Julie Coloigner1,2, Chau Vu3, Matthew Borzage4,5, Adam Bush6, Soyoung Choi7, Xin Miao3, Yaqiong Chai1,3, Cristina Galarza8, Natasha Lepore1,3,5, Benita Tamrazi9, Thomas D Coates10,11, John C Wood3,12. 1. CIBORG Laboratory, Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California, USA. 2. Univ Rennes, CNRS, Inria, Inserm, IRISA UMR 6074, Rennes, France. 3. Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA. 4. Division of Neonatology, Fetal and Neonatal Institute, Children's Hospital Los Angeles, Los Angeles, California, USA. 5. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 6. Department of Radiology and Department of Electrical Engineering, Stanford University, Stanford, California, USA. 7. Neuroscience Graduate Program, University of Southern California, Los Angeles, California, USA. 8. Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 9. Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California, USA. 10. Division of Hematology-Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA. 11. Department of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 12. Division of Cardiology, Department of Pediatrics and Radiology, Children's Hospital Los Angeles, Los Angeles, California, USA.
Abstract
BACKGROUND: Obstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk. PURPOSE: To investigate the cerebral dynamic response to induced desaturation in SCD patients with and without SCI, chronic anemia, and healthy subjects. STUDY TYPE: Prospective. SUBJECTS: Twenty-six SCD patients (age = 21 ± 8.2, female 46.2%), including 15 subjects without SCI and nine subjects with SCI, 15 nonsickle anemic patients (age = 22 ± 5.8, female 66.7%), and 31 controls (age = 28 ± 12.3, female 77.4%). FIELD STRENGTH/SEQUENCE: 3T, gradient-echo echo-planar imaging. ASSESSMENT: A transient hypoxia challenge of five breaths of 100% nitrogen gas was performed with blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS) acquisitions. Hypoxia responses were characterized by desaturation depth, time-to-peak, return-to-baseline half-life, and posthypoxia recovery in the BOLD and NIRS time courses. SCI were documented by T2 fluid-attenuation inversion recovery (FLAIR). STATISTICAL TESTS: Univariate and multivariate regressions were performed between hypoxic parameters and anemia predictors. Voxelwise two-sample t-statistic maps were used to assess the regional difference in hypoxic responses between anemic and control groups. RESULTS: Compared to controls, SCD and chronically anemic patients demonstrated significantly higher desaturation depth (P < 0.01) and shorter return-to-baseline timing response (P < 0.01). Patients having SCI had shorter time-to-peak (P < 0.01), return-to-baseline (P < 0.01), and larger desaturation depth (P < 0.01) in both white matter regions at risk and normal-appearing white matter than patients without infarcts. On multivariate analysis, desaturation depth and timing varied with age, sex, blood flow, white blood cells, and cell-free hemoglobin (r2 = 0.25 for desaturation depth; r2 = 0.18 for time-to-peak; r2 = 0.37 for return-to-baseline). DATA CONCLUSION: Transient hypoxia revealed global and regional response differences between anemic and healthy subjects. SCI was associated with extensive heterogeneity of desaturation dynamics, consistent with extensive underlying microvascular remodeling.
BACKGROUND: Obstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk. PURPOSE: To investigate the cerebral dynamic response to induced desaturation in SCDpatients with and without SCI, chronic anemia, and healthy subjects. STUDY TYPE: Prospective. SUBJECTS: Twenty-six SCDpatients (age = 21 ± 8.2, female 46.2%), including 15 subjects without SCI and nine subjects with SCI, 15 nonsickle anemicpatients (age = 22 ± 5.8, female 66.7%), and 31 controls (age = 28 ± 12.3, female 77.4%). FIELD STRENGTH/SEQUENCE: 3T, gradient-echo echo-planar imaging. ASSESSMENT: A transient hypoxia challenge of five breaths of 100% nitrogen gas was performed with blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS) acquisitions. Hypoxia responses were characterized by desaturation depth, time-to-peak, return-to-baseline half-life, and posthypoxia recovery in the BOLD and NIRS time courses. SCI were documented by T2 fluid-attenuation inversion recovery (FLAIR). STATISTICAL TESTS: Univariate and multivariate regressions were performed between hypoxic parameters and anemia predictors. Voxelwise two-sample t-statistic maps were used to assess the regional difference in hypoxic responses between anemic and control groups. RESULTS: Compared to controls, SCD and chronically anemicpatients demonstrated significantly higher desaturation depth (P < 0.01) and shorter return-to-baseline timing response (P < 0.01). Patients having SCI had shorter time-to-peak (P < 0.01), return-to-baseline (P < 0.01), and larger desaturation depth (P < 0.01) in both white matter regions at risk and normal-appearing white matter than patients without infarcts. On multivariate analysis, desaturation depth and timing varied with age, sex, blood flow, white blood cells, and cell-free hemoglobin (r2 = 0.25 for desaturation depth; r2 = 0.18 for time-to-peak; r2 = 0.37 for return-to-baseline). DATA CONCLUSION: Transient hypoxia revealed global and regional response differences between anemic and healthy subjects. SCI was associated with extensive heterogeneity of desaturation dynamics, consistent with extensive underlying microvascular remodeling.
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