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Published on: June 7, 2024
Mapping of cerebral oxidative metabolism with MRI
Eric A Mellon1, R Shashank Beesam, Mark A Elliott
1Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Abstract:
Using a T(1rho) MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9% + or - 2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T(1rho) MRI following administration of gas. Metabolism was calculated from the change in the T(1rho) weighted MRI signal due to H(2)(17)O generated from inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H(2)(17)O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive gas. Given the demonstrated high efficiency in use of and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.
Insights
This study shows a new MRI method to detect brain oxygen metabolism in large animals, using minimal gas. This technique, T(1rho) MRI, can be adapted for human studies of metabolic disorders.
Area of Science:
- Medical Imaging
- Metabolic Research
- Neuroscience
Background:
- Cerebral oxidative metabolism is crucial for brain function.
- Current methods for measuring metabolism often require significant gas utilization or are invasive.
- Developing non-invasive techniques for assessing brain metabolism is essential for understanding and treating metabolic derangements.
Purpose of the Study:
- To demonstrate a T(1rho) MRI-based indirect detection method for cerebral oxidative metabolism.
- To assess the modulation of cerebral metabolism by a mitochondrial uncoupling agent (2,4-dinitrophenol, DNP).
- To validate the technique in a large animal model with human-comparable lung capacity, minimizing gas usage.
Main Methods:
- Utilized T(1rho) MRI for indirect detection of cerebral oxidative metabolism in swine.
- Administered 2,4-dinitrophenol (DNP) to modulate metabolic activity.
- Measured metabolic changes via exhaled gas analysis and T(1rho) MRI signal changes related to H(2)(17)O.
- Confirmed results using oxygen-17 MR spectroscopy.
Main Results:
- Demonstrated successful detection of cerebral oxidative metabolism using T(1rho) MRI.
- Showed that DNP administration increased whole-body metabolism by 11.9% ± 2.5% per mg/kg.
- Validated T(1rho) MRI findings with oxygen-17 MR spectroscopy, confirming in vivo H(2)(17)O measurements.
- Achieved these measurements with minimal utilization of expensive gases.
Conclusions:
- Indirect oxygen-17 imaging via T(1rho) MRI can effectively detect and modulate oxygen metabolism in a large animal model.
- The technique is feasible on standard clinical MRI scanners with high efficiency in gas use.
- This approach enables the adaptation of T(1rho) MRI for human studies investigating various metabolic disorders.
