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Journal of Neurology Mar 2023Enzyme replacement therapy has drastically changed prospects of patients with Pompe disease, a progressive metabolic myopathy. As classic infantile patients survive due...
Enzyme replacement therapy has drastically changed prospects of patients with Pompe disease, a progressive metabolic myopathy. As classic infantile patients survive due to treatment, they exhibit progressive white matter abnormalities, while brain involvement in late-onset patients is not fully elucidated. To study the underlying microstructure of white matter, we acquired structural (T1, T2, FLAIR) and diffusion tensor imaging (DTI) of the brain in 12 classic infantile patients (age 5-20 years) and 18 late-onset Pompe patients (age 11-56 years). Structural images were scored according to a rating scale for classic infantile patients. Fractional anisotropy (FA) and mean diffusivity (MD) from classic infantile patients were compared to a reference population, using a Wilcoxon signed-rank, one sample test. Effect sizes (Hedges' G) were used to compare DTI metrics across different tracts. For late-onset patients, results were compared to (reported) tractography data on normal aging. In classic infantile patients, we found a significant lower FA and higher MD (p < 0.01) compared to the reference population. Large-association fibers were most severely affected. Classic infantile patients with advanced white matter abnormalities on structural MRI showed the largest deviations from the reference population. FA and MD were similar for younger and older late-onset patients in large WM-association fibers. We conclude that, while no deviations from typical neurodevelopment were found in late-onset patients, classic infantile Pompe patients showed quantifiable, substantially altered white matter microstructure, which corresponded with disease stage on structural MRI. DTI holds promise to monitor therapy response in future therapies targeting the brain.
Topics: Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Diffusion Tensor Imaging; Glycogen Storage Disease Type II; Brain; White Matter; Diffusion Magnetic Resonance Imaging; Anisotropy
PubMed: 36480052
DOI: 10.1007/s00415-022-11506-z -
Annals of Clinical and Translational... Jul 2022The underlying neuropathological process of amyotrophic lateral sclerosis (ALS) can be classified in a four-stage sequential pTDP-43 cerebral propagation scheme. Using...
BACKGROUND
The underlying neuropathological process of amyotrophic lateral sclerosis (ALS) can be classified in a four-stage sequential pTDP-43 cerebral propagation scheme. Using diffusion tensor imaging (DTI), in vivo imaging of these stages has already been shown to be feasible for the specific corticoefferent tract systems. Because both cognitive and oculomotor dysfunctions are associated with microstructural changes at the brain level in ALS, a cognitive and an oculomotor staging classification were developed, respectively. The association of these different in vivo staging schemes has not been attempted to date.
METHODS
A total of 245 patients with ALS underwent DTI, video-oculography, and cognitive testing using Edinburgh Cognitive and Behavioral ALS Screen (ECAS). A set of tract-related diffusion metrics, cognitive, and oculomotor parameters was selected for further analysis. Hierarchical and k-means clustering algorithms were used to obtain an optimal cluster solution.
RESULTS
According to cluster analysis, differentiation of patients with ALS into four clusters resulted: Cluster A showed the highest fractional anisotropy (FA) values and thereby the best performances in executive oculomotor tasks and cognitive tests, whereas cluster D showed the lowest FA values, the lowest ECAS scores, and the worst executive oculomotor performance across all clusters. Clusters B and C showed intermediate results regarding parameter values.
DISCUSSION
In a multimodal dataset of technical assessments of brain structure and function in ALS, an artificial intelligence-based cluster analysis showed high congruence of DTI, executive oculomotor function, and neuropsychological performance for mapping in vivo correlates of neuropathological spreading.
Topics: Amyotrophic Lateral Sclerosis; Anisotropy; Artificial Intelligence; Brain; Diffusion Tensor Imaging; Humans
PubMed: 35684940
DOI: 10.1002/acn3.51601 -
NeuroImage. Clinical 2022Widespread white matter abnormalities are a frequent finding in chronic schizophrenia patients. More inconsistent results have been provided by the sparser literature on...
BACKGROUND
Widespread white matter abnormalities are a frequent finding in chronic schizophrenia patients. More inconsistent results have been provided by the sparser literature on at-risk states for psychosis, i.e., emerging subclinical symptoms. However, considering risk as a homogenous construct, an approach of earlier studies, may impede our understanding of neuro-progression into psychosis.
METHODS
An analysis was conducted of 3-Tesla MRI diffusion and symptom data from 112 individuals (mean age, 21.97 ± 4.19) within two at-risk paradigm subtypes, only basic symptoms (n = 43) and ultra-high risk (n = 37), and controls (n = 32). Between-group comparisons (involving three study groups and further split based on the subsequent transition to schizophrenia) of four diffusion-tensor-imaging-derived scalars were performed using voxelwise tract-based spatial statistics, followed by correlational analyses with Structured Interview for Prodromal Syndromes responses.
RESULTS
Relative to controls, fractional anisotropy was lower in the splenium of the corpus callosum of ultra-high-risk individuals, but only before stringent multiple-testing correction, and negatively correlated with General Symptom severity among at-risk individuals. At-risk participants who transitioned to schizophrenia within 3 years, compared to those that did not transition, had more severe WM differences in fractional anisotropy and radial diffusivity (particularly in the corpus callosum, anterior corona radiata, and motor/sensory tracts), which were even more extensive compared to healthy controls.
CONCLUSIONS
These findings align with the subclinical symptom presentation and more extensive disruptions in converters, suggestive of severity-related demyelination or axonal pathology. Fine-grained but detectable differences among ultra-high-risk subjects (i.e., with brief limited intermittent and/or attenuated psychotic symptoms) point to the splenium as a discrete site of emerging psychopathology, while basic symptoms alone were not associated with altered fractional anisotropy.
Topics: Adolescent; Adult; Anisotropy; Diffusion Tensor Imaging; Humans; Prodromal Symptoms; Psychotic Disorders; Schizophrenia; White Matter; Young Adult
PubMed: 35679786
DOI: 10.1016/j.nicl.2022.103067 -
Investigative Radiology Dec 2021The objectives of this exploratory study were to investigate the feasibility of multidimensional diffusion magnetic resonance imaging (MddMRI) in assessing diffusion...
OBJECTIVES
The objectives of this exploratory study were to investigate the feasibility of multidimensional diffusion magnetic resonance imaging (MddMRI) in assessing diffusion heterogeneity at both a macroscopic and microscopic level in prostate cancer (PCa).
MATERIALS AND METHODS
Informed consent was obtained from 46 subjects who underwent 3.0-T prostate multiparametric MRI, complemented with a prototype spin echo-based MddMRI sequence in this institutional review board-approved study. Prostate cancer tumors and comparative normal tissue from each patient were contoured on both apparent diffusion coefficient and MddMRI-derived mean diffusivity (MD) maps (from which microscopic diffusion heterogeneity [MKi] and microscopic diffusion anisotropy were derived) using 3D Slicer. The discriminative ability of MddMRI-derived parameters to differentiate PCa from normal tissue was determined using the Friedman test. To determine if tumor diffusion heterogeneity is similar on macroscopic and microscopic scales, the linear association between SD of MD and mean MKi was estimated using robust regression (bisquare weighting). Hypothesis testing was 2 tailed; P values less than 0.05 were considered statistically significant.
RESULTS
All MddMRI-derived parameters could distinguish tumor from normal tissue in the fixed-effects analysis (P < 0.0001). Tumor MKi was higher (P < 0.05) compared with normal tissue (median, 0.40; interquartile range, 0.29-0.52 vs 0.20-0.18; 0.25), as was tumor microscopic diffusion anisotropy (0.55; 0.36-0.81 vs 0.20-0.15; 0.28). The MKi could not be predicted (no significant association) by SD of MD. There was a significant correlation between tumor volume and SD of MD (R2 = 0.50, slope = 0.008 μm2/ms per millimeter, P < 0.001) but not between tumor volume and MKi.
CONCLUSIONS
This explorative study demonstrates that MddMRI provides novel information on MKi and microscopic anisotropy, which differ from measures at the macroscopic level. MddMRI has the potential to characterize tumor tissue heterogeneity at different spatial scales.
Topics: Anisotropy; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; Male; Pilot Projects; Prostatic Neoplasms
PubMed: 34049334
DOI: 10.1097/RLI.0000000000000796 -
PloS One 2021Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and...
BACKGROUND AND PURPOSE
Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and injury models. Oscillating gradient spin echo (OGSE) dMRI, implemented by varying the oscillating gradient frequency, and microscopic anisotropy (μA) dMRI, implemented via tensor valued diffusion encoding, may provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The aims of this study were to characterize the test-retest reproducibility of in vivo OGSE and μA dMRI metrics in the mouse brain at 9.4 Tesla and provide estimates of required sample sizes for future investigations.
METHODS
Twelve adult C57Bl/6 mice were scanned twice (5 days apart). Each imaging session consisted of multifrequency OGSE and μA dMRI protocols. Metrics investigated included μA, linear diffusion kurtosis, isotropic diffusion kurtosis, and the diffusion dispersion rate (Λ), which explores the power-law frequency dependence of mean diffusivity. The dMRI metric maps were analyzed with mean region-of-interest (ROI) and whole brain voxel-wise analysis. Bland-Altman plots and coefficients of variation (CV) were used to assess the reproducibility of OGSE and μA metrics. Furthermore, we estimated sample sizes required to detect a variety of effect sizes.
RESULTS
Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for most metrics (CVs < 15%). Voxel-wise CV maps revealed high reproducibility for μA (CVs ~ 10%), but low reproducibility for OGSE metrics (CVs ~ 50%).
CONCLUSION
Most of the μA dMRI metrics are reproducible in both ROI-based and voxel-wise analysis, while the OGSE dMRI metrics are only reproducible in ROI-based analysis. Given feasible sample sizes (10-15), μA metrics and OGSE metrics may provide sensitivity to subtle microstructural changes (4-8%) and moderate changes (> 6%), respectively.
Topics: Animals; Anisotropy; Brain; Diffusion Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Reproducibility of Results
PubMed: 34739479
DOI: 10.1371/journal.pone.0255711 -
Neuropsychopharmacology : Official... Mar 2022Corpus callosum (CC) abnormalities have been observed in several psychiatric disorders. Maltreatment has also been associated with marked differences in CC anatomy and...
Corpus callosum (CC) abnormalities have been observed in several psychiatric disorders. Maltreatment has also been associated with marked differences in CC anatomy and microstructure, though rarely controlled for in psychiatric neuroimaging studies. The aim of this study was to identify type and timing of maltreatment associated with alterations in CC microstructure and to ascertain if they differ by sex. T1 and diffusion-weighted MRIs were obtained from 345 (135 M/210 F) healthy 18-25-year-olds. The Maltreatment and Abuse Chronology of Exposure scale provided retrospective data on exposure to ten types of maltreatment across each year of childhood. AI predictive analytics were used to identify the most significant type and time risk factors. The most striking maltreatment-associated alterations in males were in axial diffusivity and were most specifically associated with exposure to emotional abuse or neglect during segment-specific sensitive periods. In contrast, maltreatment was associated with marked alteration in radial diffusivity and fractional anisotropy in females and was most specifically associated with early physical neglect during one common sensitive period involving all segments except the splenium. Overall sex differences, controlling for maltreatment, brain size, and sociodemographic factors were limited to the genu with greater fractional anisotropy in males and radial diffusivity in females. These findings suggest that maltreatment may target myelinization in females and axonal development in males and that these sex differences need to be taken into account in studies seeking to delineate the contribution of CC abnormalities and interhemispheric communication to psychiatric disorders.
Topics: Anisotropy; Child; Corpus Callosum; Diffusion Tensor Imaging; Female; Humans; Male; Neuroimaging; Retrospective Studies
PubMed: 35022536
DOI: 10.1038/s41386-021-01260-7 -
Magnetic Resonance in Medicine Dec 2021Diffusion-weighted imaging allows investigators to identify structural, microstructural, and connectivity-based differences between subjects, but variability due to...
PURPOSE
Diffusion-weighted imaging allows investigators to identify structural, microstructural, and connectivity-based differences between subjects, but variability due to session and scanner biases is a challenge.
METHODS
To investigate DWI variability, we present MASiVar, a multisite data set consisting of 319 diffusion scans acquired at 3 T from b = 1000 to 3000 s/mm across 14 healthy adults, 83 healthy children (5 to 8 years), three sites, and four scanners as a publicly available, preprocessed, and de-identified data set. With the adult data, we demonstrate the capacity of MASiVar to simultaneously quantify the intrasession, intersession, interscanner, and intersubject variability of four common DWI processing approaches: (1) a tensor signal representation, (2) a multi-compartment neurite orientation dispersion and density model, (3) white-matter bundle segmentation, and (4) structural connectomics. Respectively, we evaluate region-wise fractional anisotropy, mean diffusivity, and principal eigenvector; region-wise CSF volume fraction, intracellular volume fraction, and orientation dispersion index; bundle-wise shape, volume, fractional anisotropy, and length; and whole connectome correlation and maximized modularity, global efficiency, and characteristic path length.
RESULTS
We plot the variability in these measures at each level and find that it consistently increases with intrasession to intersession to interscanner to intersubject effects across all processing approaches and that sometimes interscanner variability can approach intersubject variability.
CONCLUSIONS
This study demonstrates the potential of MASiVar to more globally investigate DWI variability across multiple levels and processing approaches simultaneously and suggests harmonization between scanners for multisite analyses should be considered before inference of group differences on subjects.
Topics: Adult; Anisotropy; Brain; Child; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; Neurites; White Matter
PubMed: 34270123
DOI: 10.1002/mrm.28926 -
Journal of Integrative Neuroscience Jul 2022This study aims to explore the features of gait disorders with cerebral small vessel disease (CSVD), and results from magnetic resonance imaging (MRI) with diffusion...
BACKGROUND
This study aims to explore the features of gait disorders with cerebral small vessel disease (CSVD), and results from magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) were analyzed.
METHODS
The 139 patients with CSVD were divided into two groups by the Tinetti scale scores: the gait disorder (GD) group with a score <24 (63 patients) and the normal gait (GN) group with a score ≥24 (76 patients). A series of scales and 3.0T MRI with DTI were used to analyze the correlation between the abnormal gaits and imaging findings.
RESULTS
The differences in the Barthel Index, Unified Parkinson's Disease Rating Scale part III, and Montreal Cognitive Assessment (MoCA) scores between the two groups were significant ( < 0.05), and there were significant correlations between MoCA and total gait scores ( 0.201, = 0.002). The GD group had a more degraded gait score, widened gait base, and degraded gait length than the GN group ( < 0.05). There were significant differences between the two groups ( < 0.05) in white matter (WM) hyperintensities (WMH) of the Fazekas scale grade 2-3 and lacunes. The GD group had a greater total MRI burden than the GN group ( < 0.05). In DTI parameters, the GD group had lower fractional anisotropy (FA) and higher mean diffusion (MD) values in WM tracts in many areas around the ventricles (family-wise error corrected, < 0.05). Significant correlations were observed between FA and the total gait score ( 0.467, < 0.01), and also between MD and total gait score ( = -0.422, < 0.01).
CONCLUSIONS
Patients with CSVD with gait disorders had more WMH of Fazekas scale grade 2-3, lacunes, and total MRI burden than the GN patients, and those with gait disorders may suffer from demyelination of nerve fibers and damage to the fibers' microstructures.
Topics: Aged; Anisotropy; Cerebral Small Vessel Diseases; Diffusion Tensor Imaging; Gait; Humans; Magnetic Resonance Imaging
PubMed: 36137968
DOI: 10.31083/j.jin2105129 -
International Journal of Geriatric... Sep 2021Agitation and aggression are common in dementia and pre-dementia. The dementia risk syndrome mild behavioral impairment (MBI) includes these symptoms in the impulse...
OBJECTIVES
Agitation and aggression are common in dementia and pre-dementia. The dementia risk syndrome mild behavioral impairment (MBI) includes these symptoms in the impulse dyscontrol domain. However, the neural circuitry associated with impulse dyscontrol in neurodegenerative disease is not well understood. The objective of this work was to investigate if regional micro- and macro-structural brain properties were associated with impulse dyscontrol symptoms in older adults with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD).
METHODS
Clinical, neuropsychiatric, and T1-weighted and diffusion-tensor magnetic resonance imaging (DTI) data from 80 individuals with and 123 individuals without impulse dyscontrol were obtained from the AD Neuroimaging Initiative. Linear mixed effect models were used to assess if impulse dyscontrol was related to regional DTI and volumetric parameters.
RESULTS
Impulse dyscontrol was present in 17% of participants with NC, 43% with MCI, and 66% with AD. Impulse dyscontrol was associated with: (1) lower fractional anisotropy (FA), and greater mean, axial, and radial diffusivity in the fornix; (2) lesser FA and greater radial diffusivity in the superior fronto-occipital fasciculus; (3) greater axial diffusivity in the cingulum; (4) greater axial and radial diffusivity in the uncinate fasciculus; (5) gray matter atrophy, specifically, lower cortical thickness in the parahippocampal gyrus.
CONCLUSION
Our findings provide evidence that well-established atrophy patterns of AD are prominent in the presence of impulse dyscontrol, even when disease status is controlled for, and possibly in advance of dementia. Our findings support the growing evidence for impulse dyscontrol symptoms as an early manifestation of AD.
Topics: Aged; Alzheimer Disease; Anisotropy; Brain; Cognitive Dysfunction; Diffusion Tensor Imaging; Humans; Neurodegenerative Diseases; Neuropsychological Tests; White Matter
PubMed: 33778998
DOI: 10.1002/gps.5540 -
Medical Image Analysis Dec 2021Elastography has become widely used clinically for characterising changes in soft tissue mechanics that are associated with altered tissue structure and composition....
Elastography has become widely used clinically for characterising changes in soft tissue mechanics that are associated with altered tissue structure and composition. However, some soft tissues, such as muscle, are not isotropic as is assumed in clinical elastography implementations. This limits the ability of these methods to capture changes in anisotropic tissues associated with disease. The objective of this study was to develop and validate a novel elastography reconstruction technique suitable for estimating the linear viscoelastic mechanical properties of transversely isotropic soft tissues. We derived a divergence-free formulation of the governing equations for acoustic wave propagation through a linearly transversely isotropic viscoelastic material, and transformed this into a weak form. This was then implemented into a finite element framework, enabling the analysis of wave input data and tissue structural fibre orientations, in this case based on diffusion tensor imaging. To validate the material constants obtained with this method, numerous in silico phantom experiments were run which encompassed a range of variations in wave input directions, material properties, fibre structure and noise. The method was also tested on ex vivo muscle and in vivo human volunteer calf muscles, and compared with a previous curl-based inversion method. The new method robustly extracted the transversely isotropic shear moduli (G, G, G) from the in silico phantom tests with minimal bias, including in the presence of experimentally realistic levels of noise in either fibre orientation or wave data. This new method performed better than the previous method in the presence of noise. Anisotropy estimates from the ex vivo muscle phantom agreed well with rheological tests. In vivo experiments on human calf muscles were able to detect increases in muscle shear moduli with passive muscle stretch. This new reconstruction method can be applied to quantify tissue mechanical properties of anisotropic soft tissues, such as muscle, in health and disease.
Topics: Anisotropy; Diffusion Tensor Imaging; Elasticity; Elasticity Imaging Techniques; Humans; Phantoms, Imaging
PubMed: 34587584
DOI: 10.1016/j.media.2021.102212