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Evaluation of methemoglobin as an intravascular contrast agent: T1 relaxation time effect in a rabbit model
Seong-Eun Kim1, J Scott McNally1, Matthew D Alexander1
1Utah Center for Advanced Imaging Research, Department of Radiology, University of Utah, Salt Lake City, UT, USA.
Objective:
Alternative contrast agents for MRI are needed for individuals who may respond adversely to gadolinium, and need an intravascular agent for specific indications. One potential contrast agent is intracellular methemoglobin, a paramagnetic molecule that is normally present in small amounts in red blood cells. An animal model was used to determine whether methemoglobin modulation with intravenous sodium nitrite transiently changes the T1 relaxation of blood.
Methods:
Four adult New Zealand white rabbits were treated with 30 mg intravenous sodium nitrite. 3D TOF and 3D MPRAGE images were acquired before (baseline) and after methemoglobin modulation. T1 of blood was measured with 2D ss EPl acquisitions with inversion recovery preparation performed at two-minute intervals up to 30 min. T1 maps were calculated by fitting the signal recovery curve within major blood vessels.
Results:
Baseline T1 was 1758 ± 53 ms in carotid arteries and 1716 ± 41 ms in jugular veins. Sodium nitrite significantly changed intravascular T1 relaxation. The mean minimum value of T1 was 1126 ± 28 ms in carotid arteries 8 to 10 min after the injection of sodium nitrite. The mean minimum value of T1 was 1171 ± 52 ms in jugular veins 10 to 14 min after the injection of sodium nitrite. Arterial and venous T1 recovered to baseline after a period of 30 min.
Conclusion:
Methemoglobin modulation produces intravascular contrast on T1-weighted MRI in vivo. Additional studies are needed to safely optimize methemoglobin modulation and sequence parameters for maximal tissue contrast.
Insights
Intravascular methemoglobin modulation using sodium nitrite transiently alters blood T1 relaxation times. This finding suggests potential for methemoglobin as an alternative MRI contrast agent, particularly for patients sensitive to gadolinium.
Area of Science:
- Medical Imaging
- Biochemistry
- Pharmacology
Background:
- Gadolinium-based contrast agents (GBCAs) carry risks for certain patients.
- Intravascular contrast agents are needed for specific MRI applications.
- Methemoglobin, an intracellular paramagnetic molecule, is a potential alternative contrast agent.
Purpose of the Study:
- To investigate if intravenous sodium nitrite can modulate methemoglobin levels.
- To determine the effect of methemoglobin modulation on blood T1 relaxation time in vivo.
- To assess the potential of methemoglobin as an intravascular MRI contrast agent.
Main Methods:
- New Zealand white rabbits received intravenous sodium nitrite.
- 3D Time-of-Flight (TOF) and 3D MPRAGE MRI sequences were acquired.
- Blood T1 relaxation times were measured using 2D steady-state echo-planar imaging (EPI) with inversion recovery.
Main Results:
- Sodium nitrite significantly reduced blood T1 relaxation times in carotid arteries and jugular veins.
- T1 values decreased from baseline (approx. 1700 ms) to a minimum of ~1100-1200 ms post-injection.
- Blood T1 relaxation times returned to baseline levels within 30 minutes.
Conclusions:
- Methemoglobin modulation with sodium nitrite creates intravascular contrast on T1-weighted MRI.
- This technique shows promise as an alternative to gadolinium-based contrast agents.
- Further research is required to optimize parameters for maximal tissue contrast.

