Department of Physics, Oklahoma State University, Stillwater, 74078, OK, USA.
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, MA, USA.
Med Phys. 2017 May;44(5):1734-1746. doi: 10.1002/mp.12191. Epub 2017 Mar 30.
While positron emission tomography (PET) allows for the imaging of tissues activated by proton beams in terms of monitoring the therapy administered, most endogenous tissue elements are activated by relatively high-energy protons. Therefore, a relatively large distance off-set exists between the dose fall-off and activity fall-off. However, O(p,2p,2n) N has a relatively low energy threshold which peaks around 12 MeV and also a residual proton range that is approximately 1 to 2 mm. In this phantom study, we tested the feasibility of utilizing the N production peak as well as the differences in activity fall-off between early and late PET scans for proton range verification. One of the main purposes for this research was developing a proton range verification methodology that would not require Monte Carlo simulations.
Both monoenergetic and spread-out Bragg peak beams were delivered to two phantoms - a water-like gel and a tissue-like gel where the proton ranges came to be approximately 9.9 and 9.1 cm, respectively. After 1 min of postirradiation delay, the phantoms were scanned for a period of 30 min using an in-room PET. Two separate (Early and Late) PET images were reconstructed using two different postirradiation delays and acquisition times; Early PET: 1 min delay and 3 min acquisition, Late PET: 21 min delay and 10 min acquisition. The depth gradients of the PET signals were then normalized and plotted as functions of depth. The normalized gradient of the early PET images was subtracted from that of the late PET images, to observe the N activity distribution in relation to depth. Monte Carlo simulations were also conducted with the same set-up as the measurements stated previously.
The subtracted gradients show peaks at 9.4 and 8.6 cm in water-gel and tissue-gel respectively for both pristine and SOBP beams. These peaks are created in connection with the sudden change of N signals with depth and consistently occur 2 mm upstream to where N signals were most abundantly created (9.6 and 8.8 cm in water-gel and tissue-gel, respectively). Monte Carlo simulations provided similar results as the measurements.
The subtracted PET signal gradient peaks and the proton ranges for water-gel and tissue-gel show distance off-sets of 4 to 5 mm. This off-set may potentially be used for proton range verification using only the PET measured data without Monte Carlo simulations. More studies are necessary to overcome various limitations, such as perfusion-driven washout, for the feasibility of this technique in living patients.
正电子发射断层扫描（PET）可以通过监测所施予的治疗来实现对质子束激活组织的成像，但是，大多数内源性组织元素会被相对高能的质子激活。因此，剂量衰减与活性衰减之间存在相当大的距离偏移。然而， O(p,2p,2n) N 具有相对较低的能量阈值，峰值约为 12 MeV，并且残余质子射程约为 1 至 2 毫米。在这项体模研究中，我们测试了利用 N 产生峰值以及早期和晚期 PET 扫描之间的活性衰减差异来进行质子射程验证的可行性。这项研究的主要目的之一是开发一种不需要蒙特卡罗模拟的质子射程验证方法。
单能和展宽布拉格峰束分别输送到两个体模 - 水凝胶和组织样凝胶，质子射程分别约为 9.9 和 9.1 厘米。辐照后延迟 1 分钟后，使用室内 PET 对两个体模进行了 30 分钟的扫描。使用两个不同的辐照后延迟和采集时间重建了两个单独的（早期和晚期）PET 图像；早期 PET：延迟 1 分钟，采集 3 分钟；晚期 PET：延迟 21 分钟，采集 10 分钟。然后将 PET 信号的深度梯度归一化并绘制为深度函数。从晚期 PET 图像的归一化梯度中减去早期 PET 图像的归一化梯度，以观察 N 活性分布与深度的关系。还使用与之前所述测量相同的设置进行了蒙特卡罗模拟。
在水凝胶和组织凝胶中，原始和 SOBP 束的早期和晚期 PET 图像的归一化梯度均在 9.4 和 8.6 厘米处显示出峰值。这些峰值是与 N 信号随深度的突然变化有关的，并且始终出现在 N 信号最丰富的地方（水凝胶和组织凝胶中的 9.6 和 8.8 厘米处）上游 2 毫米处。蒙特卡罗模拟提供了与测量结果相似的结果。
水凝胶和组织凝胶的减去的 PET 信号梯度峰值和质子射程之间存在 4 至 5 毫米的距离偏移。这种偏移可能可用于仅使用 PET 测量数据而无需蒙特卡罗模拟进行质子射程验证。为了使该技术在活体患者中具有可行性，需要进行更多的研究以克服各种限制，例如灌注驱动的洗脱。
