A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance.
A precision 3D conformal treatment technique in rats: Application to whole-brain radiotherapy with hippocampal avoidance.
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DOI：
10.1002/mp.12533
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发表时间：
2017-11
期刊：
影响因子：
3.8
通讯作者：
Oldham M
中科院分区：
文献类型：
--
作者：
Yoon SW;Cramer CK;Miles DA;Reinsvold MH;Joo KM;Kirsch DG;Oldham M
利用精确的3D打印固定和微块开发和验证Wistar大鼠的3D适形海马保留全脑放射治疗（HA-WBRT）。这项技术为未来的临床前研究铺平了道路，研究减少神经毒性的大脑治疗方法。开发了一种新的临床前治疗计划和输送过程，以实现Xrad 225 cx小动物辐照器的精确3D适形治疗和海马回避能力。评估了一系列共形回避计划，这些计划由等角度间隔的共面轴向射束组成，计划包含2、4、7和8个射野。通过Monte Carlo剂量计算（SmART-Plan Xrad 225 cx计划系统）研究这些计划的海马保留和覆盖。通过一种新的方法实施治疗，其中从MRI大鼠图谱中计算机生成海马块形状，该图谱与处于治疗位置的大鼠的机载锥束CT配准。这些块是用掺杂钨的细丝3D打印的，横向分辨率为80μm。利用3D打印的支撑系统实现了精确的固定，该支撑系统使大鼠头部能够以仰卧位和咬合块的角度定位，以改善中央间脑的覆盖范围。在以0.2 mm各向同性分辨率光学扫描的啮齿动物形态Presage® 3D剂量计上验证治疗输送。海马回避的生物学验证进行免疫组织化学染色。所有模拟计划均保留海马，同时向大脑输送高剂量（在平均海马剂量为7 Gy时，大脑平均剂量为22.5-26.2Gy）。通过增加超过4个视野的光束，没有观察到海马保留的显著改善。使用Presage®剂量计验证4-射野计划的海马区的剂量测定保留（平均剂量= 9.6 Gy，D100% = 7.1 Gy）。模拟和剂量计在2 mm的一致性距离和± 3%的剂量差下匹配，γ通过率为91.7%（γ<1的通过标准）。在1 mm和± 5%处的一致性较小，伽马射线通过率为69.0%。进一步验证免疫组化的4场计划，并显示出显着减少的DNA双链断裂的备用区域相比，全脑照射组（p = 0.021）。然而，全脑的覆盖率较低，在7 Gy平均海马剂量下，模拟中为48.5-57.8%的接受30 Gy的体积，剂量学测量中为46.7-52.5%。这可归因于大鼠海马的形状和治疗平台不能采用非共面光束。开发、实施和验证了一种使用3D打印技术进行适形微放射治疗的新方法。开发了一个工作流程，以从注册的高分辨率大鼠MRI图谱结构中生成准确的3D打印块。虽然海马是用这种技术幸免，整个大脑的目标覆盖率是次优的，这表明，非共面射束和调强放射治疗能力可能是必需的，以满足严格的剂量标准与目前的人类RTOG试验。
To develop and validate 3D conformal hippocampal sparing whole-brain radiation therapy (HA-WBRT) for Wistar rats utilizing precision 3D printed immobilization and micro-blocks. This technique paves the way for future pre-clinical studies investigating brain treatments that reduce neurotoxicity. A novel pre-clinical treatment planning and delivery process was developed to enable precision 3D conformal treatment and hippocampal avoidance capability for the Xrad 225cx small animal irradiator. A range of conformal avoidance plans were evaluated consisting of equi-angularly spaced co-planar axial beams, with plans containing 2, 4, 7, and 8 fields. The hippocampal sparing and coverage of these plans were investigated through Monte Carlo dose calculation (SmART-Plan Xrad 225cx planning system). Treatment delivery was implemented through a novel process where hippocampal block shapes were computer-generated from an MRI rat atlas which was registered to on-board cone-beam-CT of the rat in treatment position. The blocks were 3D-printed with a tungsten-doped filament at lateral resolution of 80μm. Precision immobilization was achieved utilizing a 3D-printed support system which enabled angled positioning of the rat head in supine position and bite-block to improve coverage of the central diencephalon. Treatment delivery was verified on rodent-morphic Presage® 3D dosimeters optically scanned at 0.2mm isotropic resolution. Biological verification of hippocampal avoidance was performed with immunohistologic staining. All simulated plans spared the hippocampus while delivering high dose to the brain (22.5-26.2Gy mean dose to brain at mean hippocampal dose of 7Gy). No significant improvement in hippocampal sparing was observed by adding beams beyond 4 fields. Dosimetric sparing of hippocampal region of the 4-field plan was verified with the Presage® dosimeter (mean dose = 9.6Gy, D100% = 7.1Gy). Simulation and dosimeter match at distance-to-agreement of 2mm and dose difference of ±3%, at 91.7% gamma passing rate (passing criteria of γ<1). Agreement is less at 1mm and ±5%, at 69.0% gamma passing rate. The 4-field plan was further validated with immunohistochemistry, and showed a significant reduction in DNA double strand breaks within the spared region compared to whole-brain irradiated groups (p = 0.021). However, coverage of the whole brain was low at 48.5-57.8% of the volume receiving 30Gy at 7Gy mean hippocampal dose in simulation and 46.7-52.5% in dosimetric measurements. This can be attributed to the shape of the rat hippocampus and the inability of treatment platform to employ non-coplanar beams. A novel approach for conformal micro-radiation-therapy using 3D-printing technology was developed, implemented, and validated. A workflow was developed to generate accurate 3D-printed blocks from registered high-resolution rat MRI atlas structures. Though hippocampus was spared with this technique, whole brain target coverage was sub-optimal, indicating that non-coplanar beams and IMRT capability may be required in order to meet stringent dose criteria associated with current human RTOG trials.
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影响因子：
3.8
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