Jiang Xiaoyu, Xu Junzhong, Gore John C
Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee.
Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee.
Adv Radiat Oncol. 2018 Nov 20;4(2):367-376. doi: 10.1016/j.adro.2018.11.003. eCollection 2019 Apr-Jun.
This study aims to test the ability of quantitative temporal diffusion spectroscopy (qTDS) to assess cellular changes associated with radiation-induced cell death in a rat glioma model.
Tumor response to a single fraction of 20 Gy of x-ray radiation was investigated in a rat glioma (9L) model. Tumor response was monitored longitudinally at postinoculation days 21, 23, and 25, using a specific implementation of qTDS with acronym IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion), as well as conventional diffusion and high-resolution anatomic imaging. IMPULSED method combines diffusion-weighted signals acquired over a range of diffusion times that are then analyzed and interpreted using a theoretical model of water diffusion in tissues, which generates parametric maps depicting cellular and subcellular structural information on a voxel-wise basis. Results from different metrics were compared statistically.
A single dose of 20 Gy x-ray radiation significantly prolonged survival of 9L-bearing rats. The mean cell sizes of irradiated tumors decreased ( < .005) after radiation treatment, which we associate with cell shrinkage and the formation of small cellular bodies during apoptosis and necrosis. A combination of IMPULSED-derived parameters (mean cell size and extracellular structural parameter ) separated 90% of irradiated tumors from the nonirradiated cases at post inoculation day 23, whereas a combination of tumor growth and conventional apparent diffusion coefficient did not differentiate irradiated tumors from nonirradiated tumors.
This proof-of-concept study demonstrates the IMPULSED method to be a new method for deriving quantitative microstructural parameters in a preclinical tumor model. The method provides unique information based on the diffusion time dependency of diffusion magnetic resonance imaging, which cannot be obtained by conventional diffusion weighted imaging methods, and the results have a close correlation with primary biologic markers of treatment efficacy, such as cell death and survival.
本研究旨在测试定量时间扩散光谱（qTDS）评估大鼠胶质瘤模型中与辐射诱导细胞死亡相关的细胞变化的能力。
在大鼠胶质瘤（9L）模型中研究了单次20 Gy X射线辐射的肿瘤反应。在接种后第21、23和25天纵向监测肿瘤反应，使用qTDS的一种特定实现方式，即首字母缩写为IMPULSED（使用有限光谱编辑扩散成像微观结构参数）的方法，以及传统扩散和高分辨率解剖成像。IMPULSED方法结合了在一系列扩散时间上采集的扩散加权信号，然后使用组织中水分子扩散的理论模型进行分析和解释，该模型生成体素级描绘细胞和亚细胞结构信息的参数图。对不同指标的结果进行统计学比较。
单次20 Gy X射线辐射显著延长了荷9L瘤大鼠的生存期。放疗后，受照射肿瘤的平均细胞大小减小（<0.005），我们将其与细胞凋亡和坏死过程中的细胞收缩以及小细胞体的形成相关联。在接种后第23天，IMPULSED衍生参数（平均细胞大小和细胞外结构参数）的组合将90%的受照射肿瘤与未受照射病例区分开来，而肿瘤生长和传统表观扩散系数的组合未能区分受照射肿瘤和未受照射肿瘤。
这项概念验证研究表明，IMPULSED方法是一种在临床前肿瘤模型中获取定量微观结构参数的新方法。该方法基于扩散磁共振成像的扩散时间依赖性提供独特信息，这是传统扩散加权成像方法无法获得的，且结果与治疗效果的主要生物学标志物如细胞死亡和存活密切相关。
