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Searching for the Neurite Density with Diffusion MRI: Challenges for Biophysical Modeling

Institution:
Clinical Sciences Lund, Medical Radiation Physics, Lund University, Lund, Sweden.
Publisher:
Wiley
Publication Date:
Jun-2019
Journal:
Hum Brain Mapp
Volume Number:
40
Issue Number:
8
Pages:
2529-45
Citation:
Hum Brain Mapp. 2019 Jun 1;40(8):2529-45.
PubMed ID:
30802367
PMCID:
PMC6503974
Keywords:
anisotropy, axons, dendrites, diffusion MRI, myelin, neurites
Appears in Collections:
NAC, LMI, NCIGT, SPL
Sponsors:
AM13-0090//Stiftelsen för Strategisk Forskning
2016-03443//Vetenskapsrådet
349-2007-869//Vetenskapsrådet
P41 EB015898//National Institutes of Health
P41 EB015902//National Institutes of Health
R01MH074794//National Institutes of Health
MN15//Random Walk Imaging
Generated Citation:
Lampinen B., Szczepankiewicz F., Novén M., van Westen D., Hansson O., Englund E., Mårtensson J., Westin C-F., Nilsson M. Searching for the Neurite Density with Diffusion MRI: Challenges for Biophysical Modeling. Hum Brain Mapp. 2019 Jun 1;40(8):2529-45. PMID: 30802367. PMCID: PMC6503974.
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In vivo mapping of the neurite density with diffusion MRI (dMRI) is a high but challenging aim. First, it is unknown whether all neurites exhibit completely anisotropic ("stick-like") diffusion. Second, the "density" of tissue components may be confounded by non-diffusion properties such as T2 relaxation. Third, the domain of validity for the estimated parameters to serve as indices of neurite density is incompletely explored. We investigated these challenges by acquiring data with "b-tensor encoding" and multiple echo times in brain regions with low orientation coherence and in white matter lesions. Results showed that microscopic anisotropy from b-tensor data is associated with myelinated axons but not with dendrites. Furthermore, b-tensor data together with data acquired for multiple echo times showed that unbiased density estimates in white matter lesions require data-driven estimates of compartment-specific T2 values. Finally, the "stick" fractions of different biophysical models could generally not serve as neurite density indices across the healthy brain and white matter lesions, where outcomes of comparisons depended on the choice of constraints. In particular, constraining compartment-specific T2 values was ambiguous in the healthy brain and had a large impact on estimated values. In summary, estimating neurite density generally requires accounting for different diffusion and/or T2 properties between axons and dendrites. Constrained "index" parameters could be valid within limited domains that should be delineated by future studies.