S 指数作为一种扩散 MRI 生物标志物与磁共振波谱联合评估放射性脑损伤的纵向研究。

Longitudinal Study of Irradiation-Induced Brain Microstructural Alterations With S-Index, a Diffusion MRI Biomarker, and MR Spectroscopy.

机构信息

NeuroSpin, Frédéric Joliot Institute, Division of Fondamental Research, French Alternative Energy and Atomic Energy Commission, Université Paris-Saclay, Gif-sur-Yvette, France; Laboratoire de Radiopathologie, UMR967, Institute of Cellular and Molecular Radiobiology, François Jacob Institute, Division of Fondamental Research, French Alternative Energy and Atomic Energy Commission, French National Institute of Health and Medical Research, Universités Paris-Saclay and Paris-Diderot, Fontenay-aux-Roses, France.

Laboratoire de Radiopathologie, UMR967, Institute of Cellular and Molecular Radiobiology, François Jacob Institute, Division of Fondamental Research, French Alternative Energy and Atomic Energy Commission, French National Institute of Health and Medical Research, Universités Paris-Saclay and Paris-Diderot, Fontenay-aux-Roses, France.

出版信息

Int J Radiat Oncol Biol Phys. 2018 Nov 15;102(4):1244-1254. doi: 10.1016/j.ijrobp.2018.01.070. Epub 2018 Feb 2.

DOI:10.1016/j.ijrobp.2018.01.070

PMID:29680253

Abstract

PURPOSE

Radiation therapy is widely used for the treatment of brain tumors, but it may lead to severe cognitive impairments. Previous studies have shown that ionizing irradiation induces demyelination, blood-brain barrier alterations, and impaired neurogenesis in animal models. Hence, noninvasive and sensitive biomarkers of irradiation injury are needed to investigate these effects in patients and improve radiation therapy protocols.

METHODS AND MATERIALS

The heads of 3-month-old male C57BL/6RJ mice (15 control mice and 15 irradiated mice) were exposed to radiation doses of 3 fractions of 5 Gy from a Co source with a medical irradiator. A longitudinal study was performed to investigate cranial irradiation-induced (3 fractions of 5 Gy) microstructural tissue alterations using water diffusion magnetic resonance imaging and magnetic resonance spectroscopy in different areas of the mouse brain (cortex, thalamus, striatum, olfactory bulbs [OBs], hippocampus, and subventricular zone [SVZ]). In addition to the quantification of standard non-Gaussian diffusion parameters, apparent diffusion coefficient (ADC) and kurtosis (K), we evaluated a new composite diffusion metric, designated the S-index (ie, "signature index").

RESULTS

We observed a significant decrease in the S-index in the SVZ from 1 month to 8 months after brain irradiation (P < .05). An interesting finding was that, along with a decrease in taurine levels (up to -15% at 2 months, P < .01), a delayed S-index drop was observed in the OBs from 4 months after irradiation and maintained until the end of our experiment (P < .0001). These observations suggest that S-index variations revealed the irradiation-induced decline of neurogenesis that was further confirmed by a decrease in neural stem cells in the SVZ and in newborn neurons in the OBs of irradiated animals.

CONCLUSIONS

This study demonstrates that diffusion magnetic resonance imaging, especially through the S-index approach, is a relevant imaging modality to monitor brain irradiation injury and probe microstructural changes underlying irradiation-induced cognitive deficits.

摘要

目的

放射疗法广泛用于治疗脑肿瘤，但可能导致严重的认知障碍。先前的研究表明，电离辐射会在动物模型中引起脱髓鞘、血脑屏障改变和神经发生受损。因此，需要非侵入性和敏感的辐射损伤生物标志物来研究这些在患者中的影响，并改进放射治疗方案。

方法和材料

将 3 个月大的雄性 C57BL/6RJ 小鼠（15 只对照小鼠和 15 只照射小鼠）的头部暴露于来自 Co 源的 3 次 5 Gy 分次照射剂量的医疗辐照器下。进行了一项纵向研究，以使用水扩散磁共振成像和磁共振波谱研究不同脑区（皮质、丘脑、纹状体、嗅球[OB]、海马体和侧脑室下区[SVZ]）中颅辐射诱导（3 次 5 Gy）的微观结构组织改变。除了量化标准的非高斯扩散参数（表观扩散系数 ADC 和峰度 K）外，我们还评估了一种新的复合扩散指标，称为 S 指数（即“特征指数”）。

结果

我们观察到，从脑照射后 1 个月到 8 个月，SVZ 的 S 指数显著下降（P<.05）。一个有趣的发现是，随着牛磺酸水平的下降（2 个月时下降至-15%，P<.01），照射后 4 个月 OB 中的 S 指数下降延迟，并且一直持续到我们的实验结束（P<.0001）。这些观察结果表明，S 指数的变化揭示了照射诱导的神经发生下降，这进一步通过 SVZ 中的神经干细胞和照射动物 OB 中的新生神经元减少得到证实。