Nara S Higano1,2,3,4,5, Xuefeng Cao6,7, Jinbang Guo6,8, Xiaojie Wang9, Christopher D Kroenke9, Alyssa L Filuta10, James P Bridges10,11, Jason C Woods6,12,8,13,14,7. 1. Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children's Hospital, Cincinnati, OH, USA. nara.higano@cchmc.org. 2. Bronchopulmonary Dysplasia Center, Cincinnati Children's Hospital, Cincinnati, OH, USA. nara.higano@cchmc.org. 3. Division of Pulmonary Medicine, Cincinnati Children's Hospital, Cincinnati, OH, USA. nara.higano@cchmc.org. 4. Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. nara.higano@cchmc.org. 5. Department of Radiology, Cincinnati Children's Hospital, Cincinnati, OH, USA. nara.higano@cchmc.org. 6. Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children's Hospital, Cincinnati, OH, USA. 7. Department of Physics, University of Cincinnati, Cincinnati, OH, USA. 8. Division of Pulmonary Medicine, Cincinnati Children's Hospital, Cincinnati, OH, USA. 9. Division of Neuroscience, Oregon National Primate Research Center and Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA. 10. Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, OH, USA. 11. Department of Medicine, National Jewish Health, Denver, CO, USA. 12. Bronchopulmonary Dysplasia Center, Cincinnati Children's Hospital, Cincinnati, OH, USA. 13. Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. 14. Department of Radiology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
Abstract
OBJECTIVE: To demonstrate sensitivity of diffusion-weighted MRI (DW-MRI) to pulmonary cellular-space changes during normal in utero development using fetal rhesus macaques, compared to histological biomarkers. STUDY DESIGN: In vivo/ex vivo DW-MRI was acquired in 26 fetal rhesus lungs (early-canalicular through saccular stages). Apparent diffusion coefficients (ADC) from MRI and tissue area density (H&E), alveolar type-II cells (ABCA3), and epithelial cells (TTF1) from histology were compared between gestational stages. RESULTS: In vivo/ex vivo ADC correlated with each other (Spearman ρ = 0.47, P = 0.038; Bland-Altman bias = 0.0835) and with area-density (in vivo ρ = -0.56, P = 0.011; ex vivo ρ = -0.83, P < 0.0001). In vivo/ex vivo ADC increased exponentially toward saturation with gestational stage (R2 = 0.49/0.49), while area-density decreased exponentially (R2 = 0.53). ABCA3 and TTF1 stains demonstrated expected fetal cellular development. CONCLUSIONS: Fetal DW-MRI provides a non-invasive biomarker for pulmonary structural maturation, with a strong correlation to histological markers during tissue development in rhesus macaques. This method has strong potential for assessing human fetal development, particularly in patients with pulmonary hypoplasia.
OBJECTIVE: To demonstrate sensitivity of diffusion-weighted MRI (DW-MRI) to pulmonary cellular-space changes during normal in utero development using fetal rhesus macaques, compared to histological biomarkers. STUDY DESIGN: In vivo/ex vivo DW-MRI was acquired in 26 fetal rhesus lungs (early-canalicular through saccular stages). Apparent diffusion coefficients (ADC) from MRI and tissue area density (H&E), alveolar type-II cells (ABCA3), and epithelial cells (TTF1) from histology were compared between gestational stages. RESULTS: In vivo/ex vivo ADC correlated with each other (Spearman ρ = 0.47, P = 0.038; Bland-Altman bias = 0.0835) and with area-density (in vivo ρ = -0.56, P = 0.011; ex vivo ρ = -0.83, P < 0.0001). In vivo/ex vivo ADC increased exponentially toward saturation with gestational stage (R2 = 0.49/0.49), while area-density decreased exponentially (R2 = 0.53). ABCA3 and TTF1 stains demonstrated expected fetal cellular development. CONCLUSIONS: Fetal DW-MRI provides a non-invasive biomarker for pulmonary structural maturation, with a strong correlation to histological markers during tissue development in rhesus macaques. This method has strong potential for assessing human fetal development, particularly in patients with pulmonary hypoplasia.
Authors: Vanessa A Jimenez; Xiaojie Wang; Natali Newman; Nicole A R Walter; Steven Gonzales; Jamie O Lo; Mathew M Ford; Verginia C Cuzon Carlson; Kathleen A Grant; Christopher D Kroenke Journal: Alcohol Clin Exp Res Date: 2019-01-11 Impact factor: 3.455
Authors: Lauren M Yoder; Nara S Higano; Andrew H Schapiro; Robert J Fleck; Erik B Hysinger; Alister J Bates; Paul S Kingma; Stephanie L Merhar; Sean B Fain; Jason C Woods Journal: Pediatr Pulmonol Date: 2019-05-27