Abstract
Recent advances in diffusion magnetic resonance imaging (dMRI) analysis techniques have improved our understanding of fibre‐specific variations in white matter microstructure. Increasingly, studies are adopting multi‐shell dMRI acquisitions to improve the robustness of dMRI‐based inferences. However, the impact of b‐value choice on the estimation of dMRI measures such as apparent fibre density (AFD) derived from spherical deconvolution is not known. Here, we investigate the impact of b‐value sampling scheme on estimates of AFD. First, we performed simulations to assess the correspondence between AFD and simulated intra‐axonal signal fraction across multiple b‐value sampling schemes. We then studied the impact of sampling scheme on the relationship between AFD and age in a developmental population (n = 78) aged 8–18 (mean = 12.4, SD = 2.9 years) using hierarchical clustering and whole brain fixel‐based analyses. Multi‐shell dMRI data were collected at 3.0T using ultra‐strong gradients (300 mT/m), using 6 diffusion‐weighted shells ranging from b = 0 to 6,000 s/mm2. Simulations revealed that the correspondence between estimated AFD and simulated intra‐axonal signal fraction was improved with high b‐value shells due to increased suppression of the extra‐axonal signal. These results were supported by in vivo data, as sensitivity to developmental age‐relationships was improved with increasing b‐value (b = 6,000 s/mm2, median R 2 = .34; b = 4,000 s/mm2, median R 2 = .29; b = 2,400 s/mm2, median R 2 = .21; b = 1,200 s/mm2, median R 2 = .17) in a tract‐specific fashion. Overall, estimates of AFD and age‐related microstructural development were better characterised at high diffusion‐weightings due to improved correspondence with intra‐axonal properties.
Highlights
Diffusion magnetic resonance imaging offers a magnified window into white matter by probing the tissue microstructure properties
Combining fixel-based analysis (FBA) with the very latest in MRI gradient hardware (300 mT/m) (Jones et al, 2018), we explore the impact of sampling scheme on apparent fibre density (AFD) estimates using a rich developmental dataset comprising multi-shell diffusion MRI data with b-values ranging from 0 to 6,000 s/mm2
Separate statistical analyses were performed for each single-shell sampling scheme (b = 1,200; 2,400; 4,000; 6,000 s/mm2) using connectivity-based fixel enhancement (CFE), which provides a permutation-based, family-wise error (FWE) corrected p-value for every individual fixel in the template image (Raffelt et al, 2015)
Summary
Diffusion magnetic resonance imaging (dMRI; Le Bihan & Breton, 1985) offers a magnified window into white matter by probing the tissue microstructure properties. With the advent of multi-slice accelerated imaging (Barth, Breuer, Koopmans, Norris, & Poser, 2016), the acquisition of multiple dMRI shells has become more feasible This has considerably improved data acquisition capabilities for sensitive populations (such as children and clinical populations) which may not withstand long acquisition times (Kunz et al, 2014; Silk et al, 2016; Somerville et al, 2018). Measures derived from constrained spherical deconvolution (CSD; Dell'Acqua & Tournier, 2019) can infer the intra-axonal signal fraction along multiple fibre pathways (Dell'Acqua, Simmons, Williams, & Catani, 2013; Raffelt et al, 2012) One such measure of microstructural organisation, termed apparent fibre density (AFD), can indicate relative differences in the white matter fibre density per unit volume of tissue. We conduct experiments to confirm the theory that AFD is more sensitive and specific to axon density at higher b-values, demonstrated by sensitivity to detecting age-relationships in a developmental population of children and adolescents
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