MR Imaging-derived Oxygen- Hemoglobin dissociation curves and Fetal-Placental Oxygen- Hemoglobin affinities

Reut Avni, Ofra Golani, Ayelet Akselrod-Ballin, Yonni Cohen, Inbal Biton, Joel R. Garbow, Michal Neeman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Purpose: To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetalplacental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2∗ and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods: All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of threedimensional gradient-echo T2∗- And T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2∗ values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2∗divided by R2∗at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2∗ divided by R2∗at baseline scaled (y) equals 0.5. Results: The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P , .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003). Reproduction of the MR imaging-based oxygenhemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion: MR imaging-based oxygen-hemoglobin dissociation curves and oxygen-hemoglobin affinity information were derived for pregnant mice by using 9.4-T MR imaging, which suggests a potential to overcome the need for direct sampling of fetal or maternal blood.

Original languageEnglish
Pages (from-to)68-77
Number of pages10
JournalRadiology
Volume280
Issue number1
DOIs
StatePublished - Jul 2016
Externally publishedYes

Funding

FundersFunder number
National Institute of Child Health and Human Development
National Institutes of Health
European Commission
Seventh Framework Programme232640
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentR01HD086323

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