scholarly journals White matter integrity correlates with cognition and disease severity in Fabry disease

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3331-3342
Author(s):  
Leonardo Ulivi ◽  
Baris Kanber ◽  
Ferran Prados ◽  
Indran Davagnanam ◽  
Aine Merwick ◽  
...  
Keyword(s):  
White Matter ◽  
Fabry Disease ◽  
Disease Severity ◽  
Fractional Anisotropy ◽  
Processing Speed ◽  
White Matter Hyperintensities ◽  
Mean Diffusivity ◽  
Healthy Controls ◽  
Healthy Control ◽  
The Mean

Abstract Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42–81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10−6 mm2/s (SD 32 × 10−6) versus 720 × 10−6 mm2/s (SD 21 × 10−6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10−6 mm2/s (SD 26 × 10−6) versus 723 × 10−6 mm2/s (SD 22 × 10−6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = −0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = −0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology

Brain ◽  
2020 ◽  
Author(s):  
Ermelinda De Meo ◽  
Loredana Storelli ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
Pierangelo Veggiotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Paediatric Multiple Sclerosis ◽  
Multiple Sclerosis Patients

Abstract The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics—including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio—in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183–0.369; P range = 0.010–0.046), while we found significant mean diffusivity (f2 range = 0.101–0.369; P range = 0.018–0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = −0.27–0.34; P range = 0.004–0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24–0.27; P range = 0.006–0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

scholarly journals Dysmature superficial white matter microstructure in developmental focal epilepsy

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Lauren M Ostrowski ◽  
Daniel Y Song ◽  
Emily L Thorn ◽  
Erin E Ross ◽  
Sally M Stoyell ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Fine Motor ◽  
Epilepsy Syndrome ◽  
Healthy Controls ◽  
Deep White Matter ◽  
White Matter Microstructure ◽  
Benign Epilepsy

Abstract Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.

Mapping white matter damage distribution in neuromyelitis optica spectrum disorders with a multimodal MRI approach

2020 ◽  
pp. 135245852094149
Author(s):  
Laura Cacciaguerra ◽  
Maria A Rocca ◽  
Loredana Storelli ◽  
Marta Radaelli ◽  
Massimo Filippi
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Neuromyelitis Optica ◽  
Mean Diffusivity ◽  
Healthy Controls ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
White Matter Damage ◽  
Axial Diffusivity ◽  
Spectrum Disorders

Background: The pathogenetic mechanisms sustaining neuroinflammatory disorders may originate from the cerebrospinal fluid. Objective: To evaluate white matter damage with diffusion tensor imaging and T1/T2-weighted ratio at progressive distances from the ventricular system in neuromyelitis optica spectrum disorders and multiple sclerosis. Methods: Fractional anisotropy, mean, axial, and radial diffusivity and T1/T2-weighted ratio maps were obtained from patients with seropositive neuromyelitis optica spectrum disorders, multiple sclerosis, and healthy controls ( n = 20 each group). White matter damage was assessed as function of ventricular distance within progressive concentric bands. Results: Compared to healthy controls, neuromyelitis optica spectrum disorders patients had similar fractional anisotropy, radial and axial diffusivity, increased mean diffusivity ( p = 0.009–0.013) and reduced T1/T2-weighted ratio ( p = 0.024–0.037) in all bands. In multiple sclerosis, gradient of percentage lesion volume and intra-lesional mean and axial diffusivity were higher in periventricular bands. Compared to healthy controls, multiple sclerosis patients had reduced fractional anisotropy ( p = 0.001–0.043) in periventricular bands, increased mean ( p < 0.001), radial ( p < 0.001–0.004), and axial diffusivity ( p = 0.002–0.008) and preserved T1/T2-weighted ratio in all bands. Conclusion: White matter damage is higher at periventricular level in multiple sclerosis and diffuse in neuromyelitis optica spectrum disorders. Fractional anisotropy preservation, associated with increased mean diffusivity and reduced T1/T2-weighted ratio may reflect astrocyte damage.

scholarly journals Cognitive Function and 3-Tesla Magnetic Resonance Imaging Tractography of White Matter Hyperintensities in Elderly Persons

2015 ◽  
Vol 5 (3) ◽  
pp. 387-394 ◽  
Author(s):  
William Reginold ◽  
Angela C. Luedke ◽  
Angela Tam ◽  
Justine Itorralba ◽  
Juan Fernandez-Ruiz ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cognitive Function ◽  
White Matter ◽  
Magnetic Resonance ◽  
Fractional Anisotropy ◽  
White Matter Hyperintensities ◽  
Mean Diffusivity ◽  
Elderly Persons ◽  
Resonance Imaging ◽  
Wechsler Memory Scale

Background/Aims: This study used 3-Tesla magnetic resonance imaging (MRI) tractography to determine if there was an association between tracts crossing white matter hyperintensities (WMH) and cognitive function in elderly persons. Methods: Brain T2-weighted fluid-attenuated inversion recovery (FLAIR) and diffusion tensor MRI scans were acquired in participants above the age of 60 years. Twenty-six persons had WMH identified on T2 FLAIR scans. They completed a battery of neuropsychological tests and were classified as normal controls (n = 15) or with Alzheimer's dementia (n = 11). Tractography was generated by the Fiber Assignment by Continuous Tracking method. All tracts that crossed WMH were segmented. The average fractional anisotropy and average mean diffusivity of these tracts were quantified. We studied the association between cognitive test scores with the average mean diffusivity and average fractional anisotropy of tracts while controlling for age, total WMH volume and diagnosis. Results: An increased mean diffusivity of tracts crossing WMH was associated with worse performance on the Wechsler Memory Scale-III Longest Span Forward (p = 0.02). There was no association between the fractional anisotropy of tracts and performance on cognitive testing. Conclusion: The mean diffusivity of tracts crossing WMH measured by tractography is a novel correlate of performance on the Wechsler Memory Scale-III Longest Span Forward in elderly persons.

Increased fractional anisotropy in cerebellum in obsessive–compulsive disorder

2015 ◽  
Vol 28 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Tue Hartmann ◽  
Sanne Vandborg ◽  
Raben Rosenberg ◽  
Leif Sørensen ◽  
Poul Videbech
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Fractional Anisotropy ◽  
White Matter Hyperintensities ◽  
Diffusion Tensor ◽  
Healthy Controls ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
And Diffusion ◽  
Fractional Anisotrophy

BackgroundPrevious morphology and diffusion-imaging studies have suggested that structural changes in white matter is an important part of the pathophysiology of obsessive–compulsive disorder (OCD). However, different methodological approaches and the heterogeneity of patient samples question the validity of the findings.Materials and methodsIn total, 30 patients were matched for age and sex with 30 healthy controls. All participants underwent T1-weighted magnetic resonance imaging, diffusion tensor imaging and T2 fluid-attenuated inversion recovery. Voxel-based morphometry and tract-based spatial statistics were used to compare white matter volumes and diffusion tensor imaging between groups. These data were analysed correcting for the effects of multiple comparisons, age, sex, severity and duration of illness as nuisance covariates. White matter hyperintensities were manually identified.ResultsIncrease in fractional anisotropy in cerebellum was the most prominent result. A decrease in fractional anisotrophy in patients comparable with previous studies was located in forceps minor. There were no differences in the white matter morphology or in the white matter hyperintensities between patients and healthy controls.ConclusionDecrease in fractional anisotrophy in forceps minor and increase in cerebellum were found, and they were not due to neither white matter hyperintensities nor morphology of the white matter. Cerebellar hyperconnectivity could be an important part of OCD pathophysiology.

scholarly journals White matter tract integrity in treatment-resistant gambling disorder

2016 ◽  
Vol 208 (6) ◽  
pp. 579-584 ◽  
Author(s):  
Samuel R. Chamberlain ◽  
Katherine Derbyshire ◽  
Richard E. Daws ◽  
Brian L. Odlaug ◽  
Eric W. Leppink ◽  
...  
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Disease Severity ◽  
Fractional Anisotropy ◽  
Gambling Disorder ◽  
White Matter Integrity ◽  
Future Research ◽  
Healthy Controls ◽  
Treatment Resistant ◽  
Addictive Disorders

BackgroundGambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders'.AimsTo compare white matter integrity in patients with gambling disorder with healthy controls; to explore relationships between white matter integrity and disease severity in gambling disorder.MethodIn total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics.ResultsGambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity.ConclusionsReduced corpus callosum fractional anisotropy is suggestive of disorganised/damaged tracts in patients with gambling disorder, and this may represent a trait/vulnerability marker for the disorder. Future research should explore these measures in a larger sample, ideally incorporating a range of imaging markers (for example functional MRI) and enrolling unaffected first-degree relatives of patients.

Altered Functional Connectivity Patterns of Parietal Subregions Contribute to Cognitive Dysfunction in Patients with White Matter Hyperintensities

2021 ◽  
pp. 1-11
Author(s):  
Qiang Wei ◽  
Shanshan Cao ◽  
Yang Ji ◽  
Jun Zhang ◽  
Chen Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Functional Connectivity ◽  
White Matter Hyperintensities ◽  
Parietal Lobe ◽  
Small Vessel Disease ◽  
Anterior Cingulate ◽  
Healthy Controls ◽  
Cingulate Gyrus ◽  
Anterior Cingulate Gyrus ◽  
Resting State Functional Connectivity

Background: The white matter hyperintensities (WMHs) are considered as one of the core neuroimaging findings of cerebral small vessel disease and independently associated with cognitive deficit. The parietal lobe is a heterogeneous area containing many subregions and play an important role in the processes of neurocognition. Objective: To explore the relationship between parietal subregions alterations and cognitive impairments in WHMs. Methods: Resting-state functional connectivity (rs-FC) analyses of parietal subregions were performed in 104 right-handed WMHs patients divided into mild (n = 39), moderate (n = 37), and severe WMHs (n = 28) groups according to the Fazekas scale and 36 healthy controls. Parietal subregions were defined using tractographic Human Brainnetome Atlas and included five subregions for superior parietal lobe, six subregions for inferior parietal lobe (IPL), and three subregions for precuneus. All participants underwent a neuropsychological test battery to evaluate emotional and general cognitive functions. Results: Differences existed between the rs-FC strength of IPL_R_6_2 with the left anterior cingulate gyrus, IPL_R_6_3 with the right dorsolateral superior frontal gyrus, and the IPL_R_6_5 with the left anterior cingulate gyrus. The connectivity strength between IPL_R_6_3 and the left anterior cingulate gyrus were correlated with AVLT-immediate and AVLT-recognition test in WMHs. Conclusion: We explored the roles of parietal subregions in WMHs using rs-FC. The functional connectivity of parietal subregions with the cortex regions showed significant differences between the patients with WMHs and healthy controls which may be associated with cognitive deficits in WMHs.

scholarly journals A Correlational Study between Microstructural White Matter Properties and Macrostructural Gray Matter Volume Across Normal Ageing: Conjoint DTI and VBM Analysis

2018 ◽  
Vol 11 ◽  
pp. 1178623X1879992 ◽  
Author(s):  
Vikas Pareek ◽  
VP Subramanyam Rallabandi ◽  
Prasun K Roy
Keyword(s):  
White Matter ◽  
Life Span ◽  
Fractional Anisotropy ◽  
Gray Matter ◽  
Healthy Aging ◽  
Gray Matter Volume ◽  
Mean Diffusivity ◽  
Radial Diffusivity ◽  
Axial Diffusivity ◽  
Matter Volume

We investigate the relationship between Gray matter’s volume vis-a-vis White matter’s integrity indices, such Axial diffusivity, Radial diffusivity, Mean diffusivity, and Fractional anisotropy, in individuals undergoing healthy aging. We investigated MRI scans of 177 adults across 20 to 85 years. We used Voxel-based morphometry, and FDT-FSL analysis for estimation of Gray matter volume and White matter’s diffusion indices respectively. Across the life span, we observed an inter-relationship between the Gray matter and White matter, namely that both Axial diffusivity and Mean Diffusivity show strong correlation with Gray matter volume, along the aging process. Furthermore, across all ages the Fractional anisotropy and Mean diffusivity are found to be significantly reduced in females when compared to males, but there are no significant gender differences in Axial Diffusivity and Radial diffusivity. We conclude that for both genders across all ages, the Gray matter’s Volume is strongly correlated with White matter’s Axial Diffusivity and Mean Diffusivity, while being weakly correlated with Fractional Anisotropy. Our study clarifies the multi-scale relationship in brain tissue, by elucidating how the White matter’s micro-structural parameters influences the Gray matter’s macro-structural characteristics, during healthy aging across the life-span.

scholarly journals White matter differences between essential tremor and Parkinson disease

Neurology ◽  
2018 ◽  
Vol 92 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Meher R. Juttukonda ◽  
Giulia Franco ◽  
Dario J. Englot ◽  
Ya-Chen Lin ◽  
Kalen J. Petersen ◽  
...  
Keyword(s):  
White Matter ◽  
Parkinson Disease ◽  
Essential Tremor ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Superior Cerebellar Peduncle ◽  
Radial Diffusivity ◽  
Cerebellar Peduncles ◽  
Cerebellar Peduncle

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.

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