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Diffusion-Weighted Magnetic Resonance Imaging of Focal Hepatic Nodules in an Experimental Hepatocellular Carcinoma Rat Model

Rationale and Objectives

We sought to investigate the value of diffusion-weighted MR imaging in evaluating focal hepatic nodules in an experimental hepatocellular carcinoma (HCC) rat model.

Materials and Methods

Forty rats with chemically induced primary hepatic nodules ranging pathologically from regenerative nodules (RNs) to dysplastic nodules (DNs) to HCC were examined with diffusion-weighted imaging. The apparent diffusion coefficient (ADC) values of hepatic nodular lesions were calculated. Tukey’s HSD post hoc test was used to compare the difference in ADC values between different hepatic nodular lesions.

Results

Eight RNs, 16 DNs, 7 well-differentiated HCCs (HCC well ), 11 moderately differentiated HCCs (HCC mod ), and 14 poorly differentiated HCCs (HCC poor ) were evaluated. There was no significant difference between RNs and DNs ( P > 0.05). Although the ADC values of HCC well were slightly lower than those of DNs, there was no significant difference between them ( P > 0.05). The ADC values of HCC mod and HCC poor were significantly higher ( P < 0.05) than those of other nodules, and no significant difference was seen between HCC mod and HCC poor ( P > 0.05).

Conclusion

Diffusion-weighted magnetic resonance imaging can be useful in characterizing focal hepatic nodular lesions, but ADC values cannot be used efficiently to distinguish HCC well from DNs.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, with highest incidences occurring in Africa, Southeast Asia, and China ( ). A cirrhotic liver is often the background from which HCC arises. One pathway to the development of HCC in patients with cirrhosis is a multistep carcinogenesis process from benign regenerative nodule (RN) to dysplastic nodule (DN) to a dysplastic nodule with microscopic foci of HCC, which may enlarge and replace the nodule giving rise to a small HCC, and finally to the overt HCC ( ). DNs are considered precancerous lesions of HCC ( ). Therefore, it is clinically important to detect DNs and HCC at an early stage for prompt surgical resection, transplantation, or local ablation therapy to ensure a better chance of survival.

Diffusion-weighted (DW) MRI is an imaging technique used to show microscopic motion in biologic tissues ( ). The apparent diffusion coefficient (ADC), a quantity calculated from the DW MR images, combines the effects of capillary perfusion and water diffusion in the extracellular extravascular space ( ). Thus, DW MRI is currently the only imaging method for assessing in vivo perfusion and diffusion simultaneously within the same organ ( ).

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Materials and methods

Animal Model

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MR Imaging

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Histology

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Image Analysis

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Statistical Analysis

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Results

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Table 1

ADC values of liver lesions calculated with various sets of b values

Liver lesions No. ADC (×10 −3 mm 2 /sec) of liver lesions calculated with various sets of b values Low b values ( b = 0, 600 sec/mm 2 ) High b values ( b = 0, 1,000 sec/mm 2 ) Cirrhotic liver 32 1.08 ± 0.09 0.94 ± 0.09 RNs 8 1.01 ± 0.13 0.90 ± 0.10 DNs 16 1.02 ± 0.11 0.91 ± 0.11 HCC well 7 0.98 ± 0.17 0.84 ± 0.12 HCC mod 11 1.21 ± 0.17 1.08 ± 0.14 HCC poor 14 1.24 ± 0.21 1.11 ± 0.18

Data are expressed as mean ± SD. RN, regenerative nodule; DN, dysplastic nodule; HCC well , well-differentiated HCC; HCC mod , moderately differentiated HCC; HCC poor , poorly differentiated HCC.

Figure 1, The ADC values of liver lesions calculated with b = 0, 600 sec/mm 2 ( A ) and b = 0, 1,000 sec/mm 2 ( B ). There was no significant difference among the cirrhotic liver, RNs, and DNs. Although the ADC value of HCC well was slightly lower than that of DNs, there was no significant difference between them. The ADC values of HCC mod and HCC poor were significantly higher than other hepatic nodules and no significant difference was seen between them. * P < .05. RN, regenerative nodules; DN, dysplastic nodules; HCC well , well-differentiated HCC; HCC mod , moderately differentiated HCC; HCC poor , poorly differentiated HCC.

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Figure 2, Well-differentiated HCC. ( A ) Transverse, coronal, and sagittal turbo spin-echo fat-saturated T2-weighted MR image shows a hyperintense tumor ( white arrow ). The tumor is hyperintense on DW MR images ( b = 600 sec/mm 2 , b = 1,000 sec/mm 2 ) ( B ) and hypointense on ADC map (calculated with b = 0, 1,000 sec/mm 2 ) ( C ). ( D ) Resected specimen of the tumor ( white arrow ). ( E ) Histologic examination results revealed a well-differentiated HCC. (Hematoxylin-eosin stain; original magnification, ×400.)

Figure 4, Poorly differentiated HCC and dysplastic nodule. ( A ) Transverse turbo spin-echo fat-saturated T2-weighted MR image shows the poorly differentiated HCC ( white arrow ) appears as a heterogeneous rounded area of hyperintensity located in the right lobe of the liver, and the DN ( white arrowhead ) appears as a hypointensity nodule in the left. ( B ) On DW MR images ( b = 600 sec/mm 2 , b = 1,000 sec/mm 2 ), a rim of high signal intensity representing viable tumor cells is clearly seen in the tumor ( white arrow ), reflecting intact cell membranes and restriction of water molecules. The area of necrosis at the central core of the tumor is identified as a black zone, reflecting increased diffusion of water molecules caused by breakdown of cell membranes. ( C ) On an ADC map (calculated with b = 0, 1,000 sec/mm 2 ), the area of tumor necrosis is a bright zone and a rim of low signal intensity representing the viable tumor is clearly seen. The DN ( white arrowhead ) appears isointense to the adjacent liver parenchyma on DW MR images and the ADC map. ( D ) Resected specimen reveals a nodular lesion ( white arrow ) about 5 mm in diameter containing darker areas ( black arrowhead ). At microscopic examination (not shown), the whole lesion was verified to be poorly differentiated HCC, while the darker area in it was necrotic. ( E ) Corresponding transverse sections from the liver depict the nodule ( white arrowhead ). ( F ) Histologic examination revealed the DN. (Hematoxylin-eosin stain; original magnification, ×200.)

Figure 3, Moderately differentiated HCC. ( A ) Transverse, coronal, and sagittal turbo spin-echo fat-saturated T2-weighted MR image shows a hyperintense nodule ( white arrow ) prominent in the liver. ( B ) The nodular lesion is hyperintense on DW MR images ( b = 600 sec/mm 2 , b = 1,000 sec/mm 2 ). ( C ) On the ADC map (calculated with b = 0, 1,000 sec/mm 2 ), the nodular lesion is slightly hypointense. ( D ) Corresponding transverse sections from the liver depict the nodule ( white arrow ). ( E ) The nodule was histologically proved to be moderately differentiated HCC. (Hematoxylin-eosin stain; original magnification, ×400.)

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Discussion

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Acknowledgments

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