Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography - a prospective single-center study

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

Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography - a prospective single-center study

Pediatr Radiol. 2024 Oct;54(11):1906-1918. doi: 10.1007/s00247-024-06048-7. Epub 2024 Sep 17.

Authors

Kaley A Hogarth^{1

2}, Nicholas A Shkumat^{3

4}, Simal Goman³, Afsaneh Amirabadi³, Suzanne Bickford^{3

5}, Prakash Muthusami^{3

4

5}, Bairbre L Connolly^{6

7

8}, Jason T Maynes^{9

10

11

12}

Affiliations

¹ Program in Molecular Medicine, SickKids Research Institute, Toronto, ON, Canada. kaley.hogarth@sickkids.ca.
² Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada. kaley.hogarth@sickkids.ca.
³ Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, Toronto, ON, Canada.
⁴ Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
⁵ Paediatric Neurovascular Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁶ Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, Toronto, ON, Canada. bairbre.connolly@sickkids.ca.
⁷ Department of Medical Imaging, University of Toronto, Toronto, ON, Canada. bairbre.connolly@sickkids.ca.
⁸ Medical Imaging, Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada. bairbre.connolly@sickkids.ca.
⁹ Program in Molecular Medicine, SickKids Research Institute, Toronto, ON, Canada. jason.maynes@sickkids.ca.
¹⁰ Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada. jason.maynes@sickkids.ca.
¹¹ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. jason.maynes@sickkids.ca.
¹² Department of Biochemistry, University of Toronto, Toronto, ON, Canada. jason.maynes@sickkids.ca.

PMID: 39285018
DOI: 10.1007/s00247-024-06048-7

Abstract

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.

Keywords: Biomarkers; H2A histone family member X (H2AX); Interventional radiology; Ionizing radiation; Mitochondria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Biomarkers* / blood
Cerebral Angiography / methods
Child
Child, Preschool
DNA Damage*
DNA, Mitochondrial*
Dose-Response Relationship, Radiation
Female
Humans
Infant
Leukocytes, Mononuclear / metabolism
Male
Membrane Potential, Mitochondrial
Mitochondria
Prospective Studies
Reactive Oxygen Species / metabolism

Substances

Biomarkers
DNA, Mitochondrial
Reactive Oxygen Species