Establishing upper limits on neuronal activity-evoked pH changes with APT-CEST MRI at 7 T

Area of Science:

• Neuroimaging
• Biophysics
• Magnetic Resonance Imaging

Background:

• Neuronal activity is associated with metabolic changes that can affect local brain pH.
• Amide proton transfer-chemical exchange saturation transfer (APT-CEST) MRI is a promising technique for detecting pH variations in vivo.
• High-field MRI (7 Tesla) offers increased sensitivity for detecting subtle physiological changes.

Purpose of the Study:

• To evaluate the feasibility of using 7 Tesla APT-CEST MRI to detect neuronal activity-evoked pH changes.
• To optimize an APT-CEST sequence for enhanced pH sensitivity.
• To assess the magnitude of pH changes in the visual cortex during visual stimulation.

Main Methods:

• A 3D APT-CEST sequence was optimized using Bloch-McConnell equations for 7T MRI.
• pH sensitivity was validated in phantoms and simulated data.
• In three healthy subjects, visual stimuli were employed to evoke transient pH changes, with data acquired every 12.6 seconds.

Main Results:

• Theoretical analysis indicated a potential pH change of 0.03 could be detected.
• Despite optimized sequences and stimuli, only blood oxygenation level-dependent (BOLD) effects were observed in the visual cortex.
• No significant pH changes were discernible during visual stimulation experiments.

Conclusions:

• Transient brain pH changes in response to visual stimuli, if they occur, are likely less than 0.03 pH units.
• Current APT-CEST MRI techniques face significant challenges in detecting such small pH variations.
• Further advancements in MRI technology and analysis methods are needed to reliably measure activity-dependent pH shifts in the brain.