Anesthesia-related brain microstructure modulations detected by diffusion magnetic resonance imaging

Area of Science:

• Neuroscience
• Biophysics
• Medical Imaging

Background:

• Sleep and anesthesia induce significant changes in brain microstructure, particularly the extracellular space (ECS).
• Preclinical diffusion MRI (dMRI) commonly uses isoflurane anesthesia, necessitating an understanding of its microstructural effects.
• Diffusion kurtosis imaging (DKI) is sensitive to microstructural alterations in the brain.

Purpose of the Study:

• To investigate the impact of isoflurane anesthesia on brain microstructure using DKI in mice.
• To characterize the time course of anesthesia-induced microstructural changes.
• To assess the utility of DKI for studying conditions like brain edema.

Main Methods:

• Diffusion kurtosis imaging (DKI) was employed to assess brain microstructure in awake and isoflurane-anesthetized mice (n=22).
• Time-resolved fast DKI was developed and utilized to capture dynamic microstructural changes during anesthesia transitions (n=5).
• DKI was applied to a mouse model of brain edema (n=4) to evaluate its sensitivity to ECS volume reduction.

Main Results:

• Isoflurane anesthesia significantly decreased mean diffusivity (MD) and mean kurtosis (MK) in both gray and white matter (p < 0.001).
• Time-resolved DKI revealed rapid onset of these microstructural changes upon anesthesia delivery and slow normalization upon recovery.
• DKI detected microstructural alterations consistent with reduced ECS volume in the brain edema model.

Conclusions:

• Isoflurane anesthesia demonstrably affects DKI parameters and brain microstructure, primarily by reducing extracellular space volume.
• The observed microstructural changes are rapid and slow to reverse, with significant implications for preclinical dMRI studies.
• DKI methods are suitable for in-bore perturbation studies, including investigations into sleep/wake-dependent glymphatic system functions.