Rapid Formation of Methemoglobin via Nitric Oxide Delivery for Potential Use as an MRI Contrast Agent

Contrast-enhanced magnetic resonance angiography is a vital tool for evaluating vascular pathology. However, concerns about the limitations and safety of gadolinium-based contrast agents have led to an interest in alternative agents. Methemoglobin (metHb) increases the T1-weighted signal intensity o...

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Bibliographic Details
Published in:Annals of biomedical engineering 2023-03, Vol.51 (3), p.506-516
Main Authors: Markwalter, Denton J., Primavera, Kyle D., Day, Ronald W., Lewis, Randy S.
Format: Article
Language:English
Subjects:
Angiography
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Biophysics
Blood
Classical Mechanics
Contrast agents
Contrast Media
Conversion
Cytochrome b5
Cytochromes
Gadolinium
Hemoglobin
Hemoglobins
Magnetic Resonance Imaging
Methemoglobin
Nitric Oxide
Original Article
Oxyhemoglobin
Reductases
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Summary:Contrast-enhanced magnetic resonance angiography is a vital tool for evaluating vascular pathology. However, concerns about the limitations and safety of gadolinium-based contrast agents have led to an interest in alternative agents. Methemoglobin (metHb) increases the T1-weighted signal intensity of the magnetic resonance image of blood and could provide a safe and effective alternative. MetHb can be produced by the reaction of nitric oxide (NO) gas with oxyhemoglobin followed by natural conversion back to hemoglobin by cytochrome b5 reductase. Since rapid production of metHb via NO has not been studied, the effectiveness of producing metHb via NO delivery to blood was evaluated using a hollow-fiber module. MetHb production began immediately and > 90% conversion was achieved within 10 min. MetHb remained stable for at least 90 min when NO delivery was removed following metHb formation. Comparison of experimental data for metHb formation with model predictions showed that only a fraction of the NO delivered was utilized for metHb production, suggesting an additional fast reaction of NO with other blood constituents. Directly delivering NO to blood for the rapid formation of metHb provides a potential platform for producing metHb as an alternative contrast agent.
ISSN:0090-6964
1573-9686
DOI:10.1007/s10439-022-03049-1