<br>多 b 值 DWI 评估蟾蜍林加索拉非尼在原位 HCC 模型中的协同抗增殖和抗异质性作用,European Radiology Experimental

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多 b 值 DWI 评估蟾蜍林加索拉非尼在原位 HCC 模型中的协同抗增殖和抗异质性作用
European Radiology Experimental ( IF 3.7 ) Pub Date : 2024-03-12 , DOI: 10.1186/s41747-024-00448-y
Ran Guo ₁ , Fang Lu ₂ , Jiang Lin _{3,

4} , Caixia Fu ₅ , Mengxiao Liu ₆ , Shuohui Yang ₁

Affiliation

背景

具有不同后处理模型的多b值扩散加权成像（DWI）可以评估肝细胞癌（HCC）增殖、空间异质性和治疗策略的可行性。我们通过使用体素不相干运动（IVIM）、扩散峰度成像（DKI）、拉伸指数模型（SEM）和分数阶微积分（FROC）模型评估了蟾蜍林+索拉非尼在原位HCC-LM3异种移植裸鼠中的协同作用。

方法

将24只原位HCC-LM3异种移植小鼠分为蟾蜍灵+索拉非尼治疗组、蟾蜍灵+索拉非尼治疗组和对照组。治疗3周后使用3-T扫描仪进行多b值DWI，以获得真扩散系数D _t 、伪扩散系数D _p 、灌注分数f 、平均扩散率（MD）、平均峰度（MK）、分布扩散系数 (DDC)、异质性指数α 、扩散系数 D、分数阶参数β和微观结构量μ 。评估坏死分数（NF）、苏木精-伊红染色的标准差（SD）和抗CD31染色的微血管密度（MVD）。分析 DWI 参数与组织病理学结果的相关性，并比较四组之间的测量结果。

结果

在最后 22 只小鼠中， f与 MVD 呈正相关（ r = 0.679， p = 0.001）。观察到 MK ( r = 0.677)、 α ( r = -0.696) 和β ( r = -0.639) 与 SD 具有显着良好的相关性（所有p < 0.010）。蟾蜍林+索拉非尼组的f 、MK、MVD和SD显着低于对照组，而MD、 α 、 β和NF则高于对照组（均p < 0.050）。

结论

通过 IVIM、DKI、SEM 和 FROC 评估，发现蟾蜍林+索拉非尼可抑制 HCC-LM3 模型中的肿瘤增殖和血管生成，并降低空间异质性。

关键点

• 蟾蜍灵加索拉非尼组合可能会提高 HCC 治疗的有效性。

• 多b值DWI 描述了HCC 增殖、血管生成和空间异质性。

• 多b值DWI 可能是评估HCC 治疗效果的无创方法。

图解摘要

"点击查看英文标题和摘要"

Multi-b-value DWI to evaluate the synergistic antiproliferation and anti-heterogeneity effects of bufalin plus sorafenib in an orthotopic HCC model

Background

Multi-b-value diffusion-weighted imaging (DWI) with different postprocessing models allows for evaluating hepatocellular carcinoma (HCC) proliferation, spatial heterogeneity, and feasibility of treatment strategies. We assessed synergistic effects of bufalin+sorafenib in orthotopic HCC-LM3 xenograft nude mice by using intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), a stretched exponential model (SEM), and a fractional-order calculus (FROC) model.

Methods

Twenty-four orthotopic HCC-LM3 xenograft mice were divided into bufalin+sorafenib, bufalin, sorafenib treatment groups, and a control group. Multi-b-value DWI was performed using a 3-T scanner after 3 weeks’ treatment to obtain true diffusion coefficient D_t, pseudo-diffusion coefficient D_p, perfusion fraction f, mean diffusivity (MD), mean kurtosis (MK), distributed diffusion coefficient (DDC), heterogeneity index α, diffusion coefficient D, fractional order parameter β, and microstructural quantity μ. Necrotic fraction (NF), standard deviation (SD) of hematoxylin-eosin staining, and microvessel density (MVD) of anti-CD31 staining were evaluated. Correlations of DWI parameters with histopathological results were analyzed, and measurements were compared among four groups.

Results

In the final 22 mice, f positively correlated with MVD (r = 0.679, p = 0.001). Significantly good correlations of MK (r = 0.677), α (r = -0.696), and β (r= -0.639) with SD were observed (all p < 0.010). f, MK, MVD, and SD were much lower, while MD, α, β, and NF were higher in bufalin plus sorafenib group than control group (all p < 0.050).

Conclusion

Evaluated by IVIM, DKI, SEM, and FROC, bufalin+sorafenib was found to inhibit tumor proliferation and angiogenesis and reduce spatial heterogeneity in HCC-LM3 models.