From the Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX (R.T., A.C.C., M.W., C.D., R.A.); Department of Diagnostic and Interventional Radiology, Nara Medical University, Nara, Japan (R.T., T.T., H.N.); Cardiology Division, Department of Internal Medicine, UT Health Science Center at Houston, Houston, TX (A.M.Z.); Siemens Healthineers AG, Erlangen, Germany (G.C.); and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, (C.B.P.).
Invest Radiol. 2023 Dec 1;58(12):894-902. doi: 10.1097/RLI.0000000000001001. Epub 2023 Jul 5.
Extracellular matrix stiffness represents a barrier to effective local and systemic drug delivery. Increasing stiffness disrupts newly formed vessel architecture and integrity, leading to tumor-like vasculature. The resulting vascular phenotypes are manifested through different cross-sectional imaging features. Contrast-enhanced studies can help elucidate the interplay between liver tumor stiffness and different vascular phenotypes.
This study aims to correlate extracellular matrix stiffness, dynamic contrast-enhanced computed tomography, and dynamic contrast-enhancement ultrasound imaging features of 2 rat hepatocellular carcinoma tumor models.
Buffalo-McA-RH7777 and Sprague Dawley (SD)-N1S1 tumor models were used to evaluate tumor stiffness by 2-dimensional shear wave elastography, along with tumor perfusion by dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography. Atomic force microscopy was used to calculate tumor stiffness at a submicron scale. Computer-aided image analyses were performed to evaluate tumor necrosis, as well as the percentage, distribution, and thickness of CD34+ blood vessels.
Distinct tissue signatures between models were observed according to the distribution of the stiffness values by 2-dimensional shear wave elastography and atomic force microscopy ( P < 0.05). Higher stiffness values were attributed to SD-N1S1 tumors, also associated with a scant microvascular network ( P ≤ 0.001). Opposite results were observed in the Buffalo-McA-RH7777 model, exhibiting lower stiffness values and richer tumor vasculature with predominantly peripheral distribution ( P = 0.03). Consistent with these findings, tumor enhancement was significantly greater in the Buffalo-McA-RH7777 tumor model than in the SD-N1S1 on both dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography ( P < 0.005). A statistically significant positive correlation was observed between tumor perfusion on dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography in terms of the total area under the curve and % microvessel tumor coverage ( P < 0.05).
The stiffness signatures translated into different tumor vascular phenotypes. Two-dimensional shear wave elastography and dynamic contrast-enhanced ultrasonography adequately depicted different stromal patterns, which resulted in unique imaging perfusion parameters with significantly greater contrast enhancement observed in softer tumors.
细胞外基质硬度是有效局部和全身药物输送的障碍。硬度的增加会破坏新形成的血管结构和完整性，导致类似于肿瘤的血管。由此产生的血管表型通过不同的横截面成像特征表现出来。对比增强研究可以帮助阐明肝肿瘤硬度与不同血管表型之间的相互作用。
本研究旨在对 2 种大鼠肝癌肿瘤模型的细胞外基质硬度、动态对比增强 CT 和动态对比增强超声成像特征进行相关性分析。
使用 Buffalo-McA-RH7777 和 Sprague Dawley（SD）-N1S1 肿瘤模型通过二维剪切波弹性成像评估肿瘤硬度，同时通过动态对比增强超声和对比增强 CT 评估肿瘤灌注。原子力显微镜用于计算亚微米级的肿瘤硬度。计算机辅助图像分析用于评估肿瘤坏死以及 CD34+血管的百分比、分布和厚度。
根据二维剪切波弹性成像和原子力显微镜的硬度值分布，观察到两种模型之间存在明显的组织特征（P<0.05）。SD-N1S1 肿瘤的硬度值较高，微血管网络也较少（P≤0.001）。Buffalo-McA-RH7777 模型则相反，硬度值较低，肿瘤血管丰富，主要分布在边缘（P=0.03）。这些发现与超声和 CT 增强一致，Buffalo-McA-RH7777 肿瘤模型的肿瘤增强明显大于 SD-N1S1 肿瘤模型（P<0.005）。超声和 CT 动态对比增强的肿瘤灌注的总曲线下面积和微血管肿瘤覆盖率的百分比之间存在显著的正相关（P<0.05）。
硬度特征转化为不同的肿瘤血管表型。二维剪切波弹性成像和动态对比增强超声能够充分描述不同的基质模式，从而产生独特的成像灌注参数，在较软的肿瘤中观察到显著更高的对比度增强。
