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Updated: Jul 16, 2025
Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging
Published on: November 8, 2012
Anesthesia-related brain microstructure modulations detected by diffusion magnetic resonance imaging
Thomas Beck Lindhardt1,2,3, Christian Stald Skoven1, Luca Bordoni4,5
1Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Abstract:
Recent studies have shown significant changes to brain microstructure during sleep and anesthesia. In vivo optical microscopy and magnetic resonance imaging (MRI) studies have attributed these changes to anesthesia and sleep-related modulation of the brain's extracellular space (ECS). Isoflurane anesthesia is widely used in preclinical diffusion MRI (dMRI) and it is therefore important to investigate if the brain's microstructure is affected by anesthesia to an extent detectable with dMRI. Here, we employ diffusion kurtosis imaging (DKI) to assess brain microstructure in the awake and anesthetized mouse brain (n = 22). We find both mean diffusivity (MD) and mean kurtosis (MK) to be significantly decreased in the anesthetized mouse brain compared with the awake state (p < 0.001 for both). This effect is observed in both gray matter and white matter. To further investigate the time course of these changes we introduce a method for time-resolved fast DKI. With this, we show the time course of the microstructural alterations in mice (n = 5) as they transition between states in an awake-anesthesia-awake paradigm. We find that the decrease in MD and MK occurs rapidly after delivery of gas isoflurane anesthesia and that values normalize only slowly when the animals return to the awake state. Finally, time-resolved fast DKI is employed in an experimental mouse model of brain edema (n = 4), where cell swelling causes the ECS volume to decrease. Our results show that isoflurane affects DKI parameters and metrics of brain microstructure and point to isoflurane causing a reduction in the ECS volume. The demonstrated DKI methods are suitable for in-bore perturbation studies, for example, for investigating microstructural modulations related to sleep/wake-dependent functions of the glymphatic system. Importantly, our study shows an effect of isoflurane anesthesia on rodent brain microstructure that has broad relevance to preclinical dMRI.
Insights
Isoflurane anesthesia significantly alters brain microstructure, decreasing mean diffusivity (MD) and mean kurtosis (MK) detectable by diffusion kurtosis imaging (DKI). These changes occur rapidly and resolve slowly, impacting preclinical diffusion MRI (dMRI) research.
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.
