Abstract：
OBJECTIVE: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC).
METHODS: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors.
RESULTS: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = -0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = -0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02).
CONCLUSIONS: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment.
CONCLUSIONS: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy.
CONCLUSIONS: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment.
METHODS: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors.
RESULTS: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = -0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = -0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02).
CONCLUSIONS: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment.
CONCLUSIONS: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy.
CONCLUSIONS: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment.
摘要：
目的：为了研究组织扩散，刚度,切除肝细胞癌（HCC）的不同肿瘤微环境特征。
方法：72例患者被前瞻性纳入术前磁共振（MR）扩散加权成像和MR弹性成像检查。在肿瘤和肿瘤周围区域的中央三个切片上测量平均表观扩散系数（ADC）和刚度值。细胞密度,肿瘤基质比（TSR），富含淋巴细胞的HCC（LR-HCC），在切除的肿瘤中估计CD8+T细胞浸润。评估了MRI测量和主观病理评估的观察者之间的一致性。通过单变量分析筛选影响ADC和刚度的变量，然后用多元线性回归进行识别。在调整其他影响因素后，用线性回归评估探索的成像生物标志物与组织病理学特征之间的潜在关系。
结果：纳入72例患者（男/女：59/13，平均年龄：56±10.2岁）进行分析。关于MRI测量和组织病理学评估，读者之间的一致性良好或极好。未发现肿瘤ADC值与肿瘤硬度之间存在相关性。多变量线性回归证实，细胞密度是唯一与肿瘤ADC相关的因素（估计值=-0.03，p=0.006），肿瘤-基质比是与肿瘤硬度相关的唯一因素(估计值=-0.18,p=0.03)。在多元线性回归中调整纤维化分期（估计值=0.43，p<0.001）和年龄（估计值=0.04，p<0.001）后，肿瘤内CD8+T细胞浸润仍然是与肿瘤周围硬度相关的重要因素(估计值=0.63,p=0.02).
结论：肿瘤ADC超过肿瘤硬度作为细胞数量的生物标志物。肿瘤硬度与肿瘤基质比相关，肿瘤周围硬度可能是肿瘤内免疫微环境的成像生物标志物。
结论：组织硬度可能作为肝细胞癌肿瘤内免疫微环境的成像生物标志物，并有助于患者选择免疫治疗。
结论：表观扩散系数反映肝细胞癌的细胞性。肿瘤硬度反映了肝细胞癌的肿瘤基质比，并与肿瘤浸润淋巴细胞相关。肿瘤和肿瘤周围硬度可能作为肿瘤内免疫微环境的成像生物标志物。
方法：72例患者被前瞻性纳入术前磁共振（MR）扩散加权成像和MR弹性成像检查。在肿瘤和肿瘤周围区域的中央三个切片上测量平均表观扩散系数（ADC）和刚度值。细胞密度,肿瘤基质比（TSR），富含淋巴细胞的HCC（LR-HCC），在切除的肿瘤中估计CD8+T细胞浸润。评估了MRI测量和主观病理评估的观察者之间的一致性。通过单变量分析筛选影响ADC和刚度的变量，然后用多元线性回归进行识别。在调整其他影响因素后，用线性回归评估探索的成像生物标志物与组织病理学特征之间的潜在关系。
结果：纳入72例患者（男/女：59/13，平均年龄：56±10.2岁）进行分析。关于MRI测量和组织病理学评估，读者之间的一致性良好或极好。未发现肿瘤ADC值与肿瘤硬度之间存在相关性。多变量线性回归证实，细胞密度是唯一与肿瘤ADC相关的因素（估计值=-0.03，p=0.006），肿瘤-基质比是与肿瘤硬度相关的唯一因素(估计值=-0.18,p=0.03)。在多元线性回归中调整纤维化分期（估计值=0.43，p<0.001）和年龄（估计值=0.04，p<0.001）后，肿瘤内CD8+T细胞浸润仍然是与肿瘤周围硬度相关的重要因素(估计值=0.63,p=0.02).
结论：肿瘤ADC超过肿瘤硬度作为细胞数量的生物标志物。肿瘤硬度与肿瘤基质比相关，肿瘤周围硬度可能是肿瘤内免疫微环境的成像生物标志物。
结论：组织硬度可能作为肝细胞癌肿瘤内免疫微环境的成像生物标志物，并有助于患者选择免疫治疗。
结论：表观扩散系数反映肝细胞癌的细胞性。肿瘤硬度反映了肝细胞癌的肿瘤基质比，并与肿瘤浸润淋巴细胞相关。肿瘤和肿瘤周围硬度可能作为肿瘤内免疫微环境的成像生物标志物。
