Ting Guo1, Vann Chau1, Shabnam Peyvandi2, Beatrice Latal3, Patrick S McQuillen4, Walter Knirsch5, Anne Synnes6, Maria Feldmann3, Nadja Naef3, M Mallar Chakravarty7, Alessandra De Petrillo8, Emma G Duerden1, A James Barkovich9, Steven P Miller10. 1. Neurosciences and Mental Health, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada. 2. Department of Pediatric Cardiology, Benioff Children's Hospital and University of California, San Francisco, CA, USA. 3. Child Development Center, University Children's Hospital, Zurich, Switzerland. 4. Department of Pediatrics, Benioff Children's Hospital and University of California, San Francisco, CA, USA. 5. Department of Pediatric Cardiology, University Children's Hospital, Zurich, Switzerland. 6. Department of Pediatrics, University of British Columbia, BC Children's Hospital Research Institute, Vancouver, BC, Canada. 7. Cerebral Imaging Centre, Douglas Mental Health Research Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada; Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada. 8. Neurosciences and Mental Health, The Hospital for Sick Children Research Institute, Toronto, ON, Canada. 9. Department of Radiology, Benioff Children's Hospital and University of California, San Francisco, CA, USA. 10. Neurosciences and Mental Health, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada. Electronic address: steven.miller@sickkids.ca.
Abstract
BACKGROUND: Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume. OBJECTIVE: (1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping. METHODS: In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks). RESULTS: The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm3, IQR = 26-174.7 mm3); UCSF (median = 104 mm3, IQR = 44-243 mm3); UCZ (median = 121 mm3, IQR = 68-200.8 mm3). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm3 increase of WMI per week decrease in gestational age; 95% CI 11.5-70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms. CONCLUSIONS: WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates.
BACKGROUND: Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume. OBJECTIVE: (1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping. METHODS: In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks). RESULTS: The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm3, IQR = 26-174.7 mm3); UCSF (median = 104 mm3, IQR = 44-243 mm3); UCZ (median = 121 mm3, IQR = 68-200.8 mm3). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm3 increase of WMI per week decrease in gestational age; 95% CI 11.5-70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms. CONCLUSIONS:WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates.
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