TY - JOUR

T1 - Searching for the neurite density with diffusion MRI: Challenges for biophysical modeling

AU - Lampinen, Björn

AU - Szczepankiewicz, Filip

AU - Novén, Mikael

AU - van Westen, Danielle

AU - Hansson, Oskar

AU - Englund, Elisabet

AU - Mårtensson, Johan

AU - Westin, Carl-Fredrik

AU - Nilsson, Markus

N1 - Publisher Copyright: © 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Anisotropy

KW - Axons

KW - Dendrites

KW - Diffusion MRI

KW - Myelin

KW - Neurites

U2 - 10.1002/hbm.24542

DO - 10.1002/hbm.24542

M3 - Journal article

C2 - 30802367

AN - SCOPUS:85062351656

VL - 40

SP - 2529

EP - 2545

JO - Human Brain Mapping

JF - Human Brain Mapping

SN - 1065-9471

IS - 8

ER -