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扩散加权磁共振成像衍生的表观扩散系数值反映了子宫颈癌患者源肿瘤异种移植模型中的I型胶原蛋白含量。

Diffusion-weighted MRI-derived ADC values reflect collagen I content in PDX models of uterine cervical cancer.

作者信息

Hauge Anette, Wegner Catherine S, Gaustad Jon-Vidar, Simonsen Trude G, Andersen Lise Mari K, Rofstad Einar K

机构信息

Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

出版信息

Oncotarget. 2017 Nov 11;8(62):105682-105691. doi: 10.18632/oncotarget.22388. eCollection 2017 Dec 1.

Abstract

Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (DW-MRI) are known to reflect the cellular environment of biological tissues. However, emerging evidence accentuates the influence of stromal elements on ADC values. The current study sought to elucidate whether a correlation exists between ADC and the fraction of collagen I-positive tissue across different tumor models of uterine cervical cancer. Early and late generation tumors of four patient-derived xenograft (PDX) models of squamous cell carcinoma (BK-12, ED-15, HL-16, and LA-19) were included. DW-MRI was performed with diffusion encoding constants () of 200, 400, 700, and 1000 s/mm and diffusion gradient sensitization in three orthogonal directions. The fraction of collagen I-positive connective tissue was determined by immunohistochemistry. Mono-exponential decay curves, from which the ADC value of tumor voxels was calculated, yielded good fits to the diffusion data. A significant inverse correlation was detected between median tumor ADC and collagen I fraction across the four PDX models, indicating that collagen fibers in the extracellular space have the ability to inhibit the movement of water molecules in these xenografts. The results encourage further exploration of DW-MRI as a non-invasive imaging method for characterizing the stromal microenvironment of tumors.

摘要

已知从扩散加权磁共振成像(DW-MRI)得出的表观扩散系数(ADC)值可反映生物组织的细胞环境。然而,新出现的证据强调了基质成分对ADC值的影响。本研究旨在阐明在不同的子宫颈癌肿瘤模型中,ADC与I型胶原阳性组织比例之间是否存在相关性。纳入了四个来源于患者的鳞状细胞癌异种移植(PDX)模型(BK-12、ED-15、HL-16和LA-19)的早期和晚期肿瘤。DW-MRI在三个正交方向上进行,扩散编码常数()为200、400、700和1000 s/mm²,以及扩散梯度敏感化。通过免疫组织化学确定I型胶原阳性结缔组织的比例。从单指数衰减曲线计算肿瘤体素的ADC值,该曲线对扩散数据拟合良好。在四个PDX模型中,检测到肿瘤中位ADC与I型胶原比例之间存在显著的负相关,表明细胞外空间中的胶原纤维能够抑制这些异种移植中水分子的移动。这些结果鼓励进一步探索将DW-MRI作为一种用于表征肿瘤基质微环境的非侵入性成像方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da19/5739670/d29d8486c2c6/oncotarget-08-105682-g001.jpg

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