Related Experiment Video
Updated: May 9, 2025
Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo
Published on: June 28, 2019
In Vivo Quantification of Creatine Kinase Kinetics in Mouse Brain Using 31P-MRS at 7 T
Mohamed Tachrount1, Sean Smart1, Jason Lerch1,2,3
1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Abstract:
31P-MRS is a method of choice for studying neuroenergetics in vivo, but its application in the mouse brain has been limited, often restricted to ultrahigh field (> 7 T) MRI scanners. Establishing its feasibility on more readily available preclinical 7-T scanners would create new opportunities to study metabolism and physiology in murine models of brain disorders. Here, we demonstrate that the apparent forward rate constant (kf) of creatine kinase (CK) can be accurately quantified using a progressive saturation-transfer approach in the mouse brain at 7 T. We also find that a 20% reduction in respiration of anesthetized mice can lead to 36% increase in kf attributable to a drop in cellular pH and mitochondrial ATP production. To achieve this, we used a test-retest analysis to assess the reliability and repeatability of 31P-MRS acquisition, analysis, and experimental design protocols. We report that many 31P-containing metabolites can be reliably measured using a localized 3D-ISIS sequence, which showed highest SNR amplitude, SNR consistency, and minimal T2 relaxation signal loss. Our study identifies key physiological factors influencing mouse brain energy homeostasis in vivo and provides a methodological basis to guide future studies interested in implementing 31P-MRS on preclinical 7-T scanners.
Insights
Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) can now reliably study mouse brain energetics at 7T. This method reveals how respiration changes impact brain energy metabolism, offering new insights into neurological disorders.
Area of Science:
- Neuroscience
- Biophysics
- Biochemistry
Background:
- 31P-MRS is crucial for in vivo neuroenergetics research.
- Previous applications in mouse brains were limited to ultrahigh field MRI scanners (>7T).
- Adapting 31P-MRS for preclinical 7T scanners expands research capabilities for brain disorders.
Purpose of the Study:
- To establish the feasibility of quantifying creatine kinase (CK) forward rate constant (kf) using 31P-MRS in the mouse brain at 7T.
- To assess the impact of physiological changes, such as reduced respiration, on mouse brain energy homeostasis.
- To validate the reliability and repeatability of 31P-MRS protocols for in vivo mouse brain studies.
Main Methods:
- Utilized a progressive saturation-transfer approach to measure CK kf at 7T.
- Employed a localized 3D-ISIS sequence for 31P-MRS acquisition, optimizing signal-to-noise ratio (SNR) and minimizing relaxation losses.
- Conducted test-retest analysis to evaluate the reliability of the MRS protocols.
Main Results:
- Successfully quantified CK kf in the mouse brain at 7T.
- Demonstrated that a 20% reduction in respiration increased kf by 36%, linked to decreased cellular pH and mitochondrial ATP production.
- Identified 3D-ISIS as a reliable sequence for measuring 31P-containing metabolites with high SNR and consistency.
Conclusions:
- 31P-MRS is a viable method for studying mouse brain energy metabolism on preclinical 7T scanners.
- Physiological factors like respiration significantly influence brain energy homeostasis.
- This study provides a methodological foundation for future research on murine models of brain disorders using 7T 31P-MRS.
