Objective: To explore the angiogenesis and its maturation of hepatocellular carcinoma (HCC) and its correlation with deoxyhemoglobin parameters R2 * and T2 * values and the lesion/muscle R2*, T2 * ratio by using noninvasive magnetic resonance imaging (MRI).
Methods: T2 *, R2 * values and the lesion/muscle R2 *, T2 * ratio in tumor periphery and center were calculated via series T2 * images in a total of 31 patients with surgically and pathologically confirmed HCC. After surgery, all sections were obtained from the specimen periphery in accordance with the MR analyzed areas. Continuous slices of each lesion were stained with hematoxylin-eosin (HE), and immunohistochemical staining was performed in vascular endothelial growth factor (VEGF), Flk-1, proliferating cell nuclear antigen (PCNA), CD34, and alpha smooth muscle actin (SMA). The expressions of VEGF, Flk-1, and PCNA index (PI) were evaluated. According to CD34 and SMA, some vascular parameters, including number, mean vessel area, total vessel area, circumference, diameter, distance between adjacent vessels, and variety index of microvessel and mature vessel, were calculated with a computed analysis system. The amounts of arterioles and veinlets, mature vessel index, and mean perfused fraction (mPF) were also recorded. All vessel parameters were compared with the calculated values of MRI.
Results: R2 * value or lesion/muscle R2 * ratio decreased and T2 * value or the lesion/muscle T2 * ratio increased in HCC when compared with hepatic parenchyma (P < 0.05); however, those values between lesion periphery and center and among different pathological grades were not significantly different (P > 0.05). T2 * value and the lesion/muscle T2 * ratio significantly decreased when the expression of VEGF was positive (P < 0.05). T2 * value was negatively correlated with microvessel amount (P = 0.047, r = - 0.639), while T2 * value and the lesion/muscle T2 * ratio were positively correlated with mPF (P = 0.040, r = 0.655; P = 0.048, r = 0.40, respectively). R2 * value was also positively correlated with mean area (P = 0.028, r = 0.688), total area (P = 0.021, r = 0.712) or circumference (P = 0.037, r = 0.663) of microvessel, and negatively correlated with mPF (P = 0.024, r = - 0.702). Meanwhile, the lesion/muscle R2 * ratio was positively correlated with mean area (P = 0.043, r = 0.647) and circumference (P = 0.026, r = 0.694) of microvessels.
Conclusion: R2 * or T2 * value may be influenced by the variation of deoxyhemoglobin caused by the heterogeneity of angiogenesis.