(89b) Comparison of Methemoglobin and Deoxyhemoglobin As Potential Contrast Agents in Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging (MRI) is a valuable tool for the diagnosis of a patients’ health condition. Contrast agents, which are paramagnetic, are used to enhance the signal intensity (brightness) of the image. Gadolinium-based contrast agents are broadly used due to their effective ability to enhance the MRI signal intensity. However, concerns about the limitations and safety of gadolinium-based contrast agents, such as accumulation in tissues, have led to an interest in alternative contrast agents.

Methemoglobin and deoxyhemoglobin are naturally occurring blood species that have the potential to be used as contrast agent due to their paramagnetic properties. Previous studies in humans (deoxyhemoglobin) and dogs (methemoglobin) have shown that these two species can effectively enhance MRI signal intensities. However, it is unknown as to which of these species has the better ability to be used as a contrast agent. Methemoglobin is typically 1-2% of the total hemoglobin. It has been shown that up to 20% of methemoglobin can be tolerated. Methemoglobin can be produced via the addition of nitric oxide (NO) or nitrite.

This work involved the development and analysis of a NO-delivery system to rapidly produce methemoglobin. The system could also produce deoxyhemoglobin. Methemoglobin was produced by exposing oxyhemoglobin to NO using gas permeable tubes. Deoxyhemoglobin was produced by eliminating oxygen in the head space of a blood reservoir to force oxygen to be removed from the blood. Results showed that methemoglobin is essentially the only product produced during NO delivery until near complete conversion of oxyhemoglobin to methemoglobin. Methemoglobin is stable if NO delivery is removed at this point. However, if NO delivery is continued after making methemoglobin, nitrosylhemoglobin species are also produced.

As methemoglobin or deoxyhemoglobin were made, samples were analyzed with an MRI. The T1-weighted measurements were obtained for these samples. In some cases, a mixture of methemoglobin and nitrosylhemoglobin were also analyzed for the TI-weighted measurements. The T1 values were compared among the various studies to identify which blood species had the best potential to be used as a contrast agent. Initial studies have shown that methemoglobin is the most viable hemoglobin-based candidate to be used as a contrast agent.