Altered microstructure of the splenium of corpus callosum is associated with neurodevelopmental impairment in preterm infants with necrotizing enterocolitis

Abstract Background Necrotizing enterocolitis (NEC) is a devastating disease in preterm infants with significant morbidities, including neurodevelopmental impairment (NDI). This study aimed to investigate whether NEC is associated with (1) brain volume expansion and white matter maturation using diffusion tensor imaging analysis and (2) NDI compared with preterm infants without NEC. Methods We included 86 preterm infants (20 with NEC and 66 without NEC) with no evidence of brain abnormalities on trans-fontanelle ultrasonography and magnetic resonance imaging at term-equivalent age (TEA). Regional brain volume analysis and white matter tractography were performed to study brain microstructure alterations. NDI was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III) at 18 months of corrected age (CA). Results Preterm infants with NEC showed significantly high risk of motor impairment (odds ratio 58.26, 95% confidence interval 7.80–435.12, p < 0.001). We found significantly increased mean diffusivity (MD) in the splenium of corpus callosum (sCC) (p = 0.001) and the left corticospinal tract (p = 0.001) in preterm infants with NEC. The sCC with increased MD showed a negative association with the BSID-III language (p = 0.025) and motor scores (p = 0.002) at 18 months of CA, implying the relevance of sCC integrity with later NDI. Conclusion The white matter microstructure differed between preterm infants with and without NEC. The prognostic value of network parameters of sCC at TEA may provide better information for the early detection of NDI in preterm infants.

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White matter abnormalities in the corpus callosum with cognitive impairment in Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006646 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2244-e2255 ◽

Cited By ~ 16

Author(s):

Ian O. Bledsoe ◽

Glenn T. Stebbins ◽

Doug Merkitch ◽

Jennifer G. Goldman

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Parkinson Disease ◽

Information Transfer ◽

Diffusion Tensor ◽

Anterior Segment ◽

Mean Diffusivity ◽

Cognitive Domain ◽

White Matter Abnormalities

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.

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Maturation of Corpus Callosum Anterior Midbody Is Associated with Neonatal Motor Function in Eight Preterm-Born Infants

Neural Plasticity ◽

10.1155/2013/359532 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 17

Author(s):

Preethi Mathew ◽

Kerstin Pannek ◽

Pamela Snow ◽

M. Giulia D'Acunto ◽

Andrea Guzzetta ◽

...

Keyword(s):

Corpus Callosum ◽

Preterm Infants ◽

Motor Function ◽

Gestational Age ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Motor Impairments ◽

Very Preterm Infants ◽

Very Preterm ◽

Preterm Born

Background. The etiology of motor impairments in preterm infants is multifactorial and incompletely understood. Whether corpus callosum development is related to impaired motor function is unclear. Potential associations between motor-related measures and diffusion tensor imaging (DTI) of the corpus callosum in preterm infants were explored.Methods. Eight very preterm infants (gestational age of 28–32 weeks) underwent the Hammersmith neonatal neurological examination and DTI assessments at gestational age of 42 weeks. The total Hammersmith score and a motor-specific score (sum of Hammersmith motor subcategories) were calculated. Six corpus callosum regions of interest were defined on the mid-sagittal DTI slice—genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. The fractional anisotropy (FA) and mean diffusivity (MD) of these regions were computed, and correlations between these and Hammersmith measures were sought.Results. Anterior midbody FA measures correlated positively with total Hammersmith (rho=0.929,P=0.001) and motor-specific scores (rho=0.857,P=0.007). Total Hammersmith scores also negatively correlated with anterior midbody MD measures (rho=−0.714,P=0.047).Discussion. These results suggest the integrity of corpus callosum axons, particularly anterior midbody axons, is important in mediating neurological functions. Greater callosal maturation was associated with greater motor function. Corpus callosum DTI may prove to be a valuable screening or prognostic marker.

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Corpus Callosum and Cingulum Tractography in Parkinson's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100010751 ◽

2010 ◽

Vol 37 (5) ◽

pp. 595-600 ◽

Cited By ~ 28

Author(s):

Katie Wiltshire ◽

Luis Concha ◽

Myrlene Gee ◽

Thomas Bouchard ◽

Christian Beaulieu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Method ◽

Motor Symptoms ◽

Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

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Magnetic resonance diffusion tensor imaging and tractography of intracranial cavernous malformations: preliminary observations and characterization of the hemosiderin rim

Journal of Neurosurgery ◽

10.3171/2009.8.jns09586 ◽

2010 ◽

Vol 112 (4) ◽

pp. 814-823 ◽

Cited By ~ 17

Author(s):

Keith A. Cauley ◽

Trevor Andrews ◽

Jay V. Gonyea ◽

Christopher G. Filippi

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Mass Effect ◽

Lesion Size ◽

Single Shot ◽

Cavernous Malformations ◽

Central Lesion ◽

White Matter Tractography

Object Cavernous malformations (CMs) can cause symptoms that appear out of proportion to the lesion size, leading one to hypothesize that they may have an effect on adjacent white matter that is not fully explained by local mass effect. The goal of this study was to investigate the diffusion tensor (DT) properties of CMs, the hemosiderin rim, and normal-appearing adjacent white matter. Methods Eighteen cavernous malformations were characterized using standard MR imaging sequences as well as 6-direction DT imaging with single-shot echo planar–gradient echo imaging at 3 tesla. Results Diffusion tensor imaging demonstrated that CMs have a characteristic signature on DT imaging, with low fractional anisotropy (FA) and high mean diffusivity centrally within the lesion. The hemosiderin rim had a high FA value relative to the central lesion or adjacent white matter. Tractography revealed that tracts neatly deviate around CMs. Tracts were typically seen to pass through the hemosiderin rim. Conclusions The hemosiderin rim of CMs was intimately associated with white matter tracts that were deviated by the central lesion. These findings are consistent with histopathological reports that the hemosiderin rim is composed of blood breakdown products deposited in viable white matter.

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Microstructural Neuroimaging of Frailty in Cognitively Normal Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.571 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 176-177

Author(s):

Qu Tian ◽

Susan Resnick ◽

Bennett Landman ◽

Luigi Ferrucci

Keyword(s):

Older Adults ◽

White Matter ◽

Corpus Callosum ◽

Gray Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Carrier Status ◽

Cognitively Normal ◽

Frailty Status ◽

Brain Microstructure

Abstract Physical frailty is an age-related clinical syndrome that is related to adverse health outcomes, including cognitive impairment and dementia. Recent studies have shown structural neuroimaging correlates with frailty. However, most existing evidence relies on brain volumetric measures. Whether brain microstructure is associated with frailty and its spatial distribution have not been explored. In the Baltimore Longitudinal Study of Aging, we identified 776 cognitively normal participants aged 50 and older who had concurrent data on frailty and brain microstructure by diffusion tensor imaging (DTI), including mean diffusivity (MD) of gray matter and fractional anisotropy (FA) of white matter. We first identified neuroimaging markers that were associated with frailty score (0-5) and further examined their relationships with frailty status (0: non-frail, 1-2: pre-frail, 3+: frail) using multivariate linear regression. Models were adjusted for age, sex, race, years of education, and Apolipoprotein E e4 carrier status. DTI-based neuroimaging markers that were associated with frailty status were localized in the supplementary motor area of the frontal lobe, several subcortical regions (putamen, caudate), and body and splenium of corpus callosum. This study demonstrates for the first time that microstructure of both gray and white matter differs by frailty levels in cognitively normal older adults. Brain areas were not widespread, but mostly localized in gray matter subcortical motor areas and white matter corpus callosum. Whether changes in brain microstructure precede future frailty development warrants further investigation.

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Diffusion tensor imaging in hyperthyroidism: assessment of microstructural white matter abnormality with a tract-based spatial statistical analysis

Acta Radiologica ◽

10.1177/0284185120909960 ◽

2020 ◽

Vol 61 (12) ◽

pp. 1677-1683 ◽

Cited By ~ 1

Author(s):

Kerim Aslan ◽

Hediye Pinar Gunbey ◽

Sumeyra Cortcu ◽

Onur Ozyurt ◽

Ugur Avci ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Internal Capsule ◽

Control Group ◽

Corona Radiata ◽

Microstructural Alterations

Background Metabolic, morphological, and functional brain changes associated with a neurological deficit in hyperthyroidism have been observed. However, changes in microstructural white matter (WM), which can explain the underlying pathophysiology of brain dysfunctions, have not been researched. Purpose To assess microstructural WM abnormality in patients with untreated or newly diagnosed hyperthyroidism using tract-based spatial statistics (TBSS). Material and Methods Eighteen patients with hyperthyroidism and 14 age- and sex-matched healthy controls were included in this study. TBSS were used in this diffusion tensor imaging study for a whole-brain voxel-wise analysis of fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD) of WM. Results When compared to the control group, TBSS showed a significant increase in the RD of the corpus callosum, anterior and posterior corona radiata, posterior thalamic radiation, cingulum, superior longitudinal fasciculus, and the retrolenticular region of the internal capsule in patients with hyperthyroidism ( P < 0.05), as well as a significant decrease in AD in the anterior corona radiata and the genu of corpus callosum ( P < 0.05). Conclusion This study showed that more regions are affected by the RD increase than the AD decrease in the WM tracts of patients with hyperthyroidism. These preliminary results suggest that demyelination is the main mechanism of microstructural alterations in the WM of hyperthyroid patients.

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Disconnection as a mechanism for social cognition impairment in multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000004060 ◽

2017 ◽

Vol 89 (1) ◽

pp. 38-45 ◽

Cited By ~ 23

Author(s):

Sonia Batista ◽

Carolina Alves ◽

Otília C. d’Almeida ◽

Ana Afonso ◽

Ricardo Félix-Morais ◽

...

Keyword(s):

Multiple Sclerosis ◽

Social Cognition ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Brain Mri ◽

Mean Diffusivity ◽

Uncinate Fasciculus ◽

Neural Basis ◽

Cognition Impairment

Objective:To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS).Methods:We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM.Results:Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g −1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g −1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus.Conclusions:These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.

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Nitric Oxide Synthase Type 1 Methylation Is Associated With White Matter Microstructure in the Corpus Callosum and Greater Panic Disorder Severity Among Panic Disorder Patients

Frontiers in Neurology ◽

10.3389/fneur.2021.755270 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huazhen Xu ◽

Yuan Zhong ◽

Shiting Yuan ◽

Yun Wu ◽

Zijuan Ma ◽

...

Keyword(s):

Nitric Oxide ◽

White Matter ◽

Nitric Oxide Synthase ◽

Panic Disorder ◽

Corpus Callosum ◽

Symptom Severity ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Mediating Effect ◽

Oxide Synthase

Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding.Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD.Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = −1.731 to −0.034).Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.

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Assessment of White Matter Lesions in Parkinson's Disease: Voxel-based Analysis and Tract-based Spatial Statistics Analysis of Parkinson's Disease with Mild Cognitive Impairment

Current Neurovascular Research ◽

10.2174/1567202617666200901181842 ◽

2020 ◽

Vol 17 (4) ◽

pp. 480-486

Author(s):

Wei Pu ◽

Xudong Shen ◽

Mingming Huang ◽

Zhiqian Li ◽

Xianchun Zeng ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Fractional Anisotropy ◽

Spatial Statistics ◽

Diffusion Tensor ◽

Tract Based Spatial Statistics

Objective: Application of diffusion tensor imaging (DTI) to explore the changes of FA value in patients with Parkinson's disease (PD) with mild cognitive impairment. Methods: 27 patients with PD were divided into PD with mild cognitive impairment (PD-MCI) group (n = 7) and PD group (n = 20). The original images were processed using voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Results: The average age of pd-mci group was longer than that of PD group, and the course of disease was longer than that of PD group. Compared with PD group, the voxel based analysis-fractional anisotropy (VBA-FA) values of PD-MCI group decreased in the following areas: bilateral frontal lobe, bilateral temporal lobe, bilateral parietal lobe, bilateral subthalamic nucleus, corpus callosum, and gyrus cingula. Tract-based spatial statistics-fractional anisotropy (TBSS-FA) values in PD-MCI group decreased in bilateral corticospinal tract, anterior cingulum, posterior cingulum, fornix tract, bilateral superior thalamic radiation, corpus callosum(genu, body and splenium), bilateral uncinate fasciculus, bilateral inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, bilateral superior fronto-occipital fasciculus, bilateral inferior fronto-occipital fasciculus, and bilateral parietal-occipital tracts. The mean age of onset in the PD-MCI group was greater than that in the PD group, and the disease course was longer than that in the PD group. Conclusion: DTI-based VBA and TBSS post-processing methods can detect abnormalities in multiple brain areas and white matter fiber tracts in PD-MCI patients. Impairment of multiple cerebral cortex and white matter fiber pathways may be an important causes of cognitive dysfunction in PD-MCI.

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

Journal of Alzheimer s Disease ◽

10.3233/jad-201424 ◽

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.

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