Rabinov James D, Brisman Jonathan L, Cole Andrew J, Lee Patricia Lani, Bussiere Marc R, Chapman Paul H, Loeffler Jay S, Cosgrove G Rees, Chaves Tina, Gonzalez R Gilberto
Division of Neuroradiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Stereotact Funct Neurosurg. 2004;82(4):156-64. doi: 10.1159/000081639. Epub 2004 Oct 19.
To define radiographic dose-response relationships for proton radiosurgery using a rat brain model.
A group of 23 rats was treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 5, 12, 20, 30, 60, 90 and 130 cobalt gray equivalents (CGE) were delivered to groups of 3 animals using single fraction technique. One extra animal was included at the 130- and 30-CGE doses. Animals were imaged using a standard 1.5-tesla GE Signa MRI. A 3-inch surface coil was employed to obtain T1-weighted sagittal images (TR 600 and TE 30) and dual echo T2-weighted coronal images (TR 3,000 and TE 30/90). Animals were imaged at 1.5, 3, 4.5, 6 and 9 months. Volumetric analysis with custom software was done to evaluate areas of increased signal on T2-weighted images, and signal change versus time curves were generated. Gadolinium-enhanced T1-weighted imaging was also done at the 9-month time point to further evaluate tissue injury. The development of hydrocephalus was also examined.
Peak tissue injury was greater and occurred earlier with higher versus lower doses of radiation. Statistically significant differences were seen between the 130- and 90-CGE animals and between the 90- and 60-CGE animals (p < 0.0016) using ANOVA. Signal changes can be seen in at least 1 of the animals at 20 CGE. The largest volume of tissue enhancement at 9 months was seen in animals at 60 CGE, which may represent an intermediate zone of tissue injury and gliosis compared with greater tissue loss at higher doses and less injury at lower doses. Hydrocephalus developed first in the untreated hemisphere in 130- and 90-CGE animals as a result of mass effect while it occurred at a later time in the treated hemisphere in lower-dose animals.
Following single-dose proton radiosurgery of rat hippocampus, serial MRIs show T2 signal changes in animals ranging from 130 down to 20 CGE as well as the development of hydrocephalus. Dose-effect relationships using proton radiosurgery in rats will be a helpful step in guiding further studies on radiation injury to brain tissue.
使用大鼠脑模型确定质子放射外科的放射剂量-反应关系。
一组23只大鼠接受了涉及右侧海马体的布拉格峰质子束照射。采用单次分割技术，将5、12、20、30、60、90和130钴灰当量（CGE）的单剂量分别给予每组3只动物。在130-CGE和30-CGE剂量组额外增加了1只动物。使用标准的1.5特斯拉GE Signa MRI对动物进行成像。采用3英寸表面线圈获取T1加权矢状位图像（TR 600和TE 30）以及双回波T2加权冠状位图像（TR 3000和TE 30/90）。在1.5、3、4.5、6和9个月时对动物进行成像。使用定制软件进行体积分析，以评估T2加权图像上信号增强的区域，并生成信号变化与时间的曲线。在9个月时间点还进行了钆增强T1加权成像，以进一步评估组织损伤。同时也检查了脑积水的发生情况。
与低剂量辐射相比，高剂量辐射导致的峰值组织损伤更大且出现更早。使用方差分析（ANOVA）发现，130-CGE组和90-CGE组动物之间以及90-CGE组和60-CGE组动物之间存在统计学显著差异（p < 0.0016）。在20 CGE时，至少有1只动物出现信号变化。9个月时，60 CGE组动物的组织增强体积最大，与高剂量时更大的组织损失和低剂量时较少的损伤相比，这可能代表了组织损伤和胶质增生的中间区域。在130-CGE和90-CGE组动物中，由于占位效应，脑积水首先在未治疗的半球出现，而在低剂量组动物中，脑积水在治疗半球出现的时间较晚。
对大鼠海马体进行单次剂量质子放射外科手术后，系列MRI显示，剂量范围从130 CGE降至20 CGE的动物出现T2信号变化以及脑积水。大鼠质子放射外科的剂量-效应关系将有助于指导对脑组织辐射损伤的进一步研究。
