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Updated: Dec 25, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Cytosolic diffusivity and microscopic anisotropy of N-acetyl aspartate in human white matter with diffusion-weighted
Henrik Lundell1, Carson Ingo2,3, Tim B Dyrby1,4
1Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark.
Abstract:
Metabolite diffusion measurable in humans in vivo with diffusion-weighted spectroscopy (DW-MRS) provides a window into the intracellular morphology and state of specific cell types. Anisotropic diffusion in white matter is governed by the microscopic properties of the individual cell types and their structural units (axons, soma, dendrites). However, anisotropy is also markedly affected by the macroscopic orientational distribution over the imaging voxel, particularly in DW-MRS, where the dimensions of the volume of interest (VOI) are much larger than those typically used in diffusion-weighted imaging. One way to address the confound of macroscopic structural features is to average the measurements acquired with uniformly distributed gradient directions to mimic a situation where fibers present in the VOI are orientationally uniformly distributed. This situation allows the extraction of relevant microstructural features such as transverse and longitudinal diffusivities within axons and the related microscopic fractional anisotropy. We present human DW-MRS data acquired at 7 T in two different white matter regions, processed and analyzed as described above, and find that intra-axonal diffusion of the neuronal metabolite N-acetyl aspartate is in good correspondence to simple model interpretations, such as multi-Gaussian diffusion from disperse fibers where the transverse diffusivity can be neglected. We also discuss the implications of our approach for current and future applications of DW-MRS for cell-specific measurements.
Insights
Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) measures metabolite diffusion in vivo. Averaging diffusion data reveals intra-axonal diffusion of N-acetyl aspartate in white matter, correlating with microstructural models.
Area of Science:
- Neuroimaging
- Biophysics
- Cellular Biology
Background:
- Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers insights into intracellular morphology and cell states.
- Anisotropic diffusion in white matter is influenced by both microscopic cell properties and macroscopic voxel orientation distributions.
- DW-MRS voxel dimensions can exacerbate macroscopic orientation effects compared to diffusion-weighted imaging.
Purpose of the Study:
- To develop and validate a method for analyzing DW-MRS data that accounts for macroscopic orientational distributions.
- To extract microstructural features like intra-axonal diffusivities and microscopic fractional anisotropy.
- To investigate the intra-axonal diffusion of N-acetyl aspartate in human white matter.
Main Methods:
- Acquisition of human DW-MRS data at 7 Tesla in two white matter regions.
- Processing and analysis of data by averaging measurements from uniformly distributed gradient directions.
- Application of a multi-Gaussian diffusion model to interpret results, neglecting transverse diffusivity.
Main Results:
- The proposed averaging method allows for the extraction of microstructural features from DW-MRS data.
- Intra-axonal diffusion of N-acetyl aspartate in human white matter aligns well with simplified diffusion models.
- The findings support the utility of the approach for understanding axonal diffusion.
Conclusions:
- Averaging DW-MRS data mitigates macroscopic orientation confounds, enabling microstructural analysis.
- The study validates the interpretation of intra-axonal N-acetyl aspartate diffusion using basic models.
- This approach has significant implications for cell-specific measurements using DW-MRS.
