Université de Toulouse, UPS, Centre de Recherche Cerveau et Cognition, Toulouse, France.
PLoS One. 2010 Feb 3;5(2):e9028. doi: 10.1371/journal.pone.0009028.
Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 microm wide, spaced 200 microm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm(3) in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of synchrotron-generated X-rays enables delivery of high doses for destruction of small focal regions in human brains, with sharper dose fall-offs than those described in any other conventional radiation therapy.
微束放射治疗（MRT）是一种专门用于脑肿瘤治疗的放射外科的临床前形式。它基于空间束分割，使用微米宽的同步加速器产生的 X 射线束。由于正常脑脉管系统对 MRT 的放射抗性，持续的血液供应可以维持，这部分解释了正常组织对非常高的辐射剂量（数百 Gy）的惊人耐受性。基于微平面束对正常组织的这种良好描述的保护作用，我们开发了一种新的照射几何形状，该几何形状允许在给定的脑靶区中递送高均匀剂量沉积，而周围的正常组织仅受到可耐受的平行微束照射。正常大鼠大脑暴露于 4 个局部交错的 10 个微平面束阵列（52 微米宽，中心间距 200 微米，能量范围为 50 至 350 keV），从 4 个不同的端口靶向，每个端口的峰值入口剂量为 200Gy，以将均匀剂量递送至尾状核的 7mm3 目标体积。大鼠的磁共振成像（MRI）随访显示，血管通透性在照射后 1 周开始出现高度局部增加。造影剂扩散局限于靶区，并且在照射后 1 个月仍可观察到，同时伴有组织病理学改变，包括受损的血管。在靶区周围的正常脑组织中未检测到血管通透性变化。交错照射引起的癫痫大鼠自发性发作减少，说明了这种新照射几何形状的潜在临床前应用。最后，在一个人体大小的头部模型上进行的蒙特卡罗模拟表明，同步加速器光子可用于人类放射外科应用。我们的数据表明，交错微束照射可在脑靶区中实现高均匀剂量沉积，并导致局限的组织坏死，同时保护周围组织。同步加速器产生的 X 射线的使用可实现用于破坏人脑中小焦点区域的高剂量，与任何其他常规放射治疗相比，剂量下降更陡峭。
