High B-value diffusion tensor imaging for early detection of hippocampal microstructural alteration in a mouse model of multiple sclerosis

Abstract

Several studies have highlighted the value of diffusion tensor imaging (DTI) with strong diffusion weighting to reveal white matter microstructural lesions, but data in gray matter (GM) remains scarce. Herein, the effects of b-values combined with different numbers of diffusion-encoding directions (NDIRs) on DTI metrics to capture the normal hippocampal microstructure and its early alterations were investigated in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis [EAE]). Two initial DTI datasets (B2700-43Dir acquired with b = 2700 s.mm−2 and NDIR = 43; B1000-22Dir acquired with b = 1000 s.mm−2 and NDIR = 22) were collected from 18 normal and 18 EAE mice at 4.7 T. Three additional datasets (B2700-22Dir, B2700-12Dir and B1000-12Dir) were extracted from the initial datasets. In healthy mice, we found a significant influence of b-values and NDIR on all DTI metrics. Confronting unsupervised hippocampal layers classification to the true anatomical classification highlighted the remarkable discrimination of the molecular layer with B2700-43Dir compared with the other datasets. Only DTI from the B2700 datasets captured the dendritic loss occurring in the molecular layer of EAE mice. Our findings stress the needs for both high b-values and sufficient NDIR to achieve a GM DTI with more biologically meaningful correlations, though DTI-metrics should be interpreted with caution in these settings.

Concussions in young adult athletes: No effect on cerebral white matter

“…Longitudinal diffusivity (λ1), or axial diffusivity (AD) was also included in this analysis and can be conceptualized as the degree of diffusion parallel to the underlying fiber tract (Winklewski et al, 2018). It is important to note that prior to fitting the tensor model, data volumes with b up to 1000 were extracted, as the tensor model tends to fall apart with higher diffusion weightings (Crombe et al, 2022).…”

Magnetic resonance imaging approaches for studying mouse models of multiple sclerosis: A mini review

“…Demyelination of the WM is another common feature of EAE. Changes in WM pathology have been detected using a variety of MRI techniques, including magnetization transfer imaging (MTI) (Aharoni et al, 2013; Rausch et al, 2009), susceptibility‐weighted imaging (SWI) (Nathoo et al, 2013), diffusion‐weighted imaging (DWI), and diffusion tensor imaging (DTI) (Alomair et al, 2021; Crombé et al, 2022; Wang et al, 2013). Lesions are observed at the GM/WM boundary, in vital GM structures such as the motor cortex, somatosensory area, and rostral hippocampal regions, in the ventral WM of the spinal cord, in the WM anterior cingulate and external capsule, as well as in the cerebellum.…”

“…For immunohistology analysis, the sections were stained for GFAP and CD11b to visualize astrocytes and macrophage/microglia, respectively (Barazany et al, 2014). A recent study reported then that DTI with a high b-value was able to reveal the microstructural alterations identified by histopathological analysis of dendrites (SMI-32), microglia (Iba1), astrocytes (GFAP), and myelin (MBP), in the molecular layer of the hippocampus of MOG-induced EAE mice (Crombé et al, 2018(Crombé et al, , 2022. In this study, the mean diffusivity (MD) was found to be the most sensitive DTI metric to the early decreases in dendritic length and number of intersections occurring in the hippocampal molecular layer of EAE mice (Crombé et al, 2022).…”

“…A recent study reported then that DTI with a high b-value was able to reveal the microstructural alterations identified by histopathological analysis of dendrites (SMI-32), microglia (Iba1), astrocytes (GFAP), and myelin (MBP), in the molecular layer of the hippocampus of MOG-induced EAE mice (Crombé et al, 2018(Crombé et al, , 2022. In this study, the mean diffusivity (MD) was found to be the most sensitive DTI metric to the early decreases in dendritic length and number of intersections occurring in the hippocampal molecular layer of EAE mice (Crombé et al, 2022). AD and RD were also able to reveal these microstructural alterations, while FA and diffusion Kurtosis imaging (DKI) metrics were unable to detect these changes.…”