双能量CT评价肝细胞癌形成过程的血管生成
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摘要
目的：
应用双源CT双能量技术研究肝硬化向肝细胞癌发展过程中不同阶段结节(肝硬化结节RN,不典型增生结节DN,肝细胞癌HCC)内血管生成状态。重点研究双能量CT碘图在肝细胞癌形成过程中血管生成状态中的应用。
材料与方法：
选择我院2010年8月到2011年4月间临床上拟诊为肝硬化肝细胞癌而需要进行肝移植术治疗的肝移植受体26例(A组)纳入本研究,另设26例普通增强扫描的对照组(B组)。所有病人均于肝移植术前接受受体影像学评估,应用双源CT双能量技术扫描全肝,肝移植术后对切除的受体肝脏进行详细的病理学评估。病理学评估包括大体病理与HE染色评估和免疫组化(CD34,VEGF染色)评估,采用WeiDNer法进行MVD计数,以免疫反应积分(IRS)定量描述VEGF的表达。本研究采用SOMATOM Definition Dual source CT (DSCT; Siemens, Forchheim, Germany)双源CT系统对病人进行常规平扫和双能量动脉期(20-25s),门脉流入期(45-55s),门脉期(80-90s),延迟期(300s)四期增强扫描。扫描完成后,对所获得的影像进行常规评价,重点对双能量碘图进行肉眼评价和定量评价：组织有无增强及增强程度以橙色,红色的有无和深浅来判断；将大小约为1.0cm2的兴趣区(region of interest, ROI)分别放置在由动脉期、门脉流入期、门脉期和延迟期双能量碘图上,测量不同病理性质的病灶内碘图强化的定量指标(碘图强化值)。并记录各期辐射剂量值CT剂量加权指数(computed tomography dose index, CTDIvol),剂量长度乘积(dose length product, DLP)和有效剂量(effective dose, ED)。
结果：
大体病理及HE染色结果：26例肝移植受体共获得41个结节,其中肝硬化结节RN8个,不典型增生结节DN10个,小肝癌HCC23个
免疫组化结果：全部8个肝硬化结节RN的CD34,VEGF染色均呈阴性。不典型增生结节DN的平均MVD为56.5±12.9,VEGF IRS值为6.5±1.2。肝细胞癌HCC的平均MVD为74.1±17.8,VEGF IRS值为11.2±0.8。
CT影像发现：
肝硬化结节RN在双能量碘图上结节的颜色与周围肝实质颜色相同,呈暗红色,四期增强均未见强化。四期碘图强化值分别为：0.6±0.7,1.0±0.5,1.7±1.0,2.0±0.9。
不典型增生结节DN：9例动脉期和门脉流入期,门脉期均未见强化,延迟期双能量碘图上表现为较周围肝脏实质的颜色稍暗。1例在动脉期双能量碘图上表现为半圆形亮红色强化区,而在门脉流入期碘图上表现为橙红色强化区,门脉期及延迟期碘图上呈现与周围肝脏实质相似的暗红色。四期碘图强化值分别为：1.1±0.8,1.4±1.2,2.0±1.0,1.7±0.6。
肝细胞肝癌HCC：22个结节动脉期结节呈橙黄色,但其亮度不及同层腹主动脉的亮度；门脉流入期呈红色,与周围橙黄色的肝脏相比颜色较暗或相同；门脉期及延迟期结节的颜色较周围暗红色的肝脏实质还要暗。1个HCC结节动脉期与肝脏相似的红色,门脉期和延迟期均比周围肝脏的颜色暗。碘图强化值分别为：2.7±0.7,2.3±0.8,2.4±1.1,1.8±0.9。
统计结果
将所得结节按照病理性质分为三组：再生结节RN组,不典型增生结节DN组,肝细胞癌HCC组。将26例接受双能量检查的病人归为A组,另外26例接受普通增强CT检查的病人归为B组。
①三组间微血管密度的差异有统计学意义(F=4.041,P<0.001),DN与HCC组间差异有统计学意义(P<0.01)②三组间VEGF IRS差异有统计学意义(F=4.041,P<0.001),DN与HCC组间差异有统计学意义(P<0.01)。③MVD与VEGF IRS值之间呈正相关(r=0.387,P=0.029)。④三组动脉期碘图强化值的差异有统计学意义(F=4.031,P<0.001),HCC组碘图强化值分别与RN及DN组差异有统计学意义(P<0.05),而RN组及DN组之间差异无统计学意义(P>0.05)。⑤三组门脉流入期碘图强化值的差异有统计学意义(F=4.020,P<0.001),HCC组碘图强化值分别与RN及DN组差异有统计学意义(P<0.05),而RN组及DN组之间差异无统计学意义(P>0.05)。⑥三组门脉期碘图强化值差异有统计学意义(F=4.019,P<0.001),HCC组碘图强化值分别与RN及DN组差异有统计学意义(P<0.05),而RN组及DN组之间差异无统计学意义(P>0.05)。⑦三组延迟期碘图强化值差异无统计学意义(P<0.05)⑧MVD与动脉期碘图强化值呈正相关(r=0.545,P<0.001)。⑨VEGFIRS值与动脉期碘图强化值呈正相关(r=0.405,P<0.05)。⑩A,B两组的CT剂量加权指数(computed tomography dose index, CTDIvol),剂量长度乘积(dose length product, DLP)和有效剂量(effective dose, ED)平均值之间差异分别有统计学意义(p<0.05)。采用虚拟平扫代替真实平扫后能够节省约27.4%的辐射剂量。
结论：
双源CT双能量碘图可用于定量评价肝细胞癌形成过程中的血管生成状态。双源CT双能量成像碘图获得的动脉期碘图强化值与MVD和VEGF之间具有正相关性。双能量CT四期增强扫描比常规平扫加四期增强扫描节省约27.4%的辐射剂量。
Objective
To study the angiogenesis in different nodules (regenerative nodules, dysplastic nodules, and hepatocellular carcinoma) existing in the development of hepatocellular carcinoma by using dural source dural energy CT iodine image. To analyse angiogenesis in the development of hepatocellular carcinoma by using the dural-energy CT iodine imaging.
Materials and Methods
Study 26 cases of patients suffered from HCC from auguest 2010 to april 2011, and these patients accepted OLT (orthopedic liver transplantation) soon after the diagnosis. All the patients went through dural-energy CT examination of the livers before surgery. Another 26 cases were examed by routing single energy CT.The pathological detailed evaluation of the explanted cirrhotic livers which included the gross evaluation, HE stain and immunohistochemisty stain (CD34\VEGF) evaluation were carried out after the OLT. The SOMATOM Definition Dual source CT (DSCT; Siemens, Forchheim, Germany) system was used to fulfill the tetra-phase enhancement which included true non-contrast CT scan and dural-energy arterial phase(20-25s)\early portal vein phase (45-55s)\portal vein phase (80-90s)\delayed phase (300s)。The image data acquired was evaluated in a routine way, and special emphasis was put on iodine image. First evaluated by naked eyes:the intensity of enhancement was decided by the color of iodine image (the intensity of enhancement went higher as the color went deeper from red to orange).Then evaluated quantitatively:ROI (region of interest) of about 1.0cm2 was set on the iodine image post-processed from arterial\early portal vein phase\portal vein\delayed phase respectively, in order to record the iodine concentration calculated on iodine image of nodules with different pathological nature. The radiation dose (CTDIvol\DLP\ED) was record as well.
Results
Gross and HE stain evaluation:41 nodules were acquired from 26 cases receptors of OLT. There are 8 RNs (regenerative nodules),10 DNs (dysplastic nodules), and 23 HCCs (hepatocellular carcinoma) respectively. Imunohistochemisty stain (CD34\VEGF) evaluation:CD34\VEGF stains are all negative in 8 RNs. The average MVD and VEGF IRS value of DNs are 56.5±12.9 and 6.5±1.2 respectively。And the values in HCC are 74.1±17.8 and 11.2±0.8 respectively。
CT findings:
All the RNs shows the same red color as the surrounding liver parenchyma,which indicate that there are no enhancement in the tetra-phase enhancement examination. The iodine concentration is:0.6±0.7,1.0±0.5,1.7±1.0,2.0±0.9 respectively. 9 DNs showed no obvious enhancement in arterial\early portal vein phase\portal vein, but showed darker color than the surrounding liver on delayed phase iodine image.1DN appeared crescent-shaped bright red area on arterial phase iodine image, and round orange area on early portal vein phase iodine image, when it comes to portal vein and delayed phase,that area showed the same dark red area as the surrounding liver. The iodine concentration was 1.1±0.8,1.4±1.2,2.0±1.0,1.7±0.6 respectively on tetra-phase enhancement iodine image. 22 HCCs showed orange on artery phase iodine image, but the color was darker than that of abdominal aorta. In early portal vein phase,it is red on iodine image, and the color was darker than that of the surrounding liver. In portal and delayed phase, the liver showed red color on iodine image, and the HCCs showed darker area than the surrounding liver.1 HCC nodule appeared red color just like the liver tissue on artery phase iodine image, but darker color than the surrounding liver on early portal vein phase\portal vein and delayed phase iodine image. The iodine concentration was 2.7±0.7,2.3±0.8,2.4±1.1,1.8±0.9 respectively on tetra-phase enhancement iodine image.
Statistical result
All the nodules were divided into three groups, RN,DN and HCC.
①MVD with differentiation was found to have statistic significance among the three groups (F=4.041, P<0.001), and differentiation between the group of DN and HCC had statistic significance (P<0.01).②VEGF IRS with differentiation was found to have statistic significance among the three groups (F= 4.041, P< 0.001), and differentiation between the group of DN and HCC had statistic significance (P< 0.01).③A direct correlation between MVD and VEGF IRS was found (r=0.387, P = 0.029)④The iodine concentration on the arterial phase iodine image with differentiation was found to have statistic significance among the three groups (F=4.031, P< 0.001), the differentiation between group of HCC and RN had statistic significance (P<0.05), and the differentiation between group of HCC and RN had statistic significance (P<0.05),while the differentiation between group of RN and DN had on statistic significance (P>0.05).⑤The iodine concentration on the early portal vein phase phase iodine image with differentiation was found to have statistic significance among the three groups (F=4.020, P<0.001),the differentiation between group of HCC and RN had statistic significance (P<0.05), and the differentiation between group of HCC and RN had statistic significance (F< 0.05),while the differentiation between group of RN and DN had on statistic significance (P>0.05).⑥The iodine concentration on the portal phase iodine image with differentiation was found to have statistic significance among the three groups(F =4.019, P< 0.001), the differentiation between group of HCC and RN had statistic significance (P<0.05), and the differentiation between group of HCC and RN had statistic significance (P<0.05),while the differentiation between group of RN and DN had on statistic signi ficance(P>0.05).⑦The iodine concentration on the delayed phase iodine image with differentiation was found to have no statistic significance among the three groups (P>0.05).⑧A direct correlation between MVD and the iodine concentration on the arterial phase iodine image was found (r=0.545, P< 0.001)。⑨A direct correlation between VEGF IRS and the iodine concentration on the arterial phase iodine image was found (r=0.405,P<0.05)。⑩the differentiation of CTDIvol\DLP\ED between group of HCC and RN had statistic significance (P< 0.05).by using VNC to replace TNC,about 27.4% of radiation dose could be reduced.
Conclusions
Dural-energy CT iodine image is able to quantitatively evaluate the angiogenesis in the development of hepatocellular carcinoma. The iodine concentration on iodine image post-processed by arterial phase dural-energy CT scan showed direct correlation with MVD and VEGF. Dural-energy CT tetra-phase enhancement could save about 27.4% radiation dose than routine protocol.
应用双源CT双能量技术研究肝硬化向肝细胞癌发展过程中不同阶段结节(肝硬化结节RN,不典型增生结节DN,肝细胞癌HCC)内血管生成状态。重点研究双能量CT碘图在肝细胞癌形成过程中血管生成状态中的应用。
材料与方法：
选择我院2010年8月到2011年4月间临床上拟诊为肝硬化肝细胞癌而需要进行肝移植术治疗的肝移植受体26例(A组)纳入本研究,另设26例普通增强扫描的对照组(B组)。所有病人均于肝移植术前接受受体影像学评估,应用双源CT双能量技术扫描全肝,肝移植术后对切除的受体肝脏进行详细的病理学评估。病理学评估包括大体病理与HE染色评估和免疫组化(CD34,VEGF染色)评估,采用WeiDNer法进行MVD计数,以免疫反应积分(IRS)定量描述VEGF的表达。本研究采用SOMATOM Definition Dual source CT (DSCT; Siemens, Forchheim, Germany)双源CT系统对病人进行常规平扫和双能量动脉期(20-25s),门脉流入期(45-55s),门脉期(80-90s),延迟期(300s)四期增强扫描。扫描完成后,对所获得的影像进行常规评价,重点对双能量碘图进行肉眼评价和定量评价：组织有无增强及增强程度以橙色,红色的有无和深浅来判断；将大小约为1.0cm2的兴趣区(region of interest, ROI)分别放置在由动脉期、门脉流入期、门脉期和延迟期双能量碘图上,测量不同病理性质的病灶内碘图强化的定量指标(碘图强化值)。并记录各期辐射剂量值CT剂量加权指数(computed tomography dose index, CTDIvol),剂量长度乘积(dose length product, DLP)和有效剂量(effective dose, ED)。
结果：
大体病理及HE染色结果：26例肝移植受体共获得41个结节,其中肝硬化结节RN8个,不典型增生结节DN10个,小肝癌HCC23个
免疫组化结果：全部8个肝硬化结节RN的CD34,VEGF染色均呈阴性。不典型增生结节DN的平均MVD为56.5±12.9,VEGF IRS值为6.5±1.2。肝细胞癌HCC的平均MVD为74.1±17.8,VEGF IRS值为11.2±0.8。
CT影像发现：
肝硬化结节RN在双能量碘图上结节的颜色与周围肝实质颜色相同,呈暗红色,四期增强均未见强化。四期碘图强化值分别为：0.6±0.7,1.0±0.5,1.7±1.0,2.0±0.9。
不典型增生结节DN：9例动脉期和门脉流入期,门脉期均未见强化,延迟期双能量碘图上表现为较周围肝脏实质的颜色稍暗。1例在动脉期双能量碘图上表现为半圆形亮红色强化区,而在门脉流入期碘图上表现为橙红色强化区,门脉期及延迟期碘图上呈现与周围肝脏实质相似的暗红色。四期碘图强化值分别为：1.1±0.8,1.4±1.2,2.0±1.0,1.7±0.6。
肝细胞肝癌HCC：22个结节动脉期结节呈橙黄色,但其亮度不及同层腹主动脉的亮度；门脉流入期呈红色,与周围橙黄色的肝脏相比颜色较暗或相同；门脉期及延迟期结节的颜色较周围暗红色的肝脏实质还要暗。1个HCC结节动脉期与肝脏相似的红色,门脉期和延迟期均比周围肝脏的颜色暗。碘图强化值分别为：2.7±0.7,2.3±0.8,2.4±1.1,1.8±0.9。
统计结果
将所得结节按照病理性质分为三组：再生结节RN组,不典型增生结节DN组,肝细胞癌HCC组。将26例接受双能量检查的病人归为A组,另外26例接受普通增强CT检查的病人归为B组。
①三组间微血管密度的差异有统计学意义(F=4.041,P<0.001),DN与HCC组间差异有统计学意义(P<0.01)②三组间VEGF IRS差异有统计学意义(F=4.041,P<0.001),DN与HCC组间差异有统计学意义(P<0.01)。③MVD与VEGF IRS值之间呈正相关(r=0.387,P=0.029)。④三组动脉期碘图强化值的差异有统计学意义(F=4.031,P<0.001),HCC组碘图强化值分别与RN及DN组差异有统计学意义(P<0.05),而RN组及DN组之间差异无统计学意义(P>0.05)。⑤三组门脉流入期碘图强化值的差异有统计学意义(F=4.020,P<0.001),HCC组碘图强化值分别与RN及DN组差异有统计学意义(P<0.05),而RN组及DN组之间差异无统计学意义(P>0.05)。⑥三组门脉期碘图强化值差异有统计学意义(F=4.019,P<0.001),HCC组碘图强化值分别与RN及DN组差异有统计学意义(P<0.05),而RN组及DN组之间差异无统计学意义(P>0.05)。⑦三组延迟期碘图强化值差异无统计学意义(P<0.05)⑧MVD与动脉期碘图强化值呈正相关(r=0.545,P<0.001)。⑨VEGFIRS值与动脉期碘图强化值呈正相关(r=0.405,P<0.05)。⑩A,B两组的CT剂量加权指数(computed tomography dose index, CTDIvol),剂量长度乘积(dose length product, DLP)和有效剂量(effective dose, ED)平均值之间差异分别有统计学意义(p<0.05)。采用虚拟平扫代替真实平扫后能够节省约27.4%的辐射剂量。
结论：
双源CT双能量碘图可用于定量评价肝细胞癌形成过程中的血管生成状态。双源CT双能量成像碘图获得的动脉期碘图强化值与MVD和VEGF之间具有正相关性。双能量CT四期增强扫描比常规平扫加四期增强扫描节省约27.4%的辐射剂量。
Objective
To study the angiogenesis in different nodules (regenerative nodules, dysplastic nodules, and hepatocellular carcinoma) existing in the development of hepatocellular carcinoma by using dural source dural energy CT iodine image. To analyse angiogenesis in the development of hepatocellular carcinoma by using the dural-energy CT iodine imaging.
Materials and Methods
Study 26 cases of patients suffered from HCC from auguest 2010 to april 2011, and these patients accepted OLT (orthopedic liver transplantation) soon after the diagnosis. All the patients went through dural-energy CT examination of the livers before surgery. Another 26 cases were examed by routing single energy CT.The pathological detailed evaluation of the explanted cirrhotic livers which included the gross evaluation, HE stain and immunohistochemisty stain (CD34\VEGF) evaluation were carried out after the OLT. The SOMATOM Definition Dual source CT (DSCT; Siemens, Forchheim, Germany) system was used to fulfill the tetra-phase enhancement which included true non-contrast CT scan and dural-energy arterial phase(20-25s)\early portal vein phase (45-55s)\portal vein phase (80-90s)\delayed phase (300s)。The image data acquired was evaluated in a routine way, and special emphasis was put on iodine image. First evaluated by naked eyes:the intensity of enhancement was decided by the color of iodine image (the intensity of enhancement went higher as the color went deeper from red to orange).Then evaluated quantitatively:ROI (region of interest) of about 1.0cm2 was set on the iodine image post-processed from arterial\early portal vein phase\portal vein\delayed phase respectively, in order to record the iodine concentration calculated on iodine image of nodules with different pathological nature. The radiation dose (CTDIvol\DLP\ED) was record as well.
Results
Gross and HE stain evaluation:41 nodules were acquired from 26 cases receptors of OLT. There are 8 RNs (regenerative nodules),10 DNs (dysplastic nodules), and 23 HCCs (hepatocellular carcinoma) respectively. Imunohistochemisty stain (CD34\VEGF) evaluation:CD34\VEGF stains are all negative in 8 RNs. The average MVD and VEGF IRS value of DNs are 56.5±12.9 and 6.5±1.2 respectively。And the values in HCC are 74.1±17.8 and 11.2±0.8 respectively。
CT findings:
All the RNs shows the same red color as the surrounding liver parenchyma,which indicate that there are no enhancement in the tetra-phase enhancement examination. The iodine concentration is:0.6±0.7,1.0±0.5,1.7±1.0,2.0±0.9 respectively. 9 DNs showed no obvious enhancement in arterial\early portal vein phase\portal vein, but showed darker color than the surrounding liver on delayed phase iodine image.1DN appeared crescent-shaped bright red area on arterial phase iodine image, and round orange area on early portal vein phase iodine image, when it comes to portal vein and delayed phase,that area showed the same dark red area as the surrounding liver. The iodine concentration was 1.1±0.8,1.4±1.2,2.0±1.0,1.7±0.6 respectively on tetra-phase enhancement iodine image. 22 HCCs showed orange on artery phase iodine image, but the color was darker than that of abdominal aorta. In early portal vein phase,it is red on iodine image, and the color was darker than that of the surrounding liver. In portal and delayed phase, the liver showed red color on iodine image, and the HCCs showed darker area than the surrounding liver.1 HCC nodule appeared red color just like the liver tissue on artery phase iodine image, but darker color than the surrounding liver on early portal vein phase\portal vein and delayed phase iodine image. The iodine concentration was 2.7±0.7,2.3±0.8,2.4±1.1,1.8±0.9 respectively on tetra-phase enhancement iodine image.
Statistical result
All the nodules were divided into three groups, RN,DN and HCC.
①MVD with differentiation was found to have statistic significance among the three groups (F=4.041, P<0.001), and differentiation between the group of DN and HCC had statistic significance (P<0.01).②VEGF IRS with differentiation was found to have statistic significance among the three groups (F= 4.041, P< 0.001), and differentiation between the group of DN and HCC had statistic significance (P< 0.01).③A direct correlation between MVD and VEGF IRS was found (r=0.387, P = 0.029)④The iodine concentration on the arterial phase iodine image with differentiation was found to have statistic significance among the three groups (F=4.031, P< 0.001), the differentiation between group of HCC and RN had statistic significance (P<0.05), and the differentiation between group of HCC and RN had statistic significance (P<0.05),while the differentiation between group of RN and DN had on statistic significance (P>0.05).⑤The iodine concentration on the early portal vein phase phase iodine image with differentiation was found to have statistic significance among the three groups (F=4.020, P<0.001),the differentiation between group of HCC and RN had statistic significance (P<0.05), and the differentiation between group of HCC and RN had statistic significance (F< 0.05),while the differentiation between group of RN and DN had on statistic significance (P>0.05).⑥The iodine concentration on the portal phase iodine image with differentiation was found to have statistic significance among the three groups(F =4.019, P< 0.001), the differentiation between group of HCC and RN had statistic significance (P<0.05), and the differentiation between group of HCC and RN had statistic significance (P<0.05),while the differentiation between group of RN and DN had on statistic signi ficance(P>0.05).⑦The iodine concentration on the delayed phase iodine image with differentiation was found to have no statistic significance among the three groups (P>0.05).⑧A direct correlation between MVD and the iodine concentration on the arterial phase iodine image was found (r=0.545, P< 0.001)。⑨A direct correlation between VEGF IRS and the iodine concentration on the arterial phase iodine image was found (r=0.405,P<0.05)。⑩the differentiation of CTDIvol\DLP\ED between group of HCC and RN had statistic significance (P< 0.05).by using VNC to replace TNC,about 27.4% of radiation dose could be reduced.
Conclusions
Dural-energy CT iodine image is able to quantitatively evaluate the angiogenesis in the development of hepatocellular carcinoma. The iodine concentration on iodine image post-processed by arterial phase dural-energy CT scan showed direct correlation with MVD and VEGF. Dural-energy CT tetra-phase enhancement could save about 27.4% radiation dose than routine protocol.
引文
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