Towards higher sensitivity and stability of axon diameter estimation with diffusion-weighted MRI

Sepehrband, Farshid, Alexander, Daniel C., Kurniawan, Nyoman D., Reutens, David C. and Yang, Zhengyi (2016) Towards higher sensitivity and stability of axon diameter estimation with diffusion-weighted MRI. NMR in Biomedicine, 29 3: 293-308. doi:10.1002/nbm.3462


Author Sepehrband, Farshid
Alexander, Daniel C.
Kurniawan, Nyoman D.
Reutens, David C.
Yang, Zhengyi
Title Towards higher sensitivity and stability of axon diameter estimation with diffusion-weighted MRI
Journal name NMR in Biomedicine   Check publisher's open access policy
ISSN 1099-1492
0952-3480
Publication date 2016-03-01
Sub-type Article (original research)
DOI 10.1002/nbm.3462
Open Access Status Not yet assessed
Volume 29
Issue 3
Start page 293
End page 308
Total pages 16
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley and Sons
Language eng
Subject 1313 Molecular Medicine
2741 Radiology Nuclear Medicine and imaging
1607 Spectroscopy
Abstract Diffusion-weighted MRI is an important tool for in vivo and non-invasive axon morphometry. The ActiveAx technique utilises an optimised acquisition protocol to infer orientationally invariant indices of axon diameter and density by fitting a model of white matter to the acquired data. In this study, we investigated the factors that influence the sensitivity to small-diameter axons, namely the gradient strength of the acquisition protocol and the model fitting routine. Diffusion-weighted ex. vivo images of the mouse brain were acquired using 16.4-T MRI with high (G of 300 mT/m) and ultra-high (G of 1350 mT/m) gradient strength acquisitions. The estimated axon diameter indices of the mid-sagittal corpus callosum were validated using electron microscopy. In addition, a dictionary-based fitting routine was employed and evaluated. Axon diameter indices were closer to electron microscopy measures when higher gradient strengths were employed. Despite the improvement, estimated axon diameter indices (a lower bound of~1.8μm) remained higher than the measurements obtained using electron microscopy (~1.2μm). We further observed that limitations of pulsed gradient spin echo (PGSE) acquisition sequences and axonal dispersion could also influence the sensitivity with which axon diameter indices could be estimated. Our results highlight the influence of acquisition protocol, tissue model and model fitting, in addition to gradient strength, on advanced microstructural diffusion-weighted imaging techniques.
Formatted abstract
Diffusion-weighted MRI is an important tool for in vivo and non-invasive axon morphometry. The ActiveAx technique utilises an optimised acquisition protocol to infer orientationally invariant indices of axon diameter and density by fitting a model of white matter to the acquired data. In this study, we investigated the factors that influence the sensitivity to small-diameter axons, namely the gradient strength of the acquisition protocol and the model fitting routine. Diffusion-weighted ex. vivo images of the mouse brain were acquired using 16.4-T MRI with high (Gmax of 300 mT/m) and ultra-high (Gmax of 1350 mT/m) gradient strength acquisitions. The estimated axon diameter indices of the mid-sagittal corpus callosum were validated using electron microscopy. In addition, a dictionary-based fitting routine was employed and evaluated. Axon diameter indices were closer to electron microscopy measures when higher gradient strengths were employed. Despite the improvement, estimated axon diameter indices (a lower bound of ~ 1.8 μm) remained higher than the measurements obtained using electron microscopy (~1.2 μm). We further observed that limitations of pulsed gradient spin echo (PGSE) acquisition sequences and axonal dispersion could also influence the sensitivity with which axon diameter indices could be estimated. Our results highlight the influence of acquisition protocol, tissue model and model fitting, in addition to gradient strength, on advanced microstructural diffusion-weighted imaging techniques.
Keyword ActiveAx
Axon diameter index
Diffusion-weighted MRI
Electron microscopy
Histological validation
Mouse corpus callosum
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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