Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.
Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.
复制标题
DOI：
10.1158/1078-0432.ccr-18-0033
复制
发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Kersemans V
中科院分区：
文献类型：
--
作者：
Kannan P;Kretzschmar WW;Winter H;Warren D;Bates R;Allen PD;Syed N;Irving B;Papiez BW;Kaeppler J;Markelc B;Kinchesh P;Gilchrist S;Smart S;Schnabel JA;Maughan T;Harris AL;Muschel RJ;Partridge M;Sharma RA;Kersemans V
肿瘤血管影响肿瘤的生长和对治疗的反应。使用动态对比增强MRI（DCE-MRI）对体内血管变化进行成像已显示出指导临床治疗决策的潜力。然而，血管功能的定量MR成像生物标志物尚未被广泛采用，部分原因是它们与血管结构变化的关系仍不清楚。我们的目的是阐明在体血管功能和形态之间的关系。使用DCE-MRI和计算机断层扫描（CT）对具有不同血管化水平的未经治疗的临床前肿瘤进行连续成像。使用线性模型评估MR的功能参数（iAUC、Ktranss和BATfrac）与CT的结构参数（血管容积、半径和迂曲度）之间的关系。然后对用抗VEGFR 2抗体治疗的肿瘤进行成像，以确定抗血管生成治疗是否改变了这些关系。最后，在10例结直肠癌肝转移患者中测量了功能-结构关系。功能参数iAUC和Ktranss主要反映未经治疗的临床前肿瘤的血管体积。这种关系在空间上和肿瘤血管分布上各不相同，并且通过抗血管生成治疗而改变。在人肝转移瘤中，所有三个结构参数均与iAUC和Ktranss线性相关。对于iAUC，结构参数也改变了彼此的影响。我们的研究结果表明，血管功能的MR成像生物标志物与肿瘤血管的结构变化有关，抗血管生成治疗可以影响这种联系。我们的工作还证明了MR生物标志物在体内的3D功能-结构验证的可行性，以提高其生物学解释和临床实用性。
Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology in vivo. Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and computed tomography (CT). Relationships between functional parameters from MR (iAUC, Ktrans, and BATfrac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether anti-angiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in ten patients with liver metastases from colorectal cancer. Functional parameters iAUC and Ktrans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by anti-angiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with iAUC and Ktrans. For iAUC, structural parameters also modified each other’s effect. Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels, and that anti-angiogenic therapy can affect this link. Our work also demonstrates the feasibility of 3D functional-structural validation of MR biomarkers in vivo to improve their biological interpretation and clinical utility.