Department of ultrasound, The First Medical Centre, Chinese PLA General Hospital, No. 28 of Fuxing Road, Haidian District, Beijing, 100853, China.
BMC Gastroenterol. 2024 Nov 23;24(1):424. doi: 10.1186/s12876-024-03523-1.
Hypoxia is a characteristic of solid tumors, but whether significant hypoxia exists in the hepatocellular carcinoma remains unclear. This animal study aims to explore the value of dynamic contrast-enhanced ultrasound (CEUS) quantitative parameters to evaluate the oxygen status in two rat hepatoma models.
N1S1 and McA-RH7777 S-D rat orthotopic hepatoma models were established. Once the tumors reached a diameter of 10-15 mm, CEUS and oxygen partial pressure (pO2) polarography were performed. Immunohistochemical staining for HIF-1α and pimonidazole was conducted after euthanizing the rats. Correlation between quantitative CEUS parameters, pO and the immunohistochemical integrated optical density (IOD) was analyzed to assess the predictive ability of CEUS quantitative parameters for the tissue oxygen environment.
Eleven N1S1 models and ten McA-RH7777 models were established successfully. There was no significant difference in pO (35.5 mmHg vs 32.2 mmHg, P = 0.917), IOD of HIF-1α (13.4 vs 20.0, P = 0.159) and pimonidazole (0.70 vs 1.30, P = 0.926) between the tumor and the peritumoral liver tissue. The pO values were correlated with CEUS quantitative parameters including mean time-intensity curves (mTIC) (P = 0.003), peak intensity (PKI) (P = 0.010), area under the curve (AUC) (P = 0.009), area under the wash-in curve (WiAUC) (P = 0.006), and arrival time (AT) (P = 0.033). The IOD of HIF-1α correlated with AUC (P = 0.022), WiAUC (P = 0.009), ascending slope (AS) (P = 0.044), and falling time (FT) (P = 0.009). Multiple linear regression indicated that the "short AT" was an independent protective factor for hypoxia (β = -2.347, 95% CI: -4.948, -0.394, P = 0.022), and CEUS had the ability to predict the tumor pO (P = 0.003).
No evidence of significant hypoxia was identified in two rat orthotopic hepatoma models. Quantitative CEUS parameters correlated with the oxygen status of the tumor, which could be utilized to predict the tumor tissue pO.
缺氧是实体瘤的一个特征，但肝癌中是否存在显著缺氧仍不清楚。本动物研究旨在探讨动态对比增强超声（CEUS）定量参数评估两种大鼠肝癌模型氧状态的价值。
建立 N1S1 和 McA-RH7777 S-D 大鼠原位肝癌模型。一旦肿瘤直径达到 10-15mm，进行 CEUS 和氧分压（pO2）极谱法检查。处死大鼠后进行 HIF-1α 和 pimonidazole 的免疫组织化学染色。分析定量 CEUS 参数、pO2 和免疫组化积分光密度（IOD）之间的相关性，以评估 CEUS 定量参数对组织氧环境的预测能力。
成功建立了 11 个 N1S1 模型和 10 个 McA-RH7777 模型。肿瘤与肿瘤周围肝组织之间的 pO2 值（35.5mmHg 与 32.2mmHg，P=0.917）、HIF-1α 的 IOD（13.4 与 20.0，P=0.159）和 pimonidazole（0.70 与 1.30，P=0.926）无显著差异。pO2 值与 CEUS 定量参数相关，包括平均时间强度曲线（mTIC）（P=0.003）、峰值强度（PKI）（P=0.010）、曲线下面积（AUC）（P=0.009）、曲线上升下面积（WiAUC）（P=0.006）和到达时间（AT）（P=0.033）。HIF-1α 的 IOD 与 AUC（P=0.022）、WiAUC（P=0.009）、上升斜率（AS）（P=0.044）和下降时间（FT）（P=0.009）相关。多元线性回归表明，“短 AT”是缺氧的独立保护因素（β=-2.347，95%CI：-4.948，-0.394，P=0.022），CEUS 具有预测肿瘤 pO2 的能力（P=0.003）。
在两种大鼠原位肝癌模型中未发现明显缺氧。定量 CEUS 参数与肿瘤的氧状态相关，可用于预测肿瘤组织的 pO2。
