Applying a patient-specific bio-mathematical model of glioma growth to develop virtual [18F]-FMISO-PET images
Applying a patient-specific bio-mathematical model of glioma growth to develop virtual [18F]-FMISO-PET images
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DOI：
10.1093/imammb/dqr002
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发表时间：
2012-03-01
影响因子：
1.1
通讯作者：
Swanson, Kristin R.
中科院分区：
文献类型：
--
作者：
Gu, Stanley;Chakraborty, Gargi;Swanson, Kristin R.
多形性胶质母细胞瘤（GBM）是一类原发性脑肿瘤，其特征在于它们能够快速增殖和弥漫性浸润周围脑组织。GBM的侵袭性生长导致低氧（缺氧）区域的发展，这可以通过[18 F]-氟咪唑（FMISO）正电子发射断层扫描（PET）成像进行临床评估。在我们以前的数学建模工作取得成功的基础上，我们扩大了我们的模型，包括肿瘤微环境，特别是缺氧，坏死和血管生成。FMISO-PET示踪剂的药代动力学模型应用于整个大脑的每个空间位置，并且将用于图像采集和重建方法的分析模拟器应用于所得示踪剂活性图。我们的解剖模型与FMISO示踪剂动力学和PET图像重建模型的组合能够产生患者特异性虚拟PET图像，该图像再现临床PET扫描的图像特征，并且在肿瘤内的缺氧分布中没有显示统计学差异。这项工作建立了解剖（磁共振成像[MRI]）和分子（PET）成像之间的联系，在患者特定的基础上的原则证明，以及解决其他站不住脚的问题，在分子成像，如确定从细胞密度示踪剂活性的影响。虽然需要进一步研究来确定该技术的预测值，但这种独特的工具提供了对MRI上观察到的解剖学变化与体内GBM PET上观察到的生化活性之间的生物学联系的更好的动态理解。
Glioblastoma multiforme (GBM) is a class of primary brain tumours characterized by their ability to rapidly proliferate and diffusely infiltrate surrounding brain tissue. The aggressive growth of GBM leads to the development of regions of low oxygenation (hypoxia), which can be clinically assessed through [18F]-fluoromisonidazole (FMISO) positron emission tomography (PET) imaging. Building upon the success of our previous mathematical modelling efforts, we have expanded our model to include the tumour microenvironment, specifically incorporating hypoxia, necrosis and angiogenesis. A pharmacokinetic model for the FMISO-PET tracer is applied at each spatial location throughout the brain and an analytical simulator for the image acquisition and reconstruction methods is applied to the resultant tracer activity map. The combination of our anatomical model with one for FMISO tracer dynamics and PET image reconstruction is able to produce a patient-specific virtual PET image that reproduces the image characteristics of the clinical PET scan as well as shows no statistical difference in the distribution of hypoxia within the tumour. This work establishes proof of principle for a link between anatomical (magnetic resonance image [MRI]) and molecular (PET) imaging on a patient-specific basis as well as address otherwise untenable questions in molecular imaging, such as determining the effect on tracer activity from cellular density. Although further investigation is necessary to establish the predicitve value of this technique, this unique tool provides a better dynamic understanding of the biological connection between anatomical changes seen on MRI and biochemical activity seen on PET of GBM in vivo.