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深度学习定量分析小鼠脑肿瘤模型中的血管药代动力学参数。

Deep learning quantification of vascular pharmacokinetic parameters in mouse brain tumor models.

机构信息

Department of Biomedical Engineering, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.

Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.

出版信息

Front Biosci (Landmark Ed). 2022 Mar 16;27(3):99. doi: 10.31083/j.fbl2703099.

Abstract

BACKGROUND

Dynamic contrast-enhanced (DCE) MRI is widely used to assess vascular perfusion and permeability in cancer. In small animal applications, conventional modeling of pharmacokinetic (PK) parameters from DCE MRI images is complex and time consuming. This study is aimed at developing a deep learning approach to fully automate the generation of kinetic parameter maps, Ktrans (volume transfer coefficient) and Vp (blood plasma volume ratio), as a potential surrogate to conventional PK modeling in mouse brain tumor models based on DCE MRI.

METHODS

Using a 7T MRI, DCE MRI was conducted in U87 glioma xenografts growing orthotopically in nude mice. Vascular permeability Ktrans and Vp maps were generated using the classical Tofts model as well as the extended-Tofts model. These vascular permeability maps were then processed as target images to a twenty-four layer convolutional neural network (CNN). The CNN was trained on T1-weighted DCE images as source images and designed with parallel dual pathways to capture multiscale features. Furthermore, we performed a transfer study of this glioma trained CNN on a breast cancer brain metastasis (BCBM) mouse model to assess the potential of the network for alternative brain tumors.

RESULTS

Our data showed a good match for both Ktrans and Vp maps generated between the target PK parameter maps and the respective CNN maps for gliomas. Pixel-by-pixel analysis revealed intratumoral heterogeneous permeability, which was consistent between the CNN and PK models. The utility of the deep learning approach was further demonstrated in the transfer study of BCBM.

CONCLUSIONS

Because of its rapid and accurate estimation of vascular PK parameters directly from the DCE dynamic images without complex mathematical modeling, the deep learning approach can serve as an efficient tool to assess tumor vascular permeability to facilitate small animal brain tumor research.

摘要

背景

动态对比增强(DCE)MRI 广泛用于评估癌症中的血管灌注和通透性。在小动物应用中,从 DCE MRI 图像中对药代动力学(PK)参数进行传统建模既复杂又耗时。本研究旨在开发一种深度学习方法,以全自动生成动力学参数图,即 Ktrans(容积转移系数)和 Vp(血浆容积比),作为基于 DCE MRI 的小鼠脑肿瘤模型中替代传统 PK 建模的潜在方法。

方法

在裸鼠原位生长的 U87 神经胶质瘤异种移植中使用 7T MRI 进行 DCE MRI。使用经典的 Tofts 模型和扩展的 Tofts 模型生成血管通透性 Ktrans 和 Vp 图。然后,将这些血管通透性图作为目标图像输入到 24 层卷积神经网络(CNN)中。该 CNN 以 T1 加权 DCE 图像作为源图像进行训练,并设计有并行双通道,以捕获多尺度特征。此外,我们还对乳腺癌脑转移(BCBM)小鼠模型中的该胶质瘤训练的 CNN 进行了转移研究,以评估该网络对其他脑肿瘤的潜力。

结果

我们的数据显示,在胶质瘤中,目标 PK 参数图与各自的 CNN 图之间生成的 Ktrans 和 Vp 图之间具有良好的匹配。像素对像素分析显示肿瘤内通透性不均匀,这与 CNN 和 PK 模型一致。深度学习方法的实用性在 BCBM 的转移研究中进一步得到了证明。

结论

由于该方法可以从 DCE 动态图像中快速准确地估计血管 PK 参数,而无需复杂的数学建模,因此深度学习方法可以作为一种有效的工具来评估肿瘤血管通透性,从而促进小动物脑肿瘤研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31de/9048985/a39d38db76e1/nihms-1797007-f0001.jpg

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