Department of Physics, Ludwig Maximilians University, Garching, Germany.
European Synchrotron Radiation Facility, Grenoble, France.
Int J Radiat Oncol Biol Phys. 2018 Jul 15;101(4):965-984. doi: 10.1016/j.ijrobp.2018.03.063. Epub 2018 Apr 7.
Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection. In the present study, we explored the benefits and limitations of PCI-CT use for in vitro imaging of normal and cancerous brain neuromorphology after in vivo treatment with synchrotron-generated x-ray microbeam radiation therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals were visualization of the MRT effects on nervous tissue and a qualitative comparison of the results to the histologic and high-field magnetic resonance imaging findings.
MRT was administered in vivo to the brain of both healthy and cancer-bearing rats. At 45 days after treatment, the brain was dissected out and imaged ex vivo using propagation-based PCI-CT.
PCI-CT visualizes the brain anatomy and microvasculature in 3 dimensions and distinguishes cancerous tissue morphology, necrosis, and intratumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout the treatment target areas (eg, the formation of micrometer-thick radiation-induced tissue ablation). The observed neurostructures were confirmed by histologic and immunohistochemistry examination and related to the micro-magnetic resonance imaging data.
PCI-CT enabled a unique 3D neuroimaging approach for ex vivo studies on small animal models in that it concurrently delivers high-resolution insight of local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights the deep microvasculature. This method could assist experimental small animal neurology studies in the postmortem evaluation of neuropathology or treatment effects.
实验神经影像学提供了广泛的方法，可以对脑解剖形态进行可视化，甚至达到亚细胞细节的程度。然而，每种技术都有特定的检测机制，这导致在可实现的视场大小、空间分辨率和神经组织灵敏度之间存在折衷，从而导致部分样本覆盖、未解决的形态结构或神经元群体稀疏标记，并且通常还需要对样本进行解剖或其他有创操作。X 射线相衬成像计算机断层扫描（PCI-CT）是一种实验性成像方法，它可以同时提供亚微米级别的空间分辨率、高软组织灵敏度和离体完整啮齿动物大脑的全覆盖，而无需对样本进行解剖、染色或标记，也无需注射对比剂。在本研究中，我们探讨了 PCI-CT 在体内接受同步辐射微束放射治疗（MRT）治疗后，对正常和癌变大脑神经形态进行体外成像的优势和局限性，MRT 是一种空间分割的实验性高剂量放射外科。其目的是可视化 MRT 对神经组织的影响，并将结果与组织学和高场磁共振成像结果进行定性比较。
MRT 对健康和荷瘤大鼠的大脑进行体内治疗。治疗后 45 天，将大脑取出并进行离体基于传播的 PCI-CT 成像。
PCI-CT 可在 3 个维度上可视化大脑解剖结构和微血管，并区分癌变组织形态、坏死和肿瘤内铁和钙沉积物的积累。此外，PCI-CT 可检测整个治疗靶区的 MRT 效应（例如，形成微米级厚的辐射诱导组织消融）。观察到的神经结构通过组织学和免疫组织化学检查得到证实，并与微磁共振成像数据相关。
PCI-CT 实现了一种独特的小动物模型离体神经影像学 3D 方法，它同时提供了正常和癌变微环境中局部脑组织形态的高分辨率洞察，定位放射外科损伤，并突出深部微血管。该方法可在小动物神经学研究中，在死后评估神经病理学或治疗效果方面提供帮助。
