target area of the sound image during the irradiation.
4. PHIFU can achieve similar damage volume with less energy than continuous wave HIFU.
5. compared with continuous wave HIFU irradiation, PHIFU significantly increased the coagulation necrosis volume near the vascular target area.
6. PHIFU had no obvious direct damage to blood vessels or adjacent vessels in target area.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R730.55
【参考文献】
相关期刊论文 前9条
1 龚志锦;阮静;陶文照;;显示弹性、胶原纤维的双重组合染色法[J];动物学杂志;1993年02期
2 葛鹏磊;李宁;;高强度聚焦超声治疗肝癌致皮肤烧伤的原因及预防[J];临床超声医学杂志;2007年10期
3 苏静;陈文直;;高强度聚焦超声对血管作用的研究进展[J];临床超声医学杂志;2008年02期
4 贺雪梅;熊欣;邹建中;李发琪;马平;王智彪;;高强度聚焦超声辐照靶区回声强度与温度的相关性实验研究[J];临床超声医学杂志;2008年04期
5 任新英;徐志新;陈春玲;庞云;;离体猪肝体外循环灌注用于治疗急性肝衰模型的建立[J];新疆医科大学学报;2009年07期
6 刘春梅;陈锦云;柯丹;徐杰;雷令;李发琪;王智彪;;工作周期对脉冲高强度聚焦超声辐照离体牛肝的影响[J];中国超声医学杂志;2007年08期
7 邱冬;费兴波;龙劲松;舒江乔;孟军;纵林;王艳;李锦香;潘振芳;王仁香;;高强度聚焦超声治疗子宫肌瘤的疗效观察[J];中华医学超声杂志(电子版);2008年03期
8 郑元义,王志刚,冉海涛,张群霞,李晓东,凌智瑜,卢岷,任红;诊断超声加微泡造影剂对新生血管的作用[J];中国医学影像技术;2004年03期
9 何炜;王维;周平;周鹏;;HIFU非热效应诱导兔肝VX2肿瘤损伤[J];中国医学影像技术;2010年12期
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