On the Viability of Diffusion MRI-Based Microstructural Biomarkers in Ischemic Stroke

Abstract

Recent tract-based analyses provided evidence for the exploitability of 3D-SHORE microstructural descriptors derived from diffusion MRI (dMRI) in revealing white matter (WM) plasticity. In this work, we focused on the main open issues left: (1) the comparative analysis with respect to classical tensor-derived indices, i.e., Fractional Anisotropy (FA) and Mean Diffusivity (MD); and (2) the ability to detect plasticity processes in gray matter (GM). Although signal modeling in GM is still largely unexplored, we investigated their sensibility to stroke-induced microstructural modifications occurring in the contralateral hemisphere. A more complete picture could provide hints for investigating the interplay of GM and WM modulations. Ten stroke patients and ten age/gender-matched healthy controls were enrolled in the study and underwent diffusion spectrum imaging (DSI). Acquisitions at three and two time points (tp) were performed on patients and controls, respectively. For all subjects and acquisitions, FA and MD were computed along with 3D-SHORE-based indices [Generalized Fractional Anisotropy (GFA), Propagator Anisotropy (PA), Return To the Axis Probability (RTAP), Return To the Plane Probability (RTPP), and Mean Square Displacement (MSD)]. Tract-based analysis involving the cortical, subcortical and transcallosal motor networks and region-based analysis in GM were successively performed, focusing on the contralateral hemisphere to the stroke. Reproducibility of all the indices on both WM and GM was quantitatively proved on controls. For tract-based, longitudinal group analyses revealed the highest significant differences across the subcortical and transcallosal networks for all the indices. The optimal regression model for predicting the clinical motor outcome at tp3 included GFA, PA, RTPP, and MSD in the subcortical network in combination with the main clinical information at baseline. Region-based analysis in the contralateral GM highlighted the ability of anisotropy indices in discriminating between groups mainly at tp1, while diffusivity indices appeared to be altered at tp2. 3D-SHORE indices proved to be suitable in probing plasticity in both WM and GM, further confirming their viability as a novel family of biomarkers in ischemic stroke in WM and revealing their potential exploitability in GM. Their combination with tensor-derived indices can provide more detailed insights of the different tissue modulations related to stroke pathology.

Microstructure Diffusion Scalar Measures from Reduced MRI Acquisitions

“…In particular, RTOP has also demonstrated to be a better indicator for cellularity and diffusion restrictions than the DTI-related mean diffusivity (MD) (Avram et al, 2016) and, together with MSD, a proper measure for the assessment of myelination (Alimi et al, 2018). These results were later confirmed by Boscolo Galazzo et al (2018), where the authors reinforced the hypothesis on RTOP to have greater specificity to reflect cellularity and restricted diffusion.…”

“…Although the use of these measures is not generalized among the clinical community, there is a growing interest on the exploration of their potential clinical applicability. To date, the relevance of scalar descriptors of the brain microstructure has been proved on both ex vivo (Daianu et al, 2015;Ozarslan et al, 2013;Fick et al, 2016a) and in vivo studies of healthy and diseased subjects (Brusini et al, 2015;Hosseinbor et al, 2012;Avram et al, 2016;Brusini et al, 2016;Boscolo Galazzo et al, 2018;Zucchelli et al, 2016). In particular, RTOP has also demonstrated to be a better indicator for cellularity and diffusion restrictions than the DTI-related mean diffusivity (MD) (Avram et al, 2016) and, together with MSD, a proper measure for the assessment of myelination (Alimi et al, 2018).…”

Characterization of the Basal Ganglia Using Diffusion Tensor Imaging in Children with Self‐Injurious Behavior and Tuberous Sclerosis Complex

“…Within the gray matter, the principally cellular microstructure typically has predominant isotropic diffusion characteristics that are best evaluated by apparent diffusion coefficient (ADC) maps . However, multiple studies have shown that FA values, markers of anisotropic diffusion, may also alter the microstructural anatomy if affected by a diffuse process . For example, in patients with a cortical stroke, the FA values may increase within the cortical gray matter, likely secondary to a combination of cytotoxic and vasogenic edema impacting the diffusion of water molecules within the extracellular space .…”

Micro-structure diffusion scalar measures from reduced MRI acquisitions

“…Although the use of these measures is not generalized among the clinical community, there is a growing interest in the exploration of their potential clinical applicability. To date, the relevance of scalar descriptors of the brain micro-structure has been proved on both ex vivo [12,25,26] and in vivo studies of healthy and diseased subjects [22,23,[27][28][29][30]. In particular, RTOP has also demonstrated to be a better indicator for cellularity and diffusion restrictions than the DTI-related mean diffusivity (MD) [22] and, together with MSD, a proper measure for the assessment of myelination [31].…”

“…In particular, RTOP has also demonstrated to be a better indicator for cellularity and diffusion restrictions than the DTI-related mean diffusivity (MD) [22] and, together with MSD, a proper measure for the assessment of myelination [31]. These results were later confirmed by [29], where the authors reinforced the hypothesis on RTOP to have greater sensitivity to reflect cellularity and restricted diffusion.…”