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混合小鼠模型逼真度的提高可能不足以生成参考剂量学数据。

Improved realism of hybrid mouse models may not be sufficient to generate reference dosimetric data.

机构信息

UMR 1037 INSERM∕UPS, Centre de Recherche en Cancérologie de Toulouse, Toulouse F-31062, France.

出版信息

Med Phys. 2013 May;40(5):052501. doi: 10.1118/1.4800801.

Abstract

PURPOSE

Recent developments of hybrid realistic models, such as Moby (mouse) and Roby (rat) developed by Segars et al. ["Development of a 4-D digital mouse phantom for molecular imaging research," Mol. Imaging Biol. 6, 149-159 (2004)] have found several applications in preclinical experiments. Indeed, their improved realism and flexibility in terms of mass scaling represent an attractive option for absorbed dose calculations based on "representative" models. However, the range of radiations involved in small animal molecular imaging and radiotherapy is of the same order of magnitude as organs of interest dimensions. As a consequence, minor geometric variations between rodents may lead to major differences in absorbed dose calculations. This study aims at validating a voxel-based model for use in absorbed dose estimates with two Monte Carlo codes and at assessing the dosimetric impact of Moby-based models definition.

METHODS

The authors generated a 30 g-mouse phantom based on realistic hybrid model Moby (version 1). Dosimetric calculations (S-values, specific absorbed fraction) were performed with two Monte Carlo codes (MCNPX v2.7a and GATE v6.1) for (18)F, and a comparison with values published for Radiation Dose Assessment Resource realistic animal series was made. Several parameters such as material definition∕densities, fine suborgan segmentation for airways (trachea, lungs, remaining body), bones (ribs, spine, skull, remaining bones), heart (blood pool and myocardium), and stomach (wall and gastrointestinal content) were further studied, as well as nuclear data and spatial sampling.

RESULTS

Most organ masses matched the reference model (Moby v1) within ± 6%, except lungs, thyroid, and bones for which differences could reach 29%. Comparison of S-values (especially self-S-values) was consistent with mass differences observed between the two models. The reciprocity theorem for source∕target pairs was satisfied within few percents for specific absorbed fractions (g(-1)). However, significant discrepancies, reaching 160%, were observed for mutual liver∕stomach∕spleen S-values and could not be directly related to mass variations. Nonetheless, differences between S-values calculated with MCNPX and GATE for our model remained in the order of a few percents, i.e., within statistical uncertainties. Besides, modifications of organ densities increased S-values up to a factor 50 for the lungs∕thyroid pair when upper airway was properly segmented out of the body. Specific material composition and densities for several bone types led to a 10% decrease of S-values from the bone source to several target organs. Moreover, relative differences up to 100% were observed for S(stomach wall⇐spleen) when improving spatial-sampling by a factor 3.

CONCLUSIONS

This study demonstrated that comparison between two "similar" realistic digital mouse whole-body phantoms generated from the same software still led to very different S-values, even when total body and organ mass scaling were performed. Moreover, parameters such as organ segmentation, tissue material∕density, or spatial sampling should be defined and reported with great care to perform accurate small animal absorbed dose calculation based on "reference" models.

摘要

目的

Segars 等人开发的混合现实模型(如 Moby(鼠)和 Roby(鼠))等最近的发展,在临床前实验中找到了几种应用。事实上,它们在质量缩放方面的更高现实性和灵活性代表了基于“代表性”模型的吸收剂量计算的一个有吸引力的选择。然而,在小动物分子成像和放射治疗中涉及的辐射范围与感兴趣器官的尺寸相同。因此,啮齿动物之间的微小几何变化可能导致吸收剂量计算的主要差异。本研究旨在使用两种蒙特卡罗代码验证用于吸收剂量估计的体素模型,并评估基于 Moby 的模型定义的剂量学影响。

方法

作者基于真实混合模型 Moby(版本 1)生成了一个 30 克的鼠体模型。使用两种蒙特卡罗代码(MCNPX v2.7a 和 GATE v6.1)进行剂量计算(S 值、特定吸收分数),并与 Radiation Dose Assessment Resource 真实动物系列公布的值进行比较。进一步研究了材料定义/密度、气道(气管、肺、剩余体)、骨骼(肋骨、脊柱、颅骨、剩余骨骼)、心脏(血池和心肌)和胃(壁和胃肠道内容物)的精细子器官分割等参数,以及核数据和空间采样。

结果

大多数器官质量与参考模型(Moby v1)匹配,误差在±6%以内,除了肺、甲状腺和骨骼,其差异可达 29%。S 值的比较(尤其是自 S 值)与两个模型之间观察到的质量差异一致。源/目标对之间的互易定理在特定吸收分数(g(-1))的几个百分点内得到满足。然而,对于相互的肝/胃/脾 S 值,观察到高达 160%的显著差异,并且不能直接与质量变化相关。尽管如此,对于我们的模型,用 MCNPX 和 GATE 计算的 S 值之间的差异仍然在几个百分点以内,即统计不确定度内。此外,当正确地将上呼吸道与身体分开时,肺/甲状腺对的气道的器官密度增加可使 S 值增加 50 倍。几种骨类型的特定材料组成和密度导致从骨源到几个靶器官的 S 值降低 10%。此外,当通过因子 3 提高空间采样时,对于 S(stomach wall ⇐ spleen),观察到高达 100%的相对差异。

结论

本研究表明,即使进行了整体和器官质量缩放,比较两个基于相同软件生成的“相似”真实数字鼠全身模型仍然会导致非常不同的 S 值。此外,应非常小心地定义和报告器官分割、组织材料/密度或空间采样等参数,以基于“参考”模型进行准确的小动物吸收剂量计算。

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