Program in Molecular Medicine, SickKids Research Institute, Toronto, ON, Canada.
Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
Pediatr Radiol. 2024 Oct;54(11):1906-1918. doi: 10.1007/s00247-024-06048-7. Epub 2024 Sep 17.
Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of in vivo radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies.
Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography.
Prospective single-site study of 27 children. Blood collected pre and post neuroangiography, from which PBMC were isolated and assayed for biomarkers of mitochondrial stress (mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial DNA (mtDNA)) and DNA damage (γH2AX). Dose response of biomarkers vs. radiation dose was analyzed using linear regressions. The cohort was divided into higher (HD) and lower dose (LD) groups and analyzed using linear mixed models and compared using Welch's t-tests.
No biomarker exhibited a dose-dependent response following radiation (γH2AX: R = 0.0012, P = 0.86; MMP: R = 0.016, P = 0.53; mtDNA: R = 0.10, P = 0.11; ROS: R = 0.0023, P = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, P = 0.92; HD: -7.5 ± 6.3 AU, P = 0.24; ROS: LD: 1.3 ± 2.8, P = 0.64; HD: -3.6 ± 3.0 AU, P = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, P = 0.0014) and mtDNA (-1.1 ± 0.4 AU, P = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, P = 0.090; mtDNA: 0.2 ± 0.4, P = 0.65).
Biomarkers of mitochondrial stress in PBMC were identified during pediatric neuroangiography and warrant further investigation for radiation biodosimetry. However, isolating radiation-specific effects from those of procedural stress and general anesthesia requires further investigation.
神经血管造影术是一种重要的诊断和治疗影像学方法，但其中的辐射可能会对儿童造成影响。如果能发现与辐射相关的细胞损伤生物标志物，这将有助于我们进一步理解辐射的作用机制，并为开发辐射防护策略提供帮助。
检测接受神经血管造影术的儿童外周血单个核细胞（peripheral blood mononuclear cells，PBMC）中是否存在细胞损伤的生物标志物。
前瞻性单站点研究纳入了 27 名儿童。在神经血管造影术前和术后采集患儿的血液，分离 PBMC 并检测其线粒体应激（线粒体膜电位（mitochondrial membrane potential，MMP）、活性氧（reactive oxygen species，ROS）和线粒体 DNA（mitochondrial DNA，mtDNA））和 DNA 损伤（γH2AX）的生物标志物。采用线性回归分析生物标志物与辐射剂量之间的剂量反应关系。根据辐射剂量的高低，将研究对象分为高剂量（high-dose，HD）和低剂量（low-dose，LD）组，采用线性混合模型进行分析，并采用 Welch's t 检验进行组间比较。
没有生物标志物表现出与辐射剂量相关的剂量反应（γH2AX：R=0.0012，P=0.86；MMP：R=0.016，P=0.53；mtDNA：R=0.10，P=0.11；ROS：R=0.0023，P=0.81）。组间比较显示，γH2AX 和 ROS 在接受辐射后没有显著差异（γH2AX：LD：0.6±6.0，P=0.92；HD：-7.5±6.3 AU，P=0.24；ROS：LD：1.3±2.8，P=0.64；HD：-3.6±3.0 AU，P=0.24）。我们观察到线粒体标志物 MMP（-53.7±14.7 AU，P=0.0014）和 mtDNA（-1.1±0.4 AU，P=0.0092）在高剂量组有显著变化，但在低剂量组没有（MMP：26.1±14.7 AU，P=0.090；mtDNA：0.2±0.4，P=0.65）。
在儿科神经血管造影术中检测到 PBMC 中的线粒体应激生物标志物，这为进一步研究辐射生物剂量学提供了依据。但是，要想从程序性应激和全身麻醉的影响中分离出辐射特异性影响，还需要进一步研究。
