Noninvasive Quantification of Solid Tumor Microstructure Using VERDICT MRI

Noninvasive Quantification of Solid Tumor Microstructure Using VERDICT MRI
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DOI:
10.1158/0008-5472.can-13-2511
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发表时间:
2014-04-01
期刊:
影响因子:
11.2
通讯作者:
Alexander, Daniel C.
Alexander, Daniel C.
中科院分区:
医学1区
文献类型:
--
作者:
Panagiotaki, Eletheria;Walker-Samuel, Simon;Alexander, Daniel C.

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需要可用于肿瘤病理生理学和药物功效的无创成像的生物标志物。通过使用内源性水,扩散加权 MRI (DW-MRI) 可用于探测局部组织结构和结构。然而,大多数癌症组织的 DW-MRI 研究都依赖于简单化的数学模型,例如表观扩散系数 (ADC) 或体素内不相干运动 (IVIM) 模型,这些模型对模型参数估计与底层组织微观结构的关系产生模棱两可的结果。在这里,我们提出了一种称为 VERDICT(肿瘤细胞计数的血管、细胞外和限制扩散)的新技术,用于量化和绘制体内肿瘤的组织学特征。 VERDICT 将 DW-MRI 与肿瘤组织的数学模型结合起来,以获取细胞大小、血管体积分数、细胞内和细胞外体积分数以及与血流相关的伪扩散率等特征。为了说明 VERDICT,我们使用了两种具有不同细胞和血管表型的结直肠癌肿瘤异种移植模型。我们的实验可视化了每个模型组织微观结构的已知差异,以及细胞毒性药物吉西他滨给药导致的细胞体积显着减少,反映了细胞凋亡体积的减少。相比之下,标准 ADC 和 IVIM 模型未能检测到这些差异。我们的结果说明了 VERDICT 在癌症成像方面的卓越功能,将其确立为一种监测和分层治疗反应的非侵入性方法。 (C)2014 AACR。
There is a need for biomarkers that are useful for noninvasive imaging of tumor pathophysiology and drug efficacy. Through its use of endogenous water, diffusion-weighted MRI (DW-MRI) can be used to probe local tissue architecture and structure. However, most DW-MRI studies of cancer tissues have relied on simplistic mathematical models, such as apparent diffusion coefficient (ADC) or intravoxel incoherent motion (IVIM) models, which produce equivocal results on the relation of the model parameter estimate with the underlying tissue microstructure. Here, we present a novel technique called VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) to quantify and map histologic features of tumors in vivo. VERDICT couples DW-MRI to a mathematical model of tumor tissue to access features such as cell size, vascular volume fraction, intra-and extracellular volume fractions, and pseudo-diffusivity associated with blood flow. To illustrate VERDICT, we used two tumor xenograft models of colorectal cancer with different cellular and vascular phenotypes. Our experiments visualized known differences in the tissue microstructure of each model and the significant decrease in cell volume resulting from administration of the cytotoxic drug gemcitabine, reflecting the apoptotic volume decrease. In contrast, the standard ADC and IVIM models failed to detect either of these differences. Our results illustrate the superior features of VERDICT for cancer imaging, establishing it as a noninvasive method to monitor and stratify treatment responses. (C)2014 AACR.