White matter and nigral alterations in multiple system atrophy-parkinsonian type

Ogawa, Takashi; Hatano, Taku; Kamagata, Koji; Andica, Christina; Takeshige‐Amano, Haruka; Uchida, Wataru; Kamiyama, Daiki; Shimo, Yasushi; Oyama, Genko; Umemura, Atsushi; Iwamuro, Hirokazu; Ito, Masanobu; Hori, Masaaki; Aoki, Shigeki

doi:10.1038/s41531-021-00236-0

Cited by 15 publications

(14 citation statements)

References 73 publications

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“…In neuroimaging, multicompartment dMRI-based approaches were found to offer more specific metrics and to be more sensitive to pathological tissue alterations than singlecompartment DTI [18,42]. Similar assumptions are reasonable for musculoskeletal radiology.…”

Section: Discussionmentioning

confidence: 84%

Application of diffusion microstructure imaging in musculoskeletal radiology — translation from head to shoulders

et al. 2022

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Objectives Quantitative MRI techniques, such as diffusion microstructure imaging (DMI), are increasingly applied for advanced tissue characterization. We determined its value in rotator cuff (RC) muscle imaging by studying the association of DMI parameters to isometric strength and fat fraction (FF). Methods Healthy individuals prospectively underwent 3T-MRI of the shoulder using DMI and chemical shift encoding-based water-fat imaging. RC muscles were segmented and quantitative MRI metrics (V-ISO, free fluid; V-intra, compartment inside of muscle fibers; V-extra, compartment outside of muscle fibers, and FF) were extracted. Isometric shoulder strength was quantified using specific clinical tests. Sex-related differences were assessed with Student’s t. Association of DMI-metrics, FF, and strength was tested. A factorial two-way ANOVA was performed to compare the main effects of sex and external/internal strength-ratio and their interaction effects on quantitative imaging parameters ratios of infraspinatus/subscapularis. Results Among 22 participants (mean age: 26.7 ± 3.1 years, 50% female, mean BMI: 22.6 ± 1.9 kg/m2), FF of the individual RC muscles did not correlate with strength or DMI parameters (all p > 0.05). Subjects with higher V-intra (r = 0.57 to 0.87, p < 0.01) and lower V-ISO (r = −0.6 to −0.88, p < 0.01) had higher internal and external rotation strength. Moreover, V-intra was higher and V-ISO was lower in all RC muscles in males compared to female subjects (all p < 0.01). There was a sex-independent association of external/internal strength-ratio with the ratio of V-extra of infraspinatus/subscapularis (p = 0.02). Conclusions Quantitative DMI parameters may provide incremental information about muscular function and microstructure in young athletes and may serve as a potential biomarker. Key Points • Diffusion microstructure imaging was successfully applied to non-invasively assess the microstructure of rotator cuff muscles in healthy volunteers. • Sex-related differences in the microstructural composition of the rotator cuff were observed. • Muscular microstructural metrics correlated with rotator cuff strength and may serve as an imaging biomarker of muscular integrity and function.

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Section: Discussionmentioning

confidence: 84%

Application of diffusion microstructure imaging in musculoskeletal radiology — translation from head to shoulders

et al. 2022

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“…This important aspect suggests that pathological involvement of the WM structures of cerebellum-brainstem and SN is associated with worsening in the clinical features of the disease and supports the further study of such MRI parameters as surrogate biomarkers of MSA progression. In fact, both WM abnormalities and nigral alterations are interesting markers that are being studied in MSA by means of different techniques with the main purpose of differential diagnosis ( 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

Combined regional T1w/T2w ratio and voxel-based morphometry in multiple system atrophy: A follow-up study

et al. 2022

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Several MRI techniques have become available to support the early diagnosis of multiple system atrophy (MSA), but few longitudinal studies on both MSA variants have been performed, and there are no established MRI markers of disease progression. We aimed to characterize longitudinal brain changes in 26 patients with MSA (14 MSA-P and 12 MSA-C) over a 1-year follow-up period in terms of local tissue density and T1w/T2w ratio in a-priori regions, namely, bilateral putamen, cerebellar gray matter (GM), white matter (WM), and substantia nigra (SN). A significant GM density decrease was found in cerebellum and left putamen in the entire group (10.7 and 33.1% variation, respectively) and both MSA subtypes (MSA-C: 15.4 and 33.0% variation; MSA-P: 7.7 and 33.2%) and in right putamen in the entire group (19.8% variation) and patients with MSA-C (20.9% variation). A WM density decrease was found in the entire group (9.3% variation) and both subtypes in cerebellum-brainstem (MSA-C: 18.0% variation; MSA-P: 5% variation). The T1w/T2w ratio increase was found in the cerebellar and left putamen GM (6.6 and 24.9% variation), while a significant T1w/T2w ratio decrease was detected in SN in the entire MSA group (31% variation). We found a more progressive atrophy of the cerebellum in MSA-C with a similar progression of putaminal atrophy in the two variants. T1w/T2w ratio can be further studied as a potential marker of disease progression, possibly reflecting decreased neuronal density or iron accumulation.

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“…Orientation dispersion (OD) Measure of relative orientations of neurites in tissue (Zhang et al, 2012) High values represent neurites that propagate in many different directions relative to one another; low values represent neurites that propagate in the same direction (Zhang et al, 2012) Isotropic volume fraction (ISOVF) Measures volume fraction of "free water, " or water with unrestricted diffusivity, in tissue (Zhang et al, 2012) High values represent low cell density and/or high volumes of cerebrospinal fluid (CSF) (Zhang et al, 2012) and are associated with neurodegeneration (Ogawa et al, 2021); low values represent high cell or neurite density Intracellular volume fraction (ICVF) Measures volume of space occupied by neurites (Zhang et al, 2012) High values represent areas with highly dense neurites; low values represent areas with low neurite density (Zhang et al, 2012) knowing how genetic background and amyloid pathology together influence neural microanatomy is necessary to determine if brain microanatomy is a strong, heritable source of brain reserve against AD.…”

Section: Neurite Orientation Dispersion and Density Imaging (Noddi)mentioning

confidence: 99%

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

Murdy

Dunn

Singh

et al. 2023

Front. Behav. Neurosci.

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In human Alzheimer’s disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI). To investigate variation of dMRI metrics in pre-disease-onset, genetically diverse AD mouse models, we utilized a population of genetically distinct AD mice produced by crossing the 5XFAD transgenic mouse model of AD to 3 inbred strains (C57BL/6J, DBA/2J, FVB/NJ) and two wild-derived strains (CAST/EiJ, WSB/EiJ). At 3 months of age, these mice underwent diffusion magnetic resonance imaging (dMRI) to probe neural microanatomy in 83 regions of interest (ROIs). At 5 months of age, these mice underwent contextual fear conditioning (CFC). Strain had a significant effect on dMRI measures in most ROIs tested, while far fewer effects of sex, sex*strain interactions, or strain*sex*5XFAD genotype interactions were observed. A main effect of 5XFAD genotype was observed in only 1 ROI, suggesting that the 5XFAD transgene does not strongly disrupt neural development or microstructure of mice in early adulthood. Strain also explained the most variance in mouse baseline motor activity and long-term fear memory. Additionally, significant effects of sex and strain*sex interaction were observed on baseline motor activity, and significant strain*sex and sex*5XFAD genotype interactions were observed on long-term memory. We are the first to study the genetic influences of brain microanatomy in genetically diverse AD mice. Thus, we demonstrated that strain is the primary factor influencing brain microstructure in young adult AD mice and that neural development and early adult microstructure are not strongly altered by the 5XFAD transgene. We also demonstrated that strain, sex, and 5XFAD genotype interact to influence memory in genetically diverse adult mice. Our results support the usefulness of the 5XFAD mouse model and convey strong relationships between natural genetic variation, brain microstructure, and memory.

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White matter and nigral alterations in multiple system atrophy-parkinsonian type

Cited by 15 publications

References 73 publications

Application of diffusion microstructure imaging in musculoskeletal radiology — translation from head to shoulders

Application of diffusion microstructure imaging in musculoskeletal radiology — translation from head to shoulders

Combined regional T1w/T2w ratio and voxel-based morphometry in multiple system atrophy: A follow-up study

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

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