Kaley A. Hogarth, Nicholas A. Shkumat, Simal Goman, Afsaneh Amirabadi, Suzanne Bickford, Prakash Muthusami, Bairbre L. Connolly, Jason T. Maynes
{"title":"儿科导管引导神经血管造影过程中线粒体应激和DNA损伤的生物标志物--一项前瞻性单中心研究","authors":"Kaley A. Hogarth, Nicholas A. Shkumat, Simal Goman, Afsaneh Amirabadi, Suzanne Bickford, Prakash Muthusami, Bairbre L. Connolly, Jason T. Maynes","doi":"10.1007/s00247-024-06048-7","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of <i>in vivo</i> radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography.</p><h3 data-test=\"abstract-sub-heading\">Materials and methods</h3><p>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 <i>t</i>-tests.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>No biomarker exhibited a dose-dependent response following radiation (γH2AX: <i>R</i><sup>2</sup> = 0.0012, <i>P</i> = 0.86; MMP: <i>R</i><sup>2</sup> = 0.016, <i>P</i> = 0.53; mtDNA: <i>R</i><sup>2</sup> = 0.10, <i>P</i> = 0.11; ROS: <i>R</i><sup>2</sup> = 0.0023, <i>P</i> = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, <i>P</i> = 0.92; HD: -7.5 ± 6.3 AU, <i>P</i> = 0.24; ROS: LD: 1.3 ± 2.8, <i>P</i> = 0.64; HD: -3.6 ± 3.0 AU, <i>P</i> = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, <i>P</i> = 0.0014) and mtDNA (-1.1 ± 0.4 AU, <i>P</i> = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, <i>P</i> = 0.090; mtDNA: 0.2 ± 0.4, <i>P</i> = 0.65).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>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.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":19755,"journal":{"name":"Pediatric Radiology","volume":"51 1","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography – a prospective single-center study\",\"authors\":\"Kaley A. Hogarth, Nicholas A. Shkumat, Simal Goman, Afsaneh Amirabadi, Suzanne Bickford, Prakash Muthusami, Bairbre L. Connolly, Jason T. Maynes\",\"doi\":\"10.1007/s00247-024-06048-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of <i>in vivo</i> radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies.</p><h3 data-test=\\\"abstract-sub-heading\\\">Objective</h3><p>Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography.</p><h3 data-test=\\\"abstract-sub-heading\\\">Materials and methods</h3><p>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 <i>t</i>-tests.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>No biomarker exhibited a dose-dependent response following radiation (γH2AX: <i>R</i><sup>2</sup> = 0.0012, <i>P</i> = 0.86; MMP: <i>R</i><sup>2</sup> = 0.016, <i>P</i> = 0.53; mtDNA: <i>R</i><sup>2</sup> = 0.10, <i>P</i> = 0.11; ROS: <i>R</i><sup>2</sup> = 0.0023, <i>P</i> = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, <i>P</i> = 0.92; HD: -7.5 ± 6.3 AU, <i>P</i> = 0.24; ROS: LD: 1.3 ± 2.8, <i>P</i> = 0.64; HD: -3.6 ± 3.0 AU, <i>P</i> = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, <i>P</i> = 0.0014) and mtDNA (-1.1 ± 0.4 AU, <i>P</i> = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, <i>P</i> = 0.090; mtDNA: 0.2 ± 0.4, <i>P</i> = 0.65).</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Graphical Abstract</h3>\",\"PeriodicalId\":19755,\"journal\":{\"name\":\"Pediatric Radiology\",\"volume\":\"51 1\",\"pages\":\"\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Radiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00247-024-06048-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Radiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00247-024-06048-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography – a prospective single-center study
Background
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.
Objective
Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography.
Materials and methods
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.
Results
No biomarker exhibited a dose-dependent response following radiation (γH2AX: R2 = 0.0012, P = 0.86; MMP: R2 = 0.016, P = 0.53; mtDNA: R2 = 0.10, P = 0.11; ROS: R2 = 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).
Conclusions
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.
期刊介绍：
Official Journal of the European Society of Pediatric Radiology, the Society for Pediatric Radiology and the Asian and Oceanic Society for Pediatric Radiology
Pediatric Radiology informs its readers of new findings and progress in all areas of pediatric imaging and in related fields. This is achieved by a blend of original papers, complemented by reviews that set out the present state of knowledge in a particular area of the specialty or summarize specific topics in which discussion has led to clear conclusions. Advances in technology, methodology, apparatus and auxiliary equipment are presented, and modifications of standard techniques are described.
Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.
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