Bruce A Berkowitz1, Roberto Romero2, Robert H Podolsky3, Karen M Lins-Childers3, Yimin Shen4, Tilman Rosales5, Youssef Zaim Wadghiri6, D Minh Hoang6, Marcia Arenas-Hernandez7, Valeria Garcia-Flores7, George Schwenkel7, Bogdan Panaitescu7, Nardhy Gomez-Lopez8. 1. Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA. Electronic address: baberko@med.wayne.edu. 2. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, Maryland, 20847, and Detroit, Michigan, 48201, USA; Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan, 48109, USA; Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan, 48824, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, 48201, USA; Detroit Medical Center, Detroit, Michigan, 48201, USA. 3. Beaumont Research Institute, Beaumont Health, Royal Oak, Michigan, 48073, USA. 4. Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA. 5. Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA. 6. Department of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), Bernard and Irene Schwartz Center for Biomedical Imaging, NYU School of Medicine and NYU Langone Health, New York, New York, 10016, USA. 7. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, Maryland, 20847, and Detroit, Michigan, 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA. 8. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, Maryland, 20847, and Detroit, Michigan, 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA; Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA. Electronic address: nardhy.gomez-lopez@wayne.edu.
Abstract
PURPOSE: To achieve sufficient precision of R1 (=1/T1) maps of the fetal brain in utero to perform QUEnch-assiSTed (QUEST) MRI in which a significant anti-oxidant-induced reduction in R1 indicates oxidative stress. METHODS: C57BL/6 mouse fetuses in utero were gently and non-surgically isolated and secured using a homemade 3D printed clip. Using a commercial receive-only surface coil, brain maps of R1, an index sensitive to excessive and continuous free radical production, were collected using either a conventional Cartesian or a non-Cartesian (periodically rotated overlapping parallel lines with enhanced reconstruction) progressive saturation sequence. Data were normalized to the shortest TR time to remove bias. To assess oxidative stress, brain R1 maps were acquired on the lipopolysaccharide (LPS) model of preterm birth ± rosiglitazone (ROSI, which has anti-oxidant properties); phosphate buffered saline (PBS) controls ± ROSI were similarly studied. RESULTS: Sufficient quality R1 maps were generated by a combination of the 3D printed clip, surface coil detection, non-Cartesian sequence, and normalization scheme ensuring minimal fetal movement, good detection sensitivity, reduced motion artifacts, and minimal baseline variations, respectively. In the LPS group, the combined caudate-putamen and thalamus region R1 was reduced (p < 0.05) with ROSI treatment consistent with brain oxidative stress; no evidence for oxidative stress was found in the pons region. In the PBS control group, brain R1's did not change with ROSI treatment. CONCLUSION: The sensitivity and reproducibility of the combined approaches described herein enabled first-time demonstration of regional oxidative stress measurements of the fetal brain in utero using QUEST MRI.
PURPOSE: To achieve sufficient precision of R1 (=1/T1) maps of the fetal brain in utero to perform QUEnch-assiSTed (QUEST) MRI in which a significant anti-oxidant-induced reduction in R1 indicates oxidative stress. METHODS: C57BL/6 mouse fetuses in utero were gently and non-surgically isolated and secured using a homemade 3D printed clip. Using a commercial receive-only surface coil, brain maps of R1, an index sensitive to excessive and continuous free radical production, were collected using either a conventional Cartesian or a non-Cartesian (periodically rotated overlapping parallel lines with enhanced reconstruction) progressive saturation sequence. Data were normalized to the shortest TR time to remove bias. To assess oxidative stress, brain R1 maps were acquired on the lipopolysaccharide (LPS) model of preterm birth ± rosiglitazone (ROSI, which has anti-oxidant properties); phosphate buffered saline (PBS) controls ± ROSI were similarly studied. RESULTS: Sufficient quality R1 maps were generated by a combination of the 3D printed clip, surface coil detection, non-Cartesian sequence, and normalization scheme ensuring minimal fetal movement, good detection sensitivity, reduced motion artifacts, and minimal baseline variations, respectively. In the LPS group, the combined caudate-putamen and thalamus region R1 was reduced (p < 0.05) with ROSI treatment consistent with brain oxidative stress; no evidence for oxidative stress was found in the pons region. In the PBS control group, brain R1's did not change with ROSI treatment. CONCLUSION: The sensitivity and reproducibility of the combined approaches described herein enabled first-time demonstration of regional oxidative stress measurements of the fetal brain in utero using QUEST MRI.
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