The role of necrosis, acute hypoxia and chronic hypoxia in (18)F-FMISO PET image contrast: a computational modelling study.
The role of necrosis, acute hypoxia and chronic hypoxia in (18)F-FMISO PET image contrast: a computational modelling study.
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DOI：
10.1088/1361-6560/61/24/8596
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发表时间：
2016-12-21
影响因子：
3.5
通讯作者：
Partridge M
中科院分区：
文献类型：
--
作者：
Warren DR;Partridge M
正电子发射断层扫描（PET）使用18F-氟咪唑（FMISO）是一种很有前途的技术，用于成像肿瘤缺氧，放射治疗剂量绘画的潜在目标。然而，FMISO摄取与氧分压（）之间的关系尚未完全量化。组织氧合在远小于临床PET分辨率的距离上变化（<100 μm与<104 mm），并且在比典型FMISO PET研究短的时间尺度上观察到肿瘤灌注的周期性变化（<20分钟与几小时）。此外，在含有一定程度坏死的体素中，示踪剂摄取可能减少。这项工作开发了一个计算模型FMISO吸收毫米级肿瘤区域。耦合偏微分方程支配氧气和FMISO分布的演变，并且动态血管源图表示灌注的时间变化。局部FMISO结合能力由坏死部分调节。输出包括时空图和示踪剂的积累，使计算的组织-血液比（TBRs）和时间-活性曲线（TAC）作为平均组织氧合的函数。使用实验数据对模型进行表征，发现局部1.4 mmHg（95% CI：0.3-2.6 mmHg）下的半最大FMISO结合和1.2 mmHg（0.1-4.9 mmHg）下的半最大坏死。模拟预测FMISO活性（注射后4小时）和平均组织之间的非线性非单调关系：示踪剂摄取从无血管组织中可忽略的水平急剧上升，在1.55 mmHg达到峰值，并在氧合良好的条件下向血液活性下降。灌注的较大时间变化增加了峰值TBRs（范围2.20-5.27），这是由于预测的坏死分数较小，而不是急性缺氧下FMISO蓄积的根本差异。相同的晚期FMISO摄取可以发生在具有不同坏死分数的区域，但模拟的TAC表明，额外的早期信息可能允许区分缺氧和坏死信号。我们的结论是，一个强大的方法FMISO解释（和剂量绘画处方）很可能是基于动态PET分析。
Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy dose-painting. However, the relationship between FMISO uptake and oxygen partial pressure () is yet to be quantified fully. Tissue oxygenation varies over distances much smaller than clinical PET resolution (<100 μm versus ∼4 mm), and cyclic variations in tumour perfusion have been observed on timescales shorter than typical FMISO PET studies (∼20 min versus a few hours). Furthermore, tracer uptake may be decreased in voxels containing some degree of necrosis. This work develops a computational model of FMISO uptake in millimetre-scale tumour regions. Coupled partial differential equations govern the evolution of oxygen and FMISO distributions, and a dynamic vascular source map represents temporal variations in perfusion. Local FMISO binding capacity is modulated by the necrotic fraction. Outputs include spatiotemporal maps of and tracer accumulation, enabling calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a function of mean tissue oxygenation. The model is characterised using experimental data, finding half-maximal FMISO binding at local of 1.4 mmHg (95% CI: 0.3–2.6 mmHg) and half-maximal necrosis at 1.2 mmHg (0.1–4.9 mmHg). Simulations predict a non-linear non-monotonic relationship between FMISO activity (4 hr post-injection) and mean tissue : tracer uptake rises sharply from negligible levels in avascular tissue, peaking at ∼5 mmHg and declining towards blood activity in well-oxygenated conditions. Greater temporal variation in perfusion increases peak TBRs (range 2.20–5.27) as a result of smaller predicted necrotic fraction, rather than fundamental differences in FMISO accumulation under acute hypoxia. Identical late FMISO uptake can occur in regions with differing and necrotic fraction, but simulated TACs indicate that additional early-phase information may allow discrimination of hypoxic and necrotic signals. We conclude that a robust approach to FMISO interpretation (and dose-painting prescription) is likely to be based on dynamic PET analysis.
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