Kersemans Veerle, Beech John S, Gilchrist Stuart, Kinchesh Paul, Allen Philip D, Thompson James, Gomes Ana L, D'Costa Zenobia, Bird Luke, Tullis Iain D C, Newman Robert G, Corroyer-Dulmont Aurelien, Falzone Nadia, Azad Abul, Vallis Katherine A, Sansom Owen J, Muschel Ruth J, Vojnovic Borivoj, Hill Mark A, Fokas Emmanouil, Smart Sean C
Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.
Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
PLoS One. 2017 Apr 28;12(4):e0176693. doi: 10.1371/journal.pone.0176693. eCollection 2017.
Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse.
A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours.
The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk.
This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.
临床前CT引导放疗平台的应用越来越广泛,但CT图像的软组织对比度较差。本研究的目的是开发一种稳健且准确的方法,用于在小鼠体内对腹部靶区进行磁共振成像引导放疗(MR-IGRT)。
开发了一种多模态托架用于固定实验对象,并对其性能进行了评估。虽然CT仍用于剂量计算,但靶区识别基于磁共振成像。放疗计划程序的每个步骤最初都在体外使用BANG凝胶剂量计进行了验证。随后,使用尺寸匹配的准直光束对正常肾上腺进行了MR-IGRT。此外,还使用了SK-N-SH神经母细胞瘤异种移植模型和胰腺导管腺癌的转基因KPC模型,以证明我们的方法在将辐射准确传递至CT不可见的腹部肿瘤方面的适用性。
BANG凝胶体模的靶向效率误差为0.56±0.18毫米。MR-IGRT期间身体运动的体内稳定性测试以及相关的托架转移表明,残余身体运动在该MR-IGRT靶向误差范围内。通过γH2AX染色证实了使用尺寸匹配的准直光束对正常肾上腺进行的准确MR-IGRT。在神经母细胞瘤模型中,MR-IGRT后几乎立即观察到肿瘤体积缩小,进一步证明了X射线传递的准确性。最后,KPC模型中的MR-IGRT不仅有助于对不同治疗计划和放疗剂量分布进行精确轮廓绘制和比较,不仅针对腹内肿瘤,还针对危及器官。
据我们所知,这是第一项在腹部器官中展示临床前MR-IGRT的研究。所提出的MR-IGRT方法提供了一种先进的解决方案,能够在小鼠体内对颅外器官进行稳健、准确和高效的靶向,并且可以以足够高的通量运行,以进行分次治疗。