Diffusion Weighted Imaging Of Rabbit Liver VX2 Tumor Models With Pathology In Different Periods

Objective To establish rabbit models of liver VX2 tumor and perform MR diffusion weighted imaging (DWI) examination with different b value in different growth periods, choose the optimal b value of DWI for characterization of tumors; to compare the distinction of signal intensities on DWI and their pathologic changes, explore the value of DWI for monitoring the growth characteristic of rabbit models of liver VX2 tumor; to compare the distinction of apparent diffusion coefficient (ADC) value and exponent apparent diffusion coefficient (eADC) value in surrounding solid components of liver VX2 tumor in different periods and their variation pattern, to analyze the correlation between ADC, eADC value and the celiularity, proliferating cell nuclear antigen (PCNA) labeling index in surrounding solid components in rabbit models of liver VX2 tumor, explore the pathologic basement on which solid components of liver VX2 tumor in different periods showed different ADC and eADC values.Materials and Methods Forty-four Zealand white rabbit were included in our study and VX2 tumor tissues were implanted into the left liver lobes after laparotomy. 38 successful implanted rabbits were assigned randomly into 2 equal groups and performed MR DWI in different periods (14d and 22d) after implantation respectively. MR scanning were performed on GE 1.5T Twin-Speed Infinity with Excite II scanner with 3 inch surface coil, single-shot spin-echo echo-planar diffusion-weighted imaging was performed with five different b values (200s/mm~2, 400s/mm~2, 600s/mm~2, 800s/mm~2, 1000s/mm~2), the diffusion sensitive gradient was applied to X, Y and Z directions at the same time. After DWI examination performed, ADC and eADC maps were obtained by postprocessing. Signal intensities of DWI, the values of ADC and eADC with different b value were measured in surrounding solid components in rabbit models of liver VX2 tumor in different periods respectively. Histological specimens of livers of all rabbits were sliced according to the direction of MR scanning rightly after MR examination and stained with hematoxylin, eosin and PCNA. Celiularity and PCNA labeling index of each specimen were measured in CMIAS (colored multifunction imaging analyzing system). The ratios of the total area of tumor cell nuclei to the area of sample field except for cell nuclei (including cytoplasm and extracellular space) were calculated in each specimen. The ratios of the PCNA stained positive tumor cell nuclei to the total tumor cell nuclei were measured in each specimen. The mean value of five visual fields was regarded as the cellularity and PCNA labeling index respectively, expressed by percentage. The following data were analyzed: 1. To observe the changes in tumor volume, tumor doubling time and signal intensities of T1WI,T2WI and DWI. 2. To analysis signal intensities ratio of tumor to liver (SIR), signal noise ratio (SNR) and contrast noise ratio of tumor to liver (CNR), evaluate imaging quality of DWI with different b value, choose the optimal b value. 3. To observe and analysis the signal intensities of DWI, ADC and eADC maps and their differences in different periods, and contrast with pathologic changes respectively. 4. To analysis and compare the distinction of ADC value and eADC value in surrounding solid components in rabbit models of liver VX2 tumor in different periods. 5. To analysis the correlation between ADC value, eADC value in surrounding solid components and cellularity, PCNA labeling index in different periods.Results 1. The successful rate of implantation method of VX2 tumor tissues implanted into the left liver lobe of rabbits after laparotomy was 86%. Each tumor was solitary. Tumor volumes were enlarged greatly on 22d compared with 14d. The mean volume were 1.76cm~3 and 0.32cm~3 repectively, the doubling time of two groups was 3.2d. 2. On MR scanning, all tumors in different growth periods showed slightly long T1 and slightly long T2 signal intensities with clear margin. Four tumors on 22d demonstrated patchly long T2 signal intensity in their central part. 3. All tumors showed obviously high signal intensity on DWI in different b value. 4. On DWI, the SIR of tumors increased gradually with b value increasing, the SNR and CNR decreased gradually with b value increasing, however, we could still recognize the lesions and calculate the ADC and eADC values in surrounding solid components in rabbit models of liver VX2 tumor with b value of 1000s/mm~2. 5. On ADC and eADC maps, all tumors in the group of 14d showed homogeneously high/low signal intensity. According to pathology, all tumor of this group demonstrated well distributed texture without cystic necrosis. 6. The ADC values in surrounding solid components of liver VX2 tumor decreased gradually with b value increasing in each group. The eADC values increased gradually with b value increasing in each group. 7. The ADC values with different b value in surrounding solid components of liver VX2 tumor in the group of 22d decreased compared with the group of 14d. The eADC values with different b value, cellularity and PCNA labeling index in the group of 22d increased compared with the group of 14d. With different b values, there were negative correlation between ADC value of surrounding solid components of and cellularity, PCNA labeling index, especially with b value of 1000s/mm~2. There was positive correlation between eADC value and cellularity, PCNA labeling index, especially with b value of 1000s/mm~2.Conclusions 1. The successful rate is much higher to establish the models of VX2 hepatic tumor by implanting tumor tissues into the liver after laparotomy. The characteristic of rabbit models of liver VX2 tumor is reproduction easily, growth rapidly, and appearing cystic necrosis easily. 2. The optimal b value in DWI examination is 1000s/mm~2 in present study. 3. ADC and eADC map could demonstrate the cystic and necrotic areas with typical imaging features in early time. They can early monitor the cystic necrosis areas in rabbit models of liver VX2 tumor, DWI plays an important value in dynamic detection of genesis and development of the tumor and the growth characteristic. DWI is helpful complement for conventional MR examination. 4. With the increasing of implantation time, the ADC values of the solid components of VX2 tumor decreased, and the eADC values increased. 5. Tumor cellularity is one of the important factors that affecting ADC and eADC values in solid components. Since the degree of malignancy is closely connected with cellularity and PCNA labeling index, measurement of ADC or eADC values may be a new method which could predict the degree of malignancy and pathology grading in vivo.