scholarly journals Diffusion MRI Captures White Matter Microstructure Alterations in PRKN Disease

2021 ◽  
pp. 1-15
Author(s):  
Takahiro Koinuma ◽  
Taku Hatano ◽  
Koji Kamagata ◽  
Christina Andica ◽  
Akio Mori ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Diffusion Mri ◽  
Disease Duration ◽  
Diffusion Tensor ◽  
Neuronal Degeneration ◽  
Mean Diffusivity ◽  
B Value ◽  
Oxidative Stress Marker ◽  
Systemic Oxidative Stress

Background: Although pathological studies usually indicate pure dopaminergic neuronal degeneration in patients with parkin (PRKN) mutations, there is no evidence to date regarding white matter (WM) pathology. A previous diffusion MRI study has revealed WM microstructural alterations caused by systemic oxidative stress in idiopathic Parkinson’s disease (PD), and we found that PRKN patients have systemic oxidative stress in serum biomarker studies. Thus, we hypothesized that PRKN mutations might lead to WM abnormalities. Objective: To investigate whether there are WM microstructural abnormalities in early-onset PD patients with PRKN mutations using diffusion tensor imaging (DTI). Methods: Nine PRKN patients and 19 age- and sex-matched healthy controls were recruited. DTI measures were acquired on a 3T MR scanner using a b value of 1,000 s/mm2 along 32 isotropic diffusion gradients. The DTI measures were compared between groups using tract-based spatial statistics (TBSS) analysis. Correlation analysis was also performed between the DTI parameters and several serum oxidative stress markers obtained in a previously conducted metabolomic analysis. Results: Although the WM volumes were not significantly different, the TBSS analysis revealed a corresponding decrease in fractional anisotropy and an increase in mean diffusivity and radial diffusivity in WM areas, such as the anterior and superior corona radiata and uncinate fasciculus, in PRKN patients compared with controls. Furthermore, 9-hydroxystearate, an oxidative stress marker, and disease duration were positively correlated with several parameters in PRKN patients. Conclusion: This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress.

scholarly journals Perivascular space fluid contributes to diffusion tensor imaging changes in white matter

2018 ◽  
Author(s):  
Farshid Sepehrband ◽  
Ryan P Cabeen ◽  
Jeiran Choupan ◽  
Giuseppe Barisano ◽  
Meng Law ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Mri ◽  
Diffusion Tensor ◽  
Diffusion Imaging ◽  
Mean Diffusivity ◽  
Brain Parenchyma ◽  
Perivascular Space ◽  
List Type

AbstractDiffusion tensor imaging (DTI) has been extensively used to map changes in brain tissue related to neurological disorders. Among the most widespread DTI findings are increased mean diffusivity and decreased fractional anisotropy of white matter tissue in neurodegenerative diseases. Here we utilize multi-shell diffusion imaging to separate diffusion signal of the brain parenchyma from fluid within the white matter. We show that unincorporated anisotropic water in perivascular space (PVS) significantly, and systematically, biases DTI measures, casting new light on the biological validity of many previously reported findings. Despite the challenge this poses for interpreting these past findings, our results suggest that multi-shell diffusion MRI provides a new opportunity for incorporating the PVS contribution, ultimately strengthening the clinical and scientific value of diffusion MRI.HighlightsPerivascular space (PVS) fluid significantly contributes to diffusion tensor imaging metricsIncreased PVS fluid results in increased mean diffusivity and decreased fractional anisotropyPVS contribution to diffusion signal is overlooked and demands further investigation

scholarly journals Diffusion MRI Changes in the Healthy Aging Canine Brain

2020 ◽  
Author(s):  
Erica F. Barry ◽  
John P. Loftus ◽  
Wen-Ming Luh ◽  
Mony J. de Leon ◽  
Sumit N. Niogi ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Healthy Aging ◽  
Parietal Lobe ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Human Aging ◽  
Age Related ◽  
Age Related Changes

AbstractWhite matter dysfunction and degeneration have been a topic of great interest in healthy and pathological aging. While ex vivo studies have investigated age-related changes in canines, little in vivo canine aging research exists. Quantitative diffusion MRI such as diffusion tensor imaging (DTI) has demonstrated aging and neurodegenerative white matter changes in humans. However, this method has not been applied and adapted in vivo to canine populations. This study aimed to test the hypothesis that white matter diffusion changes frequently reported in human aging are also found in aged canines. The study used Tract Based Spatial Statistics (TBSS) and a region of interest (ROI) approach to investigate age related changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). The results show that, compared to younger animals, aged canines have significant decreases in FA in parietal and temporal regions as well as the corpus callosum and fornix. Additionally, AxD decreases were observed in parietal, frontal and midbrain regions. Similarly, an age-related increase in RD was observed in the right parietal lobe while MD decreases were found in the midbrain. These findings suggest that canine samples offer a model for healthy human aging as they exhibit similar white matter diffusion tensor changes with age.

scholarly journals Loss and Reorganisation of Superficial White Matter in Alzheimer's disease: A Diffusion MRI study

2021 ◽  
Author(s):  
Thomas Veale ◽  
Ian B Malone ◽  
Teresa Poole ◽  
Thomas D Parker ◽  
Catherine F Slattery ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Mri ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Young Onset ◽  
Neurite Density

Pathological involvement of cerebral white matter in Alzheimer's disease has been shown using diffusion tensor imaging. Superficial white matter (SWM) changes have been relatively understudied despite their importance in cortico-cortical connections. Measuring SWM degeneration using diffusion tensor imaging is challenging due to its complex structure and proximity to the cortex. To overcome this we investigated diffusion MRI changes in young-onset Alzheimer's disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are due to degeneration (e.g. loss of myelinated fibres) and those due to reorganisation (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer's disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, the grey/white boundary, SWM (1mm below grey/white boundary) and SWM/deeper white matter (2mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants' diffusion metrics along the cortical profile. The SWM of young-onset Alzheimer's disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P<0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P<0.05). Young-onset Alzheimer's disease individuals had lower fractional anisotropy in the SWM of two regions (entorhinal and parahippocampus) (both P<0.05) and higher fractional anisotropy within the postcentral region (P<0.05). Mean diffusivity in SWM was higher in the young-onset Alzheimer's disease group in the parahippocampal region (P<0.05) and lower in three regions (postcentral, precentral and superior temporal) (all P<0.05). In the overlying grey matter, disease-related changes were largely consistent with SWM findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity SWM changes. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer's disease individuals (all P<0.001) but group differences reduced in magnitude and coverage when moving towards the SWM. These results show that microstructural changes occur within SWM and along the cortical profile in individuals with young-onset Alzheimer's disease. Lower neurite density and higher orientation dispersion suggests underlying SWM fibres undergo neurodegeneration and reorganisation, two effects previously indiscernible using standard diffusion tensor metrics in SWM.

scholarly journals Alterations in Diffusion Measures of White Matter Integrity Associated with Healthy Aging

2019 ◽  
Author(s):  
Ciara J Molloy ◽  
Sinead Nugent ◽  
Arun L W Bokde
Keyword(s):  
White Matter ◽  
Healthy Aging ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
B Value ◽  
White Matter Hyperintensity ◽  
Normal Appearing White Matter ◽  
Age Related ◽  
Aging Adults ◽  
The Impact

Abstract This study aimed to characterize age-related white matter changes by evaluating patterns of overlap between the linear association of age with fractional anisotropy (FA) with mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Specifically, we assessed patterns of overlap between diffusion measures of normal appearing white matter by covarying for white matter hyperintensity (WMH) load, as WMHs are thought to increase with age and impact diffusion measures. Seventy-nine healthy adults aged between 18 and 75 years took part in the study. Diffusion tensor imaging (DTI) data were based on 61 directions acquired with a b-value of 2,000. We found five main patterns of overlap: FA alone (15.95%); FA and RD (31.90%); FA and AD (12.99%); FA, RD, and AD (27.93%); and FA, RD, and MD (8.79%). We showed that cognitively healthy aging adults had low WMH load, which subsequently had minimal effect on diffusion measures. We discuss how patterns of overlap may reflect underlying biological changes observed with aging such as loss of myelination, axonal damage, as well as mild microstructural and chronic white matter impairments. This study contributes to understanding the underlying causes of degeneration in specific regions of the brain and highlights the importance of considering the impact of WMHs in aging studies of white matter.

Diffusion Tensor Metric Measurements as a Function of Diffusion Time in the Rat Central Nervous System

2012 ◽  
Vol 5 ◽  
pp. MRI.S10692
Author(s):  
Jonathan D. Thiessen ◽  
Trevor J. Vincent ◽  
Sheryl L. Herrera ◽  
Melanie Martin
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Pulse Sequence ◽  
Spin Echo ◽  
Mean Diffusivity ◽  
Simulated Data ◽  
B Value ◽  
Diffusion Time ◽  
Simulation Data

MRI and Monte Carlo simulated data of pulsed gradient spin echo experiments were used to study the effects of diffusion time, gradient strength and b-value on diffusion tensor (DT) metrics using real and simulated fixed rat spines. Radial (λ⊥) in grey matter and simulation data, axial (λ||) in both grey and white matter in fixed rat spinal cords and mean diffusivity in all tissues showed a significant decrease with diffusion time at b = 1 μm2/ms. All diffusivities significantly decreased with b-value at g = 116 mT/m and at Δeff = 23 ms. The fractional anisotropy (FA) significantly increased with diffusion time at b = 1 μm2/ms in the simulation data and grey matter. FA significantly increased in white matter and simulation data and significantly decreased in grey matter with b-value at g = 116 mT/m and at Δeff = 23 ms. These data suggest that DTI metrics are highly dependent on pulse sequence parameters.

scholarly journals Quantification of alterations in diffusion measures of white matter integrity associated with healthy aging

2019 ◽  
Author(s):  
Ciara J. Molloy ◽  
Sinead Nugent ◽  
Arun L.W. Bokde
Keyword(s):  
White Matter ◽  
Linear Correlation ◽  
Healthy Aging ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
B Value ◽  
Brain Functioning ◽  
Negative Linear Correlation ◽  
Positive Linear Correlation ◽  
The Brain

AbstractThis study aimed to evaluate the linear association of age with diffusion tensor imaging (DTI) measures of white matter such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We assessed patterns of overlap between linear correlations of age with FA with RD, MD and AD to characterize the process of white matter degeneration observed with ageing. 79 healthy adults aged between 18 and 75 took part in the study. The DTI data were based on 61 directions acquired with a b-value of 2000. There was a statistically significant negative linear correlation of age with FA and AD and a positive linear correlation with RD and MD, and AD. The forceps minor tract showed largest percentage of voxels with an association of age with FA, RD and AD, and the anterior thalamic radiation with MD. We found 5 main patterns of overlap: FA alone (15.95%); FA and RD (31.90%); FA and AD (12.99%); FA, RD and AD (27.37%); FA RD, and MD (6.94%). Patterns of overlap between diffusion measures may reflect underlying biological changes with healthy ageing such as loss of myelination, axonal damage, as well as mild microstructural and chronic white matter impairments. This study may provide information about causes of degeneration in specific regions of the brain, and how this may affect healthy brain functioning in older adults.

scholarly journals Brain Reserve in a Case of Cognitive Resilience to Severe Leukoaraiosis

2020 ◽  
pp. 1-10
Author(s):  
Dana M. Szeles ◽  
Nicholas J. Milano ◽  
Hunter J. Moss ◽  
Maria Vittoria Spampinato ◽  
Jens H. Jensen ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Diffusion Tensor ◽  
Imaging Finding ◽  
B Value ◽  
Brain Reserve ◽  
High B Value ◽  
Positive Antibody ◽  
The Face ◽  
Magnetic Resonance Imaging Mri

Abstract Objective: Leukoaraiosis, or white matter rarefaction, is a common imaging finding in aging and is presumed to reflect vascular disease. When severe in presentation, potential congenital or acquired etiologies are investigated, prompting referral for neuropsychological evaluation in addition to neuroimaging. T2-weighted imaging is the most common magnetic resonance imaging (MRI) approach to identifying white matter disease. However, more advanced diffusion MRI techniques may provide additional insight into mechanisms that influence the abnormal T2 signal, especially when clinical presentations are discrepant with imaging findings. Method: We present a case of a 74-year-old woman with severe leukoaraoisis. She was examined by a neurologist, neuropsychologist, and rheumatologist, and completed conventional (T1, T2-FLAIR) MRI, diffusion tensor imaging (DTI), and advanced single-shell, high b-value diffusion MRI (i.e., fiber ball imaging [FBI]). Results: The patient was found to have few neurological signs, no significant cognitive impairment, a negative workup for leukoencephalopathy, and a positive antibody for Sjogren’s disease for which her degree of leukoaraiosis would be highly atypical. Tractography results indicate intact axonal architecture that was better resolved using FBI rather than DTI. Conclusions: This case illustrates exceptional cognitive resilience in the face of severe leukoaraiosis and the potential for advanced diffusion MRI to identify brain reserve.

Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Arterial Stiffness ◽  
Cognitive Decline ◽  
Sex Education ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Injury ◽  
White Matter Integrity ◽  
Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

Diffusion tensor imaging analysis in scrub typhus meningoencephalitis to determine the alteration of microstructural subcortical white-matter integrity

2020 ◽  
pp. 197140092098031
Author(s):  
Pranjal Phukan ◽  
Kalyan Sarma ◽  
Aman Yusuf Khan ◽  
Bhupen Barman ◽  
Md Jamil ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Scrub Typhus ◽  
Diffusion Tensor ◽  
Neuronal Degeneration ◽  
Central Nervous System Involvement ◽  
Subcortical White Matter ◽  
White Matter Integrity ◽  
Conventional Mri ◽  
Significant Difference

Background and purpose Magnetic resonance imaging (MRI) of the brain in scrub typhus meningoencephalitis is non-specific, and in the majority of the cases, conventional MRI fails to detect any abnormality. However, autopsy reports depict central nervous system involvement in almost all patients. There is therefore a need for research on the quantitative assessment of brain parenchyma that can detect microstructural abnormalities. The study aimed to assess the microstructural integrity changes of scrub typhus meningoencephalitis by using different diffusion tensor imaging (DTI) parameters. Methods This was a retrospective analysis of scrub typhus meningoencephalitis. Seven patients and seven age- and sex-matched healthy controls were included. Different DTI parameters such as apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), trace, volume ratio (VR) and geodesic anisotropy (GA) were obtained from six different regions of subcortical white matter at the level of the centrum semiovale. Intergroup significant difference was determined by one-way analysis of variance followed by Tukey’s post hoc test. Receiver operating characteristic curves were constructed to determine the accuracy of the DTI matrices. Results There was a significant decrease in FA, RA and GA as well as an increase in ADC and VR in the subcortical white matter in patients with scrub typhus meningoencephalitis compared to controls ( p < 0.001). The maximum sensitivity of the DTI parameters was 85.7%, and the maximum specificity was 81%. Conclusion There was an alteration of subcortical white-matter integrity in scrub typhus meningoencephalitis that represents the axonal degeneration, myelin breakdown and neuronal degeneration. DTI may be a useful tool to detect white-matter abnormalities in scrub typhus meningoencephalitis in clinical practice, particularly in patients with negative conventional MRI.

scholarly journals White matter network damage mediates association between cerebrovascular disease and cognition

2021 ◽  
pp. 0271678X2199098
Author(s):  
Saima Hilal ◽  
Siwei Liu ◽  
Tien Yin Wong ◽  
Henri Vrooman ◽  
Ching-Yu Cheng ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebrovascular Disease ◽  
Verbal Memory ◽  
Visual Memory ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Domain Specific ◽  
Epidemiology Of Dementia ◽  
Z Scores ◽  
White Matter Connectivity

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

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