Rabbit Liver VX2 Tumor Models Research Articles

Bevacizumab-loaded CalliSpheres beads: in vitro loading, release profiles and application in rabbit liver VX2 tumor model.

Bevacizumab loaded drug-eluting beads have the potential to reduce TACE related VEGF expression. The purpose of this study was to investigate the in vitro loading, and release profiles of bevacizumab (BEV) loaded on Callispheres beads (CB) and its application in rabbit liver VX2 tumor model. CB with sizes of 100-300 um and 300-500 um were divided into 5 groups, respectively. BEV with different content was prepared for CB loading, releasing and detected in the solution at different time points. The diameters of CB in each group were measured under a light microscope to calculate the shrinkage rate. The rabbit with VX2 liver model were divided into control group, CB-TACE group, CB-TACE+BEV group, and BEV group. The data of blood test, CT image, HE and IHC staining were compared and analyzed. The shrinkage rate of the 100-300 um CB was 2.6-7.2%, while the 300-500 um CB was 0.2-7.1%. The BEV-loaded CB (BEV-CB) has a burst release during the first hour and following gradually released with time. The release profiles of 100-300 um CB reach 34% in 24 hours, while the 300-500 um CB to 25.8%. BEV-CB with sizes of 100-300 um was chosen to perform transcatheter arterial chemoembolization (TACE). The results showed that BEV-CB-TACE not only gradually increased the content of BEV in serum and organ tissue but also reduced the level of VEGF in serum. Pathological results suggested that the expression of HIF-1 was elevated while VEGF and MVD decreased when compared to the other groups. In conclusion, this study confirms that Callispheres beads could efficiency loaded BEV. BEV-CB-TACE has a good safety and effectiveness, and its application could reduce the level of VEGF-A in serum in the treatment of VX2 tumors.

Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model.

ObjectivesTo discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard.MethodsTwenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI).ResultsA total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P < 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes.ConclusionsThe TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment.

Abstract No. 506 Image-guided radiofrequency hyperthermia-enhanced direct chemotherapy of hepatic tumors: the underlying biomolecular mechanisms

To evaluate the treatment effects of combined therapy using Doxorubicin and radiofrequency hyperthermia and expound the mechanism of local Chemotherapy under the heat-stress condition in vitro and in a rabbit VX2 liver tumor model Institutional Animal Care and Use Committee approved all studies. In vitro experiments VX2 cell lines cultured and were randomly assigned to four treatment groups, namely. Group A, phosphate-buffered saline (n = 6); group B, 5 μΜ Doxorubicin alone; hroup C, 42°C culture for 20 min (n = 6); and group D, 5 μΜ doxorubicin plus under 42°C culture for 20 min (n = 6). The viability and doxorubicin uptake of VX2 tumor cells line were assayed by flow cytometer and fluorescence microscopy at 24h after different treatment. Western blot was used to evaluate the Hsp70 expression. Tumor tissues were harvested from our Prestudy of rabbit liver VX2 tumor model. Fluorescence microscopy observed the distribution of doxorubicin, Hsp70 activity was analyzed by Western blot and Immunohistochemistry. P <0.05 was considered statistically significant. Radiofrequency hyperthermia-induced apoptosis and necrosis in VX2 cells in a mechanism of enhancing doxorubicin dose in cell and Hsp 70 expression. Fluorescence microscopy showed a further increase doxorubicin concentration in tumor cells and the penetration depth in tumor tissue. The western blot result showed Hsp70 expression in the combined group was significantly greater than in the control groups (mean ± SEM: 0.15 ± 0.03 vs. 0.64 ± 0.13 vs. 0.83 ± 0.10 vs. 1.28 ± 0.13, P <0.05). In the tumor tissue, immunohistochemistry staining results showed the significant increase of Hsp70-positive signaling was observed in RFH combined doxorubicin group than control group (P <0.01). Significantly increased of the tumor apoptosis and necrosis also found in the combined group with Ki-67 and TUNEL staining (P < .001). Radiofrequency hyperthermia mediate chemotherapy-induced VX2 cell killing regulated cell death mechanisms include enhance penetration of doxorubicin and HSP70 interacting at several points on apoptotic and immune signaling pathways, leads to inhibition of apoptosis of cell death at the HCC tumor ablation margin.

Establishment of Rabbit Liver VX2 Tumor Model Using Percutaneous Puncture Inoculation of Tumor Fragment Guided and Evaluated by Ultrasonography.

The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography. VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography. Conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) were performed 14 days after inoculation, and then the rabbits were sacrificed and pathologically examined. The success rate of inoculation was 100%. The average size of liver VX2 tumor was 1.7 cm×1.3 cm, CEUS of VX2 liver tumors showed the "rapid wash-in and wash-out" vascular pattern. There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A, k and A × k (P<0.05), which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma. Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor. And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.

Feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor.

BACKGROUNDHepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed.AIMTo investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor.METHODSIn this study, a rabbit liver VX2 tumor model was established. After laparotomy, under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis.RESULTSThe spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue.CONCLUSIONHyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.

Intravoxel Incoherent Motion Diffusion-weighted MR Imaging for Early Evaluation of the Effect of Radiofrequency Ablation in Rabbit Liver VX2 Tumors

This study aims to investigate the value of intravoxel incoherent motion (IVIM)-derived parameters for early evaluation of the efficiency of radiofrequency ablation (RFA) treatment for rabbit liver VX2 tumor. Eighteen rabbit liver VX2 tumor models were constructed, and computed tomography-guided RFA was performed. One day before and 7 days after RFA, 18 models underwent magnetic resonance imaging, including contrast-enhanced imaging and IVIM diffusion-weighted imaging with 16 b-factors (0-1000 s/mm2). Post-RFA liver tumors were segmented into viable tumor, inflammatory reaction, and ablation necrotic regions according to gross and histopathologic examinations. Parameters derived from IVIM were calculated. One-way analysis of variance and least significant difference test were used for comparisons among the three regions. The diagnostic performance of parameters was evaluated using receiver operating characteristic (ROC) analysis. ADCtotal, D, and f values were significantly lower in viable tumor than in inflammatory reaction regions (all P < .05), but D* showed no significant difference between the two regions. ADCtotal values of viable tumor regions were significantly lower than that of ablation necrotic regions (P = .007), but D* values of necrotic regions were significantly lower than that of viable tumor regions (P = .045). In ROC analysis, ADC showed the highest area under the ROC curve for differentiating inflammatory reaction from viable tumor region. ADCtotal, D, and f were valuable discriminating markers for differentiation between regions of viable tumor and inflammatory reaction in post-RFA tumor, especially ADCtotal outperformed the other two parameters with higher diagnostic performance.

Comparison of microvascular perfusion evaluation among IVIM-DWI, CT perfusion imaging and histological microvessel density in rabbit liver VX2 tumors

ObjectTo explore microcirculation features with intravoxel incoherent motion (IVIM) and to compare IVIM with CT perfusion imaging (CTPI) and microvessel density (MVD). Materials and methodsHepatic CTPI and IVIM were performed in 16 rabbit liver VX2 tumor models. Hepatic arterial perfusion (HAP), hepatic arterial perfusion index (HPI), Blood flow (BF), and blood volume (BV) from CTPI were measured. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) from IVIM were measured. MVD was counted with CD34 stain. The microcirculation features with IVIM were compared with CTPI parameters and MVD. ResultsStrong linear correlations were found between D value (0.89±0.21×10−3mm2/s) and HAP (15.83±6.97ml/min/100mg) (r=0.755, P=0.001) and between f value (12.64±6.66%) and BV (9.74±5.04ml/100mg) (r=0.693, P=0.004). Moderate linear correlations were observed between ADC (1.07±0.32×10−3mm2/s) and HAP (r=0.538, P=0.039), respectively; and between D value and MVD (9.31±2.57 vessels at 400×magnification) (r=0.509, P=0.044). No correlations were found between D* (119.90±37.67×10−3mm2/s) and HAP, HPI (68.34±12.91%), BF (4.95±2.16ml/min/100mg), BV. ConclusionIVIM parameters can characterize microcirculation to certain extent and separate it from pure water molecular diffusion. There is fair correlation between D or ADC value and CTPI parameters or MVD, but no correlation between D* or f value and CTPI parameters or MVD except f value and BV, which is still unclear and need further clinical studies to validate.

Total liver CT perfusion imaging for evaluation on rabbit liver VX2 tumor perfusion and comparative analysis through immunohistochemisty

To investigate the correlations among total liver CT perfusion parameters, unpaired arteries (UAs) and microvessel area (MVA) in a rabbit liver VX2 tumor model, and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging. Methods: Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation. Perfusion parameters included blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal liver perfusion (PVP), hepatic perfusion index (HPI) for the tumor rim and the surrounding liver tissue. After the examination, the UAs and MVA of tumor tissues were obtained by immunohistochemical staining. The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared. The correlations among perfusion parameters, UAs and MVA were analyzed. Results: There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group (P<0.05), but there was no significant difference between the perfusion parameters at the surrounding liver tissues of the experimental group and the control (P>0.05). There was positive correlation between UAs and MVA. UAs and MVA were positively correlated with BF, ALP and BV at the tumor rim. UAs and MVA were negatively correlated with PVP. HPI positively correlated with UAs, but it was not correlated with MVA. Conclusion: Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor, and to assess the degree of tumor angiogenesis.

Preliminary study on the relationship between the blood supply of rabbit liver VX2 tumor models and the HIFU

Objectives To explore the effects of the blood supply extent on the temperature of target site of tumor and volume of coagulation necrosis (V), and to provide experimental evidence for further precise control of dosage of high intensity focused ultrasound (HIFU) and improve the efficiency of HIFU in the treatment. Methods Twenty-four rabbit liver VX2 tumor models were established and were divided into four groups: 10 d group, 15 d group, 20 d group, no blood supply group (rabbits were put to death in the 10 d after the models were established). The same irradiation parameters of HIFU were used to irradiate the hepatic tumor tissue of every group, the real-time temperature of target site of tumor were measured, the software from temperature controller was used to plot the time-temperature curve (TTC), V was measured after HIFU. Residual tumor tissue was resected for pathological observation and microvascular density (MVD) determination. Results ⑴ Histopathological analysis showed that the extent of a tumor's blood supply followed the order 10 d group > 15 d group > 20 d group (P 0.05), Tmax, T1, and k1 between three groups with no blood supply group had statistical difference (P 15 d group > 20 d group > no blood supply group; T2: 10 d group < 15 d group < 20 d group < no blood supply group; ⑷V: 10 d group < 15 d group < 20 d group < no blood supply group. Conclusions The extent of a tumor's blood supply had a significant effect on the temperature-decrease phase but not on the temperature-increase phase during HIFU treatment. The more abundant blood supply of the tumor was, the faster heat abstraction after HIFU was; and the easier the tissue return to normal temperature, the smaller the volume of coagulation necrosis tissue were. Key words: Liver neoplasms, experimental/BS/TH; Ultrasound, high-intensity focused, transrectal; Disease models, animal

Effect of hepatic artery embolization on liver hypertrophy response in a rabbit liver VX2 tumor model

Portal vein embolization not only induces hypertrophy of the non-embolized liver, but also enhances tumor growth. The latter could be prevented by embolizing the hepatic arteries supplying the tumor-bearing liver segments. This study aimed to determine the effects of transcatheter arterial embolization (TAE) on tumor volume and liver regeneration in a rabbit VX2 tumor model. Twenty-three rabbits underwent subcapsular tumor implantation with a VX2 tumor. Two weeks after implantation, 18 rabbits were used for TAE experiments, 5 were for sham controls. Tumor response and liver regeneration response of the embolized cranial and non-embolized caudal liver lobes were assessed by CT volumetry, liver to body weight index, and the amount of proliferating hepatocytes. All super-selective arterial tumor embolization procedures were performed successfully. Despite embolization, the tumor volume increased after an initial steady state. The tumor volume after embolization was smaller than that of the sham group, but this difference was not significant. Massive necrosis of the tumor, however, was seen after embolization, without damage of the surrounding liver parenchyma. There was a significant atrophy response of the tumor bearing cranial lobe after super-selective arterial embolization of the tumor with a concomitant hypertrophy response of the non-embolized, caudal lobe. This regeneration response was confirmed histologically by a significantly higher number of proliferating hepatocytes on the Ki-67 stained slides. Super-selective, bland arterial coil embolization causes massive necrosis of the tumor, despite increase of volume on CT scan. Atrophy of the tumor bearing liver lobe is seen after arterial embolization of the tumor with a concomitant hypertrophy response of the non-embolized lobe, despite absence of histological damage of the tumor-surrounding liver parenchyma.

Dynamic characteristics of MR diffusion-weighted imaging in a rabbit liver VX-2 tumor model

To investigate prospectively dynamic characteristics of the apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) in a rabbit VX-2 tumor model. Forty New Zealand rabbits were included in the study, and 47 rabbit VX-2 tumor models were developed by direct and intrahepatic implantation after opening the abdominal cavities. DWI was carried out periodically and respectively on days 7, 14 and 21 after implantation. The VX-2 tumor samples were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their ADC values by analysis of variance (ANOVA) using SPSS12.0 software. The ADC values (mean ± SD) × 10(-3) mm(2)/s of 47 VX-2 tumors in the peripheral and central areas were 2.18 ± 0.29, 1.96 ± 0.33, 1.80 ± 0.35, 2.20 ± 0.29, 2.05 ± 0.30 and 1.96 ± 0.48, respectively, on days 7, 14 and 21 after implantation. ADC values of 47 VX-2 tumors in the area of the tumor periphery, center and normal parenchyma were higher when the b-value was 100 s/mm(2) than those when the b-value was 300 s/mm(2) (F = 17.964, p < 0.001; F = 13.986, p < 0.001; F = 128.681, p < 0.001). ADC values in the area of normal liver parenchyma were higher than those in the area of the VX-2 tumor periphery and center when the b-value was 100 or 300 s/mm(2). ADCs of viable tumor cells in VX-2 tumors were lower on DWI than those in the area of normal liver parenchyma around the tumor, and ADCs of dead tumor cells in VX-2 tumors were unequal, including high, equal and low values, but they were higher than in the area of normal liver parenchyma around tumors after dead tumor cells had been liquefied or had become cystic. ADC is correlated with the tumor histology and degree of malignancy, and DWI has potential value for dynamically monitoring tumors and evaluating the degree of malignancy and therapeutic effect.

Study on the dynamic characteristics and pathological mechanism of magnatic resonance diffusion weighted imaging after chemoembolizaiton in rabbit liver VX-2 tumor model

Objective To investigate its dynamic characteristics and pathological mechanism on magnatic resonance diffusion weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model.Methods Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity was opened.Forty VX-2 tumor models from them were divided into four groups.DWI was performed periodically and respectively for each group after chemoembolization.All VX-2 tumor samples of each group were studied by pathology.The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values.The statistical significance between different time groups,different area groups,or different b-value groups was calculated using SPSS 12.0 software.Results When b-value was 100 s/mm2,ADC values in the area of VX-2 tumor periphery,VX-2 tumor central,or normal liver parenchyma around tumor became gradually low in sixteen hours after chemoembolization,and were the lowest at sixteenth hour,and then they increased gradually from sixteenth hour to fourty-eighth hour after chemoembolization.The distinction of ADC between different time groups was significant,respectively ( F =7.325,P ＜ 0.01 ; F =2.496,P ＜ 0.05 ; F =6.856,P ＜0.01 ).Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor increased quickly in sixteen hours after chemoembolization; however,from sixteenth hour to forty-eighth hour,cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at first and then increased continually.Cellular necrosis in the area of VX-2 tumor periphery after chemoembolization was more significant than that before chemoembolization.The areas of dead cells in VX-2 tumors manifested low signal and high ADC value while the areas of viable cells manifested high signal and low ADC value.Conclusions DWI is able to detect and discriminate tumor necrotic areas from viable cellular areas before and after chemoembolization.ADC of normal liver parenchyma and VX-2 tumor are influenced by intracellular edema,tissue cellular death,and microcirculation disturbance after chemoembolization. Key words: Magnetic resonance imaging; Liver neoplasms,experimental/drug therapy; Liver neoplasms,experimental/pathology; Chemoembolization,therapeutic; Rabbits

Systemic administration of 3-bromopyruvate in treating disseminated aggressive lymphoma

The Warburg hypothesis states that aggressive cancers obtain much of their adenosine triphosphate (ATP) by metabolizing glucose directly to lactic acid. As a result of its high tumor selectivity, 3-bromopyruvic acid (3-BrPA), a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. We investigated the effect of 3-BrPA in a mouse model of aggressive metastatic lymphoma. Epstein-Barr-virus-infected human Raji lymphoma cells with lentivirally transfected green fluorescent protein and luciferase were incubated with RPMI/fetal bovine serum, and various concentrations of 3-BrPA were used to determine the LD50 in vitro. In total, 18 severely combined immunodeficient mice were injected with 1 million human Raji lymphoma cells via the tail vein. Using bioluminescent imaging, tumor growth was measured daily for 12 days to determine the tumor burden. At day 0 (start of treatment), the mice were randomized. Six mice received 10 mg/kg 3-BrPA i.p. daily for 7 days, 6 mice received 1 treatment at day 0, and 6 mice received the control buffer. Tumor growth was assessed daily from day 0 until day 7 using bioluminescent imaging. All data were normalized to acquisition time (luminescence/second; L/s). Body weight was measured daily to determine the toxicity of 3-BrPA. The LD50 for Raji lymphoma cells exposed to 3-BrPA in vitro was 11 μM with an extremely steep dose response curve. At day 0, tumor activity medians in the group with daily treatment was 2131 L/s (244-12,725), with a 1-day dose of 3095 L/s (523-9650) and in the nontreated control group, 2997 L/s (1521-6911). In mice treated with a daily dose of 10 mg/kg 3-BrPa for 7 days, a significant reduction in tumor activity was found during the whole treatment period compared with the control mice (P = 0.0043 at day 7). In mice with a single treatment at day 0, growth delay was only evident at day 2 (P = 0.0152 at day 2) but not for the rest of the observation period. The only manifestation of toxicity of the daily administration of 10 mg/kg 3-BrPA was a reduction in body weight. Body weight at day 0 was 17.22 g ± 0.84 g in the treatment group and 17.58 g ± 0.86 g in the control group. Body weight at day +6 was 15.02 g ± 2.04 g in the treated group and 19.4 g ± 0.63 g in the control group. 3-BrPA demonstrated a significant positive tumor response both in vitro and in vivo. This, to our knowledge, is the first report of the use of 3-BrPA in a systemic tumor model. Based on these data, 3-BrPA holds promise for treatment of systemic metastatic cancers.

3.0 T MR diffusion weighted imaging in the evaluation of radio-frequency ablation of the liver VX2 tumors

Objective To evaluate 3.0 T MR DWI techniques in detecting the lesions of pre and post-radiofrequency ablation of the rabbit liver VX2 tumors. Methods Twenty two New Zealand white rabbits were used in this experiment. Twenty tumor fragments were implanted into the livers of 20 rabbits respectively. Two normal rabbits were used as controls for radiofrequency ablation of the normal liver. 3.0 T MR DWI was performed 14 to 21 days after tumor implantation (mean, 17 days) in the tumor-bearing animals. Radiofrequency ablation was performed in the 18 tumor-bearing animals and in the two healthy animals. 3.0 T MRI and DWI were performed 7 to 10 days after radiofrequency ablation (mean, 8 days).Pathology was obtained immediately after the completion of post-radiofrequency ablation MR imaging. The MRI features and ADC values of pre- and post -radiofrequency ablation lesions in the liyers with VX2 tumors and normal rabbits were analyzed and correlation was made with histopathologic findings. Analysis of variance repeated measures were performed in analyzing the differences among the ADC values of different tissues with the same b value. Results All 20 rabbit liver models of VX2 tumors were constructed successfully. One rabbit died of anesthetic overdose, another one showed necrosis within the implanted tumor. All 18 untreated VX2 tumors had predominantly low or iso-signal intensity on T1 WI and high signal intensity on T2WI. All 18 VX2 tumors and 2 normal rabbits were treated by radiofrequency ablation successfully. Lesions treated by Radiofrequency ablation displayed low signal intensity on T1 WI, and high signal intensity on T2WI. Seven to 10 days after radiofrequency ablation, lesions varied from having low signal intensity to slightly increased signal intensity on T1 WI, with areas of mixed ( high, intermediate, and low) signal intensity. A peripheral rim of high signal intensity with varying thickness on T2WI correlated with granulation tissue, which exhibited intense enhancement on contrast-enhanced images. Areas of low to intermediate signal intensity within the lesion on T2WI corresponded to coagulation necrosis. The tumor tissue appeared as areas of peripheral nedularity, with intermediate to high signal intensity on T2-weighted images and DWI. The tumor specimen was gray, among the tumor tissue, there were hyperplastic vessels,and granulation tissue. When b value was 600 s/mm2 , the ADC value of viable tumor (9 cases), necrosis (18 cases), granulation tissue ( 18 cases), normal liver tissue ( 18 cases) were ( 1. 227 ±0. 140) × 10-3,(0. 702 ± 0. 050)×10-3, ( 1.918 ± 0.124) × 10-3, ( 1. 739 ± 0. 044 ) × 10-3 mm2/s, respectively, which were statistically significant (P ＜0. 01 ). When b =200,400,600,800,1000 s/mm2, the differences of ADC values among viable tumor, granulation tissue, necrosis,normal liver tissue were also statistically significant ( P ＜0. 01 ). Conclusion The rabbit liver VX2 tumor models and 3.0 T MR DWI are important tools in the basic and clinical researches of radiofrequency ablation. Key words: Liver neoplasms; Magnetic resonance imaging; Radiology,interventional

Correlation between MR diffusion weighted imaging with malignant degree of rabbit liver VX2 tumor models

To investigate the correlation between MR diffusion weighted imaging with cellularity and PCNA-LI of rabbit liver VX2 tumor models in different periods. 38 successful implanted rabbits were assigned randomly into 2 equal groups and were performed MR DWI in different periods (14 and 21 d) after implantation respectively. Specimens of all tumors were stained with HE and PCNA-LI after MR examination. (1) The ADC value (x 10(-3) mm2/s) in surrounding solid components of liver VX2 tumors in the group of 21 d was lower than that of the group of 14 d (0.77 +/- 0.19 vs 1.00 +/- 0.24, P = 0.007); (2) the cellularity and PCNA-LI in surrounding solid components of liver VX2 tumors in the group of 21 d were higher than those of the group of 14 d respectively (63% +/- 7% vs 43% +/- 10%, P = 0.011; 80% +/- 11% vs 56% +/- 8%, P = 0.008); (3) there were negative correlation between ADC value and cellularity, PCNA-LI of the solid components of the tumors (r = - 0.695, P = 0.000; r = -0. 698, P = 0.000). The cellularity may be the most important factor that affects ADC value in solid components of liver VX2 tumors. Since the degree of malignancy is closely connected with cellularity and PCNA labeling index, ADC value measurement may be a new method which could predict the degree of malignancies in vivo.

Effect of radio frequency ablation on vascular endothelial growth factor expression in rabbit liver VX2 tumor models

Effect of radio frequency ablation on vascular endothelial growth factor expression in rabbit liver VX2 tumor models

Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and Strept Avidin-Biotin Complex (SABC) immunohistochemical staining. The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNA and nm23 expression in the VX-2 tumor periphery first increased and then decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm(2), there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor periphery influenced the ADC. The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

Characteristics of liver on magnetic resonance diffusionweighted imaging: Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model. Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21st d. Ten VX-2 tumor samples were studied pathologically. The rate of lump detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (c2=32.61, P<0.001) on the 7th d after implantation and 95.8%, 54.3% and 82.9% (c2=21.50, P<0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21st d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually distinct and internal signals of tumor became progressively uneven. The manifestations of viable, necrotic and liquefied or cystic areas in VX-2 tumors on DWI are typical and DWI is of significant and potential values in clinical application in both the early detection and diagnosis of liver tumors.

Characteristics and pathological mechanism on magnetic resonance diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

To investigate dynamic characteristics and pathological mechanism of signal in rabbit VX-2 tumor model on diffusion-weighted imaging (DWI) after chemoembolization. Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity opened. Forty VX-2 tumor models from them were divided into four groups. DWI was performed periodically and respectively for each group after chemoembolization. All VX-2 tumor samples of each group were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance between different time groups, different area groups or different b-value groups was calculated by using SPSS12.0 software. Under b-value of 100 s/mm(2), ADC values were lowest at 16 h after chemoembolization in area of VX-2 tumor periphery, central, and normal liver parenchyma around tumor, but turned to increase with further elongation of chemoembolization treatment. The distinction of ADC between different time groups was significant respectively (F = 7.325, P < 0.001; F = 2.496, P < 0.048; F = 6.856, P < 0.001). Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor, increased quickly in sixteen h after chemoembolization but, from the 16th h to the 48th h, cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at, and then increased continually. After chemoembolization, Cellular necrosis in the area of VX-2 tumor periphery was more significantly high than that before chemoembolization. The areas of dead cells in VX-2 tumors manifested low signal and high ADC value, while the areas of viable cells manifested high signal and low ADC value. DWI is able to detect and differentiate tumor necrotic areas from viable cellular areas before and after chemoembolization. ADC of normal liver parenchyma and VX-2 tumor are influenced by intracellular edema, tissue cellular death and microcirculation disturbance after chemoembolization.