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

PURPOSE: To investigate prospectively dynamic characteristics of the apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) in a rabbit VX-2 tumor model. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

VEGF(165) expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro.

A short half-life and low levels of growth factors in an injured microenvironment necessitates the sustainable delivery of growth factors and stem cells to augment the regeneration of injured tissues. Our aim was to investigate the ability of VEGF(165) expressing bone marrow mesenchymal stem cells (BMMSCs) to differentiate into hepatocytes when cultured with hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in vitro. We isolated, cultured and identified rabbit BMMSCs, then electroporated the BMMSCs with VEGF(165)-pCMV6-AC-GFP plasmid. G418 was used to select transfected cells and the efficiency was up to 70%. The groups were then divided as follows: Group A was electroporated with pCMV6-AC-GFP plasmid + HGF + EGF and Group B was electroporated with VEGF(165)-pCMV6-AC-GFP plasmid +HGF + EGF. After 14 days, BMMSCs were induced into short spindle and polygonal cells. Alpha-fetoprotein (AFP) was positive and albumin (ALB) was negative in Group A, while both AFP and ALB were positive in group B on day 10. AFP and ALB in both groups were positive on day 20, but the quantity of AFP in group B decreased with prolonged time and was about 43.5% less than group A. The quantity of the ALB gene was increased with prolonged time in both groups. However, there was no significant difference between group A and B on day 10 and 20. Our results demonstrated that VEGF(165)-pCMV6-AC-GFP plasmid modified BMMSCs still had the ability to differentiate into hepatocytes. The VEGF(165) gene promoted BMMSCs to differentiate into hepatocyte-like cells under the induction of HGF and EGF, and reduced the differentiation time. These results have implications for cell therapies.

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

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 diffusion-weighted imaging: dynamic and image pathological investigation in rabbit liver VX-2 tumor model.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

AIM: To investigate dynamic characteristics and pathological mechanism of signal in rabbit VX-2 tumor model on diffusion-weighted imaging (DWI) after chemoembolization. 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 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. RESULTS: 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. CONCLUSION: 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.

[Subject diagnostic value of detecting a1pha-fetoprotein variants with a new microspincolumn method in hepatocellular carcinoma].

OBJECTIVE: To evaluate the usefulness of new microspincolumn method for the measurement of a1pha-fetoprotein variant AFP-L3 in differentiation of benign and malignant liver disease and the warming for liver cancer. METHODS: AFP-L3 was isolated by using microspincolumn coupled with lens culinaris agglutinin (LCA), AFP and AFP-L3 were determined with chemiluminescent immunoassay, the proportion of AFP-L3 levels AFP-L3(%) were calculated, and the relationship between the elevated AFP-L3(%) levels and benign and malignant liver disease was analyzed. RESULTS: The levels of AFP-L3(%) in serum of patients with hepatocellular carcinoma was significantly higher than those in the patients with other liver diseases (P < 0.001). Taking AFP-L3(%) >or= 10% as the diagnostic criteria, the sensitivity for diagnosis of liver cancer was 90.9%. CONCLUSION: Detection of AFP-L3 seemed to be of clinical value in diagnosis and differential diagnosis of hepatocellular carcinoma; it may be especially important for identifying patients with hepatocellular carcinoma whose a1pha-fetoprotein level is low.

MR diffusion-weighed imaging of rabbit liver.

AIM: To study the techniques of MR diffusion-weighed imaging (DWI) for normal rabbit liver. METHODS: After 15 normal New Zealand white rabbits and one New Zealand white rabbit implanted with VX-2 tumor were anesthetized with 3% soluble pentobarbitone, DWI was performed respectively for different b values, repetition times (TR) or thicknesses, when other parameters were the same and magnetic resonance imaging (MRI) was performed respectively, or with different field of views (FOV) or coil when other parameters were the same. The distinction between groups was analyzed by SPSS10.0 with apparent diffusion coefficient (ADC), quality index (QI) or signal-noise ratio (SNR). RESULTS: As b value increased, liver ADC, QI and SNR of DWI became smaller and simultaneously (F = 292.87, 156.1, 88.23, P<0.01). QI of DWI was high, when b value was 10, 50 or 100 respectively, but the distinction between them was insignificant; when b value was 800, QI and SNR of DWI were low. QI and SNR of DWI had no significant difference between TR = 4 000, 6 000 and 8 000. QI of DWI with 2 mm thickness was bigger than that with 5 mm thickness (t = 3.04, P<0.01), but SNR of DWI with 2 mm thickness was significantly smaller (t = -17.86, P<0.01). SNR of MRI with knee joint coil was obviously bigger than that with cranium coil (t = -5.77 (T1WI) or -4.02 (T2WI), P<0.01), but QI of MRI was smaller on the contrary (t = 7.10 (T1WI) or 3.97 (T2WI), P<0.01). When FOV was enlarged gradually, SNR of MRI increased (F = 85.81 (T1WI) or 221.96 (T2WI), P<0.01), but QI firstly increased, then decreased (F = 68.67 (T1WI) or 69.46 (T2WI), P<0.01) and QI of MRI was the biggest when FOV was 20 cm x 15 cm. CONCLUSION: The scanning technique is very important in DWI of rabbit liver and the overall quality of DWI with b (100 s/mm2), thickness (2 mm), cranium coils and FOV (20 cm x 15 cm) was best in our study, when other parameters were the same.

MR diffusion-weighted imaging of rabbit liver VX-2 tumor.

AIM: To investigate the implanting method of rabbit liver VX-2 tumor and its MR diffusion-weighted imaging (DWI) characteristics. METHODS: Thirty-five New Zealand rabbits were included in the study. VX-2 tumor was implanted subcutaneously in 14 rabbits and intrahepatically in 6 for pre-experiments. VX-2 tumor was implanted intrahepatically in 12 rabbits for experiment and three were used as the control group. DWI, T1- and T2-weighted of MRI were performed periodically in 15 rabbits for experiment before and after implantation. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance was calculated by analysis of variance (ANOVA) of the randomized block design using SPSS10.0 software. RESULTS: The successful rate of subcutaneous implantation of VX-2 tumor was 29% (4/14) while that of intrahepatic implantation of it was 33% (2/6) in the pre-experiment. The successful rate of intrahepatic implantation of VX-2 tumor in the experiment was 83% (10/12) and 15 tumors grew in 10 successfully implanted rabbits. The DWI signal of VX-2 tumor was high and became lower when the b value increased step by step. The signal of VX-2 tumor on the map of ADC was low. When the b value was 100 or 300 s/mm2, the ADC value of normal group and VX-2 tumor group was respectively 2.57+/-0.26, 1.73+/-0.31, 1.87+/-0.25 and 1.57+/-0.23 mm2/s. Their distinction was significant (F = 43.26, P<0.01), the tumor ADC value between b values 100 and 300 s/mm2 was significant (Tukey HSP, P<0.05) and the ADC value between VX-2 tumor and normal liver was also significant (Tukey HSP, P<0.01). VX-2 tumor developed quickly and metastasized early to all body, especially to the lung, liver, lymph nodes of mediastinum, etc. CONCLUSION: The DWI signal of rabbit VX-2 tumor has its characteristics on MR DWI and DWI plays an important role in diagnosing and discovering VX-2 tumor.