Ante Zhu1, Scott B Reeder2, Kevin M Johnson3, Sydney M Nguyen4, Sean B Fain5, Ian M Bird6, Thaddeus G Golos7, Oliver Wieben3, Dinesh M Shah6, Diego Hernando8. 1. Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Department of Radiology, University of Wisconsin, Madison, WI, USA. 2. Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Department of Radiology, University of Wisconsin, Madison, WI, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA; Department of Medicine, University of Wisconsin, Madison, WI, USA; Department of Emergency Medicine, University of Wisconsin, Madison, WI, USA. 3. Department of Radiology, University of Wisconsin, Madison, WI, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA. 4. Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA; Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA. 5. Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Department of Radiology, University of Wisconsin, Madison, WI, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA. 6. Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA. 7. Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA; Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA; Department of Comparative Biosciences, University of Wisconsin, Madison, WI, USA. 8. Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Department of Radiology, University of Wisconsin, Madison, WI, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA; Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI, USA. Electronic address: dhernando@wisc.edu.
Abstract
OBJECTIVES: To assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model. MATERIALS AND METHODS: In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test. RESULTS: In fetuses, a slope of 0.3 s-1/day (P = 0.008), 0.00 ppm/day (P = 0.699) and - 0.2 s-1/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. CONCLUSIONS: This work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.
OBJECTIVES: To assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model. MATERIALS AND METHODS: In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test. RESULTS: In fetuses, a slope of 0.3 s-1/day (P = 0.008), 0.00 ppm/day (P = 0.699) and - 0.2 s-1/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. CONCLUSIONS: This work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.
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