The Low Hepatic Toxicity per Gray of 90Y Glass Microspheres Is Linked to Their Transport in the Arterial Tree Favoring a Nonuniform Trapping as Observed in Posttherapy PET Imaging
The Low Hepatic Toxicity per Gray of 90Y Glass Microspheres Is Linked to Their Transport in the Arterial Tree Favoring a Nonuniform Trapping as Observed in Posttherapy PET Imaging
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DOI：
10.2967/jnumed.113.126839
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发表时间：
2014-01-01
影响因子：
9.3
通讯作者：
Jamar, Francois
中科院分区：
文献类型：
--
作者：
Walrand, Stephan;Hesse, Michel;Jamar, Francois
Y-90树脂和玻璃微球肝放射栓塞分别给予70 Gy和120 Gy的大叶剂量，显示出与40 Gy分次外束放疗相似的肝毒性。我们研究了较低数量的玻璃微球如何引起足够不均匀的剂量分布来解释这一悖论。方法：在Gulec等人建立的真实肝脏模型中使用Russell剂量沉积核进行微尺度剂量测定。六边形棱镜的晶格表示肝小叶。采用固定长度和可变长度两种肝动脉树模型进行微球运输。假设两个子血管之间的微球相对扩散概率相等或不对称。进行了几次120 gy的肝脏模拟：周期性模拟，其中1或6个玻璃微球分别被捕获在所有门静脉束中，仅在6个门静脉束中的1个中，以及随机模拟，其中玻璃微球捕获在所有门静脉束中假设相同的概率，或者根据通往门静脉束的动脉连接的先后顺序假设可变概率，这两种模型都适用于两种动脉树模型。结果：在2个均匀模拟中，所有肝脏结构均接受了至少100 Gy的辐射。Y-90核的快速减少作为距离r平方的倒数，被含有微球的贡献小叶的数量随着r(2)而增加所抵消。等扩散概率的随机模拟结果表明，受辐照较少的组织以103 Gy为中心的小叶剂量分布（最大半宽处全宽20 Gy）。分布明显不对称，相对扩散概率为60% ~ 40%，最大值从103 Gy下降到50 Gy，约17%的小叶受到低于40 Gy的剂量。结论：微球在动脉树运输过程中产生的大量不均匀捕获以及注射玻璃微球的数量较少开始解释其较低的肝毒性。此外，不均匀的捕获支持这样一个事实，即在患者中观察到的Y-90 PET成像的颗粒方面可以代表一些现实，而不仅仅是统计噪声。
Y-90 resin and glass microsphere liver radioembolizations delivering lobar doses of 70 and 120 Gy, respectively, display hepatic toxicity similar to 40-Gy fractionated external-beam radiotherapy. We investigated how the lower number of glass microspheres could induce a sufficiently nonuniform dose distribution explaining this paradox. Methods: Microscale dosimetry was assessed in the realistic liver model developed by Gulec et al. but using the Russell's dose deposition kernel. A lattice of hexagonal prisms represented the hepatic lobules. Two hepatic arterial tree models-that is, a fixed-length and a variable-branches length-were used for the microsphere transport. Equal or asymmetric microsphere relative-spreading probability between 2 daughter vessels was assumed. Several 120-Gy liver simulations were performed: periodic simulations, where 1 or 6 glass microspheres were trapped in all and in only 1 of 6 portal tracts, respectively, and random simulations, where glass microsphere trapping assumed an equal probability for all the portal tracts or a variable probability depending on the successions of artery connections leading to the portal tract, both for the 2 arterial tree models. Results: For the 2 uniform simulations, all hepatic structures received at least 100 Gy. The fast decrease of the Y-90 kernel as the inverse of the square of the distance r is counterbalanced by the number of contributing lobules containing microspheres that increases as r(2). The random simulation with equal-spreading probability gave for the less irradiated tissue a lobule dose distribution centered around 103 Gy (full width at half maximum, 20 Gy). The distribution became significantly asymmetric with the 60%-40% relative-spreading probability, with a shift of the maximum from 103 down to 50 Gy, and about 17% of the lobules got a dose lower than 40 Gy to their different structures. Conclusion: The large nonuniform trapping produced by the microsphere transport in the arterial tree jointly with the low number of injected glass microspheres begins to explain their lower hepatic toxicity per Gray. In addition, the nonuniform trapping supports the fact that the granular aspect of Y-90 PET imaging observed in patients could represent some reality and not only statistical noise.