Global and Targeted Pathway Impact of Gliomas on White Matter Integrity Based on Lobar Localization.

PubMed

Ormond, David R; D'Souza, Shawn; Thompson, John A

2017-09-07

Primary brain tumors comprise 28% of all tumors and 80% of malignant tumors. Pathophysiology of high-grade gliomas includes significant distortion of white matter architecture, necrosis, the breakdown of the blood brain barrier, and increased intracranial pressure. Diffusion tensor imaging (DTI), a diffusion weighted imaging technique, can be used to assess white matter architecture. Use of DTI as a non-invasive pathophysiological tool to analyze glioma impact on white matter microstructure has yet to be fully explored. Preliminary assessment of DTI tractography was done as a measure of intracranial tumor impact on white matter architecture. Specifically, we addressed three questions: 1) whether glioma differentially affects local white matter structure compared to metastasis, 2) whether glioma affects tract integrity of major white matter bundles, 3) whether glioma lobe localization affects tract integrity of different white matter bundles. In this study, we retrospectively investigated preoperative DTI scans from 24 patients undergoing tumor resection. Fiber tractography was estimated using a deterministic fiber tracking algorithm in DSI (diffusion spectrum imaging) Studio. The automatic anatomical labeling (AAL) atlas was used to define the left and right (L/R)   hemisphere regions of interest (ROI). In addition, the John Hopkins University (JHU) White Matter Atlas was used to auto-segment major white matter bundle ROIs. For all tracts derived from ROI seed targets, we computed the following parameters: tract number, tract length, fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The DTI tractography analysis revealed that white matter integrity in the hemisphere ipsilateral to intracranial tumor was significantly compromised compared to the control contralateral hemisphere. No differences were observed between high vs low-grade gliomas, however, gliomas induced significantly greater white matter degradation than metastases. In addition, targeted analysis of major white matter bundles important for sensory/motor function (i.e., corticospinal tract and superior longitudinal fasciculus) revealed tract-parameter specific susceptibility due to the presence of the tumor. Finally, major tract bundles were differentially affected based on lobar localization of the glioma. These DTI-based tractographic analyses complement findings from gross histopathological examination of glioma impact on neural tissue. Global and focal white matter architecture, ipsilateral to glioma, shows higher rates of degradation or edema - based on DTI tractographic metrics - in comparison to normal brain or metastases. Gliomas, which arise in the parietal lobe, also have a higher negative impact (potentially due to increased edema) on white matter integrity of the superior longitudinal fasciculus(SLF) than those which arise in the frontal lobe. Future studies will focus on using preoperative and postoperative tractography to predict functional deficits following resective surgery.

Major Superficial White Matter Abnormalities in Huntington's Disease

PubMed Central

Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

2016-01-01

Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

Altered tract-specific white matter microstructure is related to poorer cognitive performance: The Rotterdam Study.

PubMed

Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Krestin, Gabriel P; van der Lugt, Aad; Niessen, Wiro J; Vernooij, Meike W; Ikram, M Arfan

2016-03-01

White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Design and validation of diffusion MRI models of white matter

NASA Astrophysics Data System (ADS)

Jelescu, Ileana O.; Budde, Matthew D.

2017-11-01

Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus.

Design and validation of diffusion MRI models of white matter

PubMed Central

Jelescu, Ileana O.; Budde, Matthew D.

2018-01-01

Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus. PMID:29755979

White Matter Compromise of Callosal and Subcortical Fiber Tracts in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Lincoln, Alan J.; Muller, Ralph-Axel

2010-01-01

Objective: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle…

Cortical gray and subcortical white matter associations in Parkinson's disease.

PubMed

Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

2017-01-01

Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel white matter tract integrity metrics sensitive to Alzheimer disease progression.

PubMed

Fieremans, E; Benitez, A; Jensen, J H; Falangola, M F; Tabesh, A; Deardorff, R L; Spampinato, M V S; Babb, J S; Novikov, D S; Ferris, S H; Helpern, J A

2013-01-01

Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82-0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80-0.82|, P < .001). These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.

Altered white matter in early visual pathways of humans with amblyopia.

PubMed

Allen, Brian; Spiegel, Daniel P; Thompson, Benjamin; Pestilli, Franco; Rokers, Bas

2015-09-01

Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans.

PubMed

Chao, Linda L; Zhang, Yu; Buckley, Shannon

2015-05-01

We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity. Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status. There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure. The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans with predicted GB/GF exposure hint at the possibility that the widespread increases in axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed controls may reflect white matter reorganization after brain injury (i.e., exposure to GB/GF). Published by Elsevier B.V.

Surface-based reconstruction and diffusion MRI in the assessment of gray and white matter damage in multiple sclerosis

NASA Astrophysics Data System (ADS)

Caffini, Matteo; Bergsland, Niels; LaganÃ, Marcella; Tavazzi, Eleonora; Tortorella, Paola; Rovaris, Marco; Baselli, Giuseppe

2014-03-01

Despite advances in the application of nonconventional MRI techniques in furthering the understanding of multiple sclerosis pathogenic mechanisms, there are still many unanswered questions, such as the relationship between gray and white matter damage. We applied a combination of advanced surface-based reconstruction and diffusion tensor imaging techniques to address this issue. We found significant relationships between white matter tract integrity indices and corresponding cortical structures. Our results suggest a direct link between damage in white and gray matter and contribute to the notion of gray matter loss relating to clinical disability.

Spaceflight Effect on White Matter Structural Integrity

NASA Technical Reports Server (NTRS)

Lee, Jessica K.; Kopplemans, Vincent; Paternack, Ofer; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

2017-01-01

Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in postflight astronaut MRIs suggest that further examination of spaceflight's impact on the microstructure of brain white matter is warranted. To this end, retrospective longitudinal diffusion-weighted MRI scans obtained from 15 astronauts were evaluated. In light of the recent reports of microgravity-induced cephalad fluid shift and gray matter atrophy seen in astronauts, we applied a technique to estimate diffusion tensor imaging (DTI) metrics corrected for free water contamination. This approach enabled the analysis of white matter tissue-specific alterations that are unrelated to fluid shifts, occurring from before spaceflight to after landing. After spaceflight, decreased fractional anisotropy (FA) values were detected in an area encompassing the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus. Increased radial diffusivity (RD) and decreased axial diffusivity (AD) were also detected within overlapping regions. In addition, FA values in the corticospinal tract decreased and RD measures in the precentral gyrus white matter increased from before to after flight. The results show disrupted structural connectivity of white matter in tracts involved in visuospatial processing, vestibular function, and movement control as a result of spaceflight. The findings may help us understand the structural underpinnings of the extensive spaceflight-induced sensorimotor remodeling. Prospective longitudinal assessment of the white matter integrity in astronauts is needed to characterize the evolution of white matter microstructural changes associated with spaceflight, their behavioral consequences, and the time course of recovery. Supported by a grant from the National Space Biomedical Research Institute, NASA NCC 9-58.

Retinal microvasculature and white matter microstructure: The Rotterdam Study.

PubMed

Mutlu, Unal; Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Klaver, Caroline C W; Ikram, M Arfan; Vernooij, Meike W; Ikram, M Kamran

2016-09-06

To investigate whether retinal microvascular damage is related to normal-appearing white matter microstructure on diffusion tensor MRI. We included 2,436 participants (age ≥45 years) from the population-based Rotterdam Study (2005-2009) who had gradable retinal images and brain MRI scans. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. White matter microstructure was assessed using diffusion tensor MRI. We used linear regression models to investigate the associations of retinal vascular calibers with markers of normal-appearing white matter microstructure, adjusting for age, sex, the fellow vascular caliber, and additionally for structural MRI markers and cardiovascular risk factors. Narrower arterioles and wider venules were associated with poor white matter microstructure: adjusted difference in fractional anisotropy per SD decrease in arteriolar caliber -0.061 (95% confidence interval -0.106 to -0.016), increase in venular caliber -0.054 (-0.096 to -0.011), adjusted difference in mean diffusivity per SD decrease in arteriolar caliber 0.048 (0.007-0.088), and increase in venular caliber 0.047 (0.008-0.085). The associations for venules were more prominent in women. Retinal vascular calibers are related to normal-appearing white matter microstructure. This suggests that microvascular damage in the white matter is more widespread than visually detectable as white matter lesions. © 2016 American Academy of Neurology.

Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents

PubMed Central

Ben-Shachar, Michal; Feldman, Heidi M.

2015-01-01

Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood. PMID:26560745

Experience-dependent plasticity in white matter microstructure: reasoning training alters structural connectivity

PubMed Central

Mackey, Allyson P.; Whitaker, Kirstie J.; Bunge, Silvia A.

2012-01-01

Diffusion tensor imaging (DTI) techniques have made it possible to investigate white matter plasticity in humans. Changes in DTI measures, principally increases in fractional anisotropy (FA), have been observed following training programs as diverse as juggling, meditation, and working memory. Here, we sought to test whether three months of reasoning training could alter white matter microstructure. We recruited participants (n = 23) who were enrolled in a course to prepare for the Law School Admission Test (LSAT), a test that places strong demands on reasoning skills, as well as age- and IQ-matched controls planning to take the LSAT in the future (n = 22). DTI data were collected at two scan sessions scheduled three months apart. In trained participants but not controls, we observed decreases in radial diffusivity (RD) in white matter connecting frontal cortices, and in mean diffusivity (MD) within frontal and parietal lobe white matter. Further, participants exhibiting larger gains on the LSAT exhibited greater decreases in MD in the right internal capsule. In summary, reasoning training altered multiple measures of white matter structure in young adults. While the cellular underpinnings are unknown, these results provide evidence of experience-dependent white matter changes that may not be limited to myelination. PMID:22936899

Full Tensor Diffusion Imaging Is Not Required To Assess the White-Matter Integrity in Mouse Contusion Spinal Cord Injury

PubMed Central

Tu, Tsang-Wei; Kim, Joong H.; Wang, Jian

2010-01-01

Abstract In vivo diffusion tensor imaging (DTI) derived indices have been demonstrated to quantify accurately white-matter injury after contusion spinal cord injury (SCI) in rodents. In general, a full diffusion tensor analysis requires the acquisition of diffusion-weighted images (DWI) along at least six independent directions of diffusion-sensitizing gradients. Thus, DTI measurements of the rodent central nervous system are time consuming. In this study, diffusion indices derived using the two-direction DWI (parallel and perpendicular to axonal tracts) were compared with those obtained using six-direction DTI in a mouse model of SCI. It was hypothesized that the mouse spinal cord ventral-lateral white-matter (VLWM) tracts, T8–T10 in this study, aligned with the main magnet axis (z) allowing the apparent diffusion coefficient parallel and perpendicular to the axis of the spine to be derived with diffusion-weighting gradients in the z and y axes of the magnet coordinate respectively. Compared with six-direction full tensor DTI, two-direction DWI provided comparable diffusion indices in mouse spinal cords. The measured extent of spared white matter after injury, estimated by anisotropy indices, using both six-direction DTI and two-direction DWI were in close agreement and correlated well with histological staining and behavioral assessment. The results suggest that the two-direction DWI derived indices may be used, with significantly reduced imaging time, to estimate accurately spared white matter in mouse SCI. PMID:19715399

Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke.

PubMed

Etherton, Mark R; Wu, Ona; Cougo, Pedro; Giese, Anne-Katrin; Cloonan, Lisa; Fitzpatrick, Kaitlin M; Kanakis, Allison S; Boulouis, Gregoire; Karadeli, Hasan H; Lauer, Arne; Rosand, Jonathan; Furie, Karen L; Rost, Natalia S

2017-12-01

Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P =0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P =0.04), and lower rate of tobacco use (21.1% versus 35.9%; P =0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score <2: 49.6% versus 67.0%; P =0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism. © 2017 American Heart Association, Inc.

Lower Orbital Frontal White Matter Integrity in Adolescents with Bipolar I Disorder

ERIC Educational Resources Information Center

Kafantaris, Vivian; Kingsley, Peter; Ardekani, Babak; Saito, Ema; Lencz, Todd; Lim, Kelvin; Szeszko, Philip

2009-01-01

Patients with bipolar I disorder demonstrated white matter abnormalities in white matter regions as seen through the use of diffusion tensor imaging. The findings suggest that white matter abnormalities in pediatric bipolar disorder may be useful in constructing neurobiological models of the disorder.

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

Whole brain white matter connectivity analysis using machine learning: An application to autism.

PubMed

Zhang, Fan; Savadjiev, Peter; Cai, Weidong; Song, Yang; Rathi, Yogesh; Tunç, Birkan; Parker, Drew; Kapur, Tina; Schultz, Robert T; Makris, Nikos; Verma, Ragini; O'Donnell, Lauren J

2018-05-15

In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering. Copyright © 2017 Elsevier Inc. All rights reserved.

Characteristics of early MRI in children and adolescents with vanishing white matter.

PubMed

van der Lei, Hannemieke D; Steenweg, Marjan E; Barkhof, Frederik; de Grauw, Ton; d'Hooghe, Marc; Morton, Richard; Shah, Siddharth; Wolf, Nicole; van der Knaap, Marjo S

2012-02-01

MRI in vanishing white matter typically shows diffuse abnormality of the cerebral white matter, which becomes increasingly rarefied and cystic. We investigated the MRI characteristics preceding this stage. In a retrospective observational study, we evaluated all available MRIs in our database of DNA-confirmed VWM patients and selected MRIs without diffuse cerebral white matter abnormalities and without signs of rarefaction or cystic degeneration in patients below 20 years of age. A previously established scoring list was used to evaluate the MRIs. An MRI of seven patients fulfilled the criteria. All had confluent and symmetrical abnormalities in the periventricular and bordering deep white matter. In young patients, myelination was delayed. The inner rim of the corpus callosum was affected in all patients. In early stages of VWM, MRI does not necessarily display diffuse cerebral white matter involvement and rarefaction or cystic degeneration. If the MRI abnormalities do not meet the criteria for VWM, it helps to look at the corpus callosum. If the inner rim (the callosal-septal interface) is affected, VWM should be considered. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain

PubMed Central

Chanraud, Sandra; Zahr, Natalie; Pfefferbaum, Adolf

2010-01-01

As Norman Geschwind asserted in 1965, syndromes resulting from white matter lesions could produce deficits in higher-order functions and “disconnexion” or the interruption of connection between gray matter regions could be as disruptive as trauma to those regions per se. The advent of in vivo diffusion tensor imaging, which allows quantitative characterization of white matter fiber integrity in health and disease, has served to strengthen Geschwind's proposal. Here we present an overview of the principles of diffusion tensor imaging (DTI) and its contribution to progress in our current understanding of normal and pathological brain function. PMID:20422451

Quantitative validation of a nonlinear histology-MRI coregistration method using Generalized Q-sampling Imaging in complex human cortical white matter

PubMed Central

Gangolli, Mihika; Holleran, Laurena; Kim, Joong Hee; Stein, Thor D.; Alvarez, Victor; McKee, Ann C.; Brody, David L.

2017-01-01

Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images. When validated in ex vivo human cortical tissue at a 250 × 250 × 500 micron spatial resolution, the method proved robust in correlations between generalized q-sampling imaging and histologically based white matter fiber orientations, with r = 0.94 for the primary fiber direction and r = 0.88 for secondary fiber direction in each voxel. Importantly, however, the correlation was substantially worse with reduced spatial resolution or with fiber orientations derived using a diffusion tensor model. Furthermore, we have detailed a quantitative histological metric of white matter fiber integrity termed power coherence capable of distinguishing between architecturally complex but intact white matter from disrupted white matter regions. These methods may allow for more sensitive and specific radiological-pathological correlations of neurodegenerative diseases affecting complex gray and white matter. PMID:28365421

White matter tractography using diffusion tensor deflection.

PubMed

Lazar, Mariana; Weinstein, David M; Tsuruda, Jay S; Hasan, Khader M; Arfanakis, Konstantinos; Meyerand, M Elizabeth; Badie, Benham; Rowley, Howard A; Haughton, Victor; Field, Aaron; Alexander, Andrew L

2003-04-01

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Copyright 2003 Wiley-Liss, Inc.

Improving the realism of white matter numerical phantoms: a step towards a better understanding of the influence of structural disorders in diffusion MRI

NASA Astrophysics Data System (ADS)

Ginsburger, Kévin; Poupon, Fabrice; Beaujoin, Justine; Estournet, Delphine; Matuschke, Felix; Mangin, Jean-François; Axer, Markus; Poupon, Cyril

2018-02-01

White matter is composed of irregularly packed axons leading to a structural disorder in the extra-axonal space. Diffusion MRI experiments using oscillating gradient spin echo sequences have shown that the diffusivity transverse to axons in this extra-axonal space is dependent on the frequency of the employed sequence. In this study, we observe the same frequency-dependence using 3D simulations of the diffusion process in disordered media. We design a novel white matter numerical phantom generation algorithm which constructs biomimicking geometric configurations with few design parameters, and enables to control the level of disorder of the generated phantoms. The influence of various geometrical parameters present in white matter, such as global angular dispersion, tortuosity, presence of Ranvier nodes, beading, on the extra-cellular perpendicular diffusivity frequency dependence was investigated by simulating the diffusion process in numerical phantoms of increasing complexity and fitting the resulting simulated diffusion MR signal attenuation with an adequate analytical model designed for trapezoidal OGSE sequences. This work suggests that angular dispersion and especially beading have non-negligible effects on this extracellular diffusion metrics that may be measured using standard OGSE DW-MRI clinical protocols.

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

PubMed

Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel

2015-05-01

Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigating the capability to resolve complex white matter structures with high b-value diffusion magnetic resonance imaging on the MGH-USC Connectom scanner.

PubMed

Fan, Qiuyun; Nummenmaa, Aapo; Witzel, Thomas; Zanzonico, Roberta; Keil, Boris; Cauley, Stephen; Polimeni, Jonathan R; Tisdall, Dylan; Van Dijk, Koene R A; Buckner, Randy L; Wedeen, Van J; Rosen, Bruce R; Wald, Lawrence L

2014-11-01

One of the major goals of the NIH Blueprint Human Connectome Project was to map and quantify the white matter connections in the brain using diffusion tractography. Given the prevalence of complex white matter structures, the capability of resolving local white matter geometries with multiple crossings in the diffusion magnetic resonance imaging (dMRI) data is critical. Increasing b-value has been suggested for delineation of the finer details of the orientation distribution function (ODF). Although increased gradient strength and duration increase sensitivity to highly restricted intra-axonal water, gradient strength limitations require longer echo times (TE) to accommodate the increased diffusion encoding times needed to achieve a higher b-value, exponentially lowering the signal-to-noise ratio of the acquisition. To mitigate this effect, the MGH-USC Connectom scanner was built with 300 mT/m gradients, which can significantly reduce the TE of high b-value diffusion imaging. Here we report comparisons performed across b-values based on q-ball ODF metrics to investigate whether high b-value diffusion imaging on the Connectom scanner can improve resolving complex white matter structures. The q-ball ODF features became sharper as the b-value increased, with increased power fraction in higher order spherical harmonic series of the ODF and increased peak heights relative to the overall size of the ODF. Crossing structures were detected in an increasingly larger fraction of white matter voxels and the spatial distribution of two-way and three-way crossing structures was largely consistent with known anatomy. Results indicate that dMRI with high diffusion encoding on the Connectom system is a promising tool to better characterize, and ultimately understand, the underlying structural organization and motifs in the human brain.

Age-related decline in task switching is linked to both global and tract-specific changes in white matter microstructure.

PubMed

Jolly, Todd A D; Cooper, Patrick S; Rennie, Jaime L; Levi, Christopher R; Lenroot, Rhoshel; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

2017-03-01

Task-switching performance relies on a broadly distributed frontoparietal network and declines in older adults. In this study, they investigated whether this age-related decline in task switching performance was mediated by variability in global or regional white matter microstructural health. Seventy cognitively intact adults (43-87 years) completed a cued-trials task switching paradigm. Microstructural white matter measures were derived using diffusion tensor imaging (DTI) analyses on the diffusion-weighted imaging (DWI) sequence. Task switching performance decreased with increasing age and radial diffusivity (RaD), a measure of white matter microstructure that is sensitive to myelin structure. RaD mediated the relationship between age and task switching performance. However, the relationship between RaD and task switching performance remained significant when controlling for age and was stronger in the presence of cardiovascular risk factors. Variability in error and RT mixing cost were associated with RaD in global white matter and in frontoparietal white matter tracts, respectively. These findings suggest that age-related increase in mixing cost may result from both global and tract-specific disruption of cerebral white matter linked to the increased incidence of cardiovascular risks in older adults. Hum Brain Mapp 38:1588-1603, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Altering cortical connectivity: Remediation-induced changes in the white matter of poor readers

PubMed Central

Keller, Timothy A.; Just, Marcel Adam

2009-01-01

SUMMARY Neuroimaging studies using diffusion tensor imaging (DTI) have revealed regions of cerebral white matter with decreased microstructural organization (lower fractional anisotropy or FA) among poor readers. We examined whether 100 hours of intensive remedial instruction affected the white matter of 8–10-year-old poor readers. Prior to instruction, poor readers had significantly lower FA than good readers in a region of the left anterior centrum semiovale. The instruction resulted in a change in white matter (significantly increased FA), and in the very same region. The FA increase was correlated with a decrease in radial diffusivity (but not with a change in axial diffusivity), suggesting that myelination had increased. Furthermore, the FA increase was correlated with improvement in phonological decoding ability, clarifying the cognitive locus of the effect. The results demonstrate for the first time the capability of a behavioral intervention to bring about a positive change in cortico-cortical white matter tracts. PMID:20005820

Sex differences in white matter development during adolescence: a DTI study.

PubMed

Wang, Yingying; Adamson, Chris; Yuan, Weihong; Altaye, Mekibib; Rajagopal, Akila; Byars, Anna W; Holland, Scott K

2012-10-10

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure. Copyright © 2012 Elsevier B.V. All rights reserved.

Superficial white matter damage in anti-NMDA receptor encephalitis.

PubMed

Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

2018-05-01

Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Age-related differences in autism: The case of white matter microstructure.

PubMed

Koolschijn, P Cédric M P; Caan, Matthan W A; Teeuw, Jalmar; Olabarriaga, Sílvia D; Geurts, Hilde M

2017-01-01

Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Diffusion-Weighted Magnetic Resonance Imaging Characterization of White Matter Injury Produced by Axon-Sparing Demyelination and Severe Contusion Spinal Cord Injury in Rats

PubMed Central

Nout-Lomas, Yvette S.; Wendland, Michael F.; Mukherjee, Pratik; Huie, J. Russell; Hess, Christopher P.; Mabray, Marc C.; Bresnahan, Jacqueline C.; Beattie, Michael S.

2016-01-01

Abstract Alterations in magnetic resonance imaging (MRI)–derived measurements of water diffusion parallel (D∥) and perpendicular (D⊥) to white matter tracts have been specifically attributed to pathology of axons and myelin, respectively. We test the hypothesis that directional diffusion measurements can distinguish between axon-sparing chemical demyelination and severe contusion spinal cord white matter injury. Adult rats received either unilateral ethidium bromide (EB) microinjections (chemical demyelination) into the lateral funiculus of the spinal cord at C5 or were subjected to unilateral severe contusion spinal cord injury (SCI). Diffusion MRI metrics in the lateral funiculus were analyzed at early and late time-points following injury and correlated with histology. Early EB-demyelination resulted in a significant elevation in D⊥ and significant reduction in D∥ at the injury epicenter, with histological evidence of uniform axon preservation. Alterations in D⊥ and D∥ at the epicenter of early EB-demyelination were not significantly different from those observed with severe contusion at the epicenter, where histology demonstrated severe combined axonal and myelin injury. Diffusion abnormalities away from the injury epicenter were seen with contusion injury, but not with EB-demyelination. Chronic EB lesions underwent endogenous remyelination with normalization of diffusion metrics, whereas chronic contusion resulted in persistently altered diffusivities. In the early setting, directional diffusion measurements at the injury epicenter associated with chemical demyelination are indistinguishable from those seen with severe contusive SCI, despite dramatic pathologic differences between injury models. Caution is advised in interpretation of diffusion metrics with respect to specific white matter structural alterations. Diffusion analysis should not be limited to the epicenter of focal spinal lesions as alterations marginal to the epicenter are useful for assessing the nature of focal white matter injury. PMID:26483094

High-grade glioma diffusive modeling using statistical tissue information and diffusion tensors extracted from atlases.

PubMed

Roniotis, Alexandros; Manikis, Georgios C; Sakkalis, Vangelis; Zervakis, Michalis E; Karatzanis, Ioannis; Marias, Kostas

2012-03-01

Glioma, especially glioblastoma, is a leading cause of brain cancer fatality involving highly invasive and neoplastic growth. Diffusive models of glioma growth use variations of the diffusion-reaction equation in order to simulate the invasive patterns of glioma cells by approximating the spatiotemporal change of glioma cell concentration. The most advanced diffusive models take into consideration the heterogeneous velocity of glioma in gray and white matter, by using two different discrete diffusion coefficients in these areas. Moreover, by using diffusion tensor imaging (DTI), they simulate the anisotropic migration of glioma cells, which is facilitated along white fibers, assuming diffusion tensors with different diffusion coefficients along each candidate direction of growth. Our study extends this concept by fully exploiting the proportions of white and gray matter extracted by normal brain atlases, rather than discretizing diffusion coefficients. Moreover, the proportions of white and gray matter, as well as the diffusion tensors, are extracted by the respective atlases; thus, no DTI processing is needed. Finally, we applied this novel glioma growth model on real data and the results indicate that prognostication rates can be improved. © 2012 IEEE

in vivo quantification of white matter microstructure for use in aging: A focus on two emerging techniques

PubMed Central

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A.; Dean, Douglas; Little, Deborah; Deoni, Sean C

2013-01-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. While DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. PMID:24080382

Diffusion Tensor Imaging: Application to the Study of the Developing Brain

ERIC Educational Resources Information Center

Cascio, Carissa J.; Gerig, Guido; Piven, Joseph

2007-01-01

Objective: To provide an overview of diffusion tensor imaging (DTI) and its application to the study of white matter in the developing brain in both healthy and clinical samples. Method: The development of DTI and its application to brain imaging of white matter tracts is discussed. Forty-eight studies using DTI to examine diffusion properties of…

Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians.

PubMed

Liu, Ge; Allen, Ben; Lopez, Oscar; Aizenstein, Howard; Boudreau, Robert; Newman, Anne; Yaffe, Kristine; Kritchevsky, Stephen; Launer, Lenore; Satterfield, Suzanne; Simonsick, Eleanor; Rosano, Caterina

2015-01-01

To quantify racial differences in brain structural characteristics in white and black octogenarians, and to examine whether these characteristics contribute to cognition. Cross-sectional study of 283 adults 79-89 years old (59.4% white;42.0% women) with data on gray matter integrity via diffusion tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and diabetes. Participants were recruited from an ongoing epidemiological study of older adults living in the community with a range of chronic conditions, physical and cognitive function. Standardized betas (sβ) of neuroimaging markers predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State Examination (3MS) scores were computed in multivariable regression models stratified by race. Compared to whites, blacks had lower DSST (p=0.001) and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter microstructural integrity, p=0.032), independent of gender, income, literacy, body mass index, diabetes and drinking habits. Racial differences were not significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and WMH were associated with DSST (sβ=-.209, p=0.037 and -.211, p=.038, respectively) independent of each other and other covariates; among whites, mean diffusivity, but not WMH, was significantly associated with DSST and 3MS (sβ =-.277, p=.002 and -.250, p=0.029, respectively). In this cohort of octogenarians living in the community, blacks appeared to have higher microstructural integrity of gray matter as compared to whites. This neuroimaging marker was related to higher cognition even in the presence of WMH and other cardiovascular conditions. If confirmed, these findings suggest microstructural gray matter integrity may be a target to improve cognition, especially among blacks who survive to very old age with a range of chronic cardiovascular conditions.

BDNF Val66Met polymorphism modulates the effect of loneliness on white matter microstructure in young adults.

PubMed

Meng, Jie; Hao, Lei; Wei, Dongtao; Sun, Jiangzhou; Li, Yu; Qiu, Jiang

2017-12-01

Loneliness is a common experience. Susceptibility to loneliness is a stable trait and is heritable. Previous studies have suggested that loneliness may impact regional gray matter density and brain activation to social stimuli, but its relation to white matter structure and how it may interact with genetic factors remains unclear. In this study, we investigated whether and how a common polymorphism (Val66Met) in the brain-derived neurotrophic factor gene modulated the association between loneliness and white matter microstructure in 162 young adults. The tract-based spatial statistics analyses revealed that the relationships between loneliness and white matter microstructures were significantly different between Val/Met heterozygotes and Val/Val homozygotes. Specifically, loneliness was significantly correlated with reduced fractional anisotropy and increased radial diffusivity in widespread white matter fibers within Val/Met heterozygotes. It was also significantly correlated with increased radial diffusivity in Met/Met genotypes but showed no significant association with white matter measures in Val/Val genotypes. Furthermore, the associations between loneliness and fractional anisotropy (or radial diffusivity) in Val/Met heterozygotes turned out to be global effects. These results provide evidence that loneliness may interact with the BDNF Val66Met polymorphism to shape the microstructures of white matter, and the Val/Met heterozygotes may be more susceptible to social environment. Copyright © 2017 Elsevier B.V. All rights reserved.

The white matter query language: a novel approach for describing human white matter anatomy

PubMed Central

Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2016-01-01

We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist’s expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia. PMID:26754839

The white matter query language: a novel approach for describing human white matter anatomy.

PubMed

Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2016-12-01

We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist's expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia.

Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

PubMed Central

Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

2014-01-01

Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

White matter microstructure on diffusion tensor imaging is associated with conventional magnetic resonance imaging findings and cognitive function in adolescents born preterm

PubMed Central

FELDMAN, HEIDI M; LEE, ELIANA S; LOE, IRENE M; YEOM, KRISTEN W; GRILL-SPECTOR, KALANIT; LUNA, BEATRIZ

2013-01-01

AIM Diffusion tensor imaging (DTI) was used to evaluate white matter architecture after preterm birth. The goals were (1) to compare white matter microstructure in two cohorts of preterm- and term-born children; and (2) within preterm groups, to determine if sex, gestational age, birthweight, white matter injury score from conventional magnetic resonance imaging (MRI), or IQ was associated with DTI measures. METHOD Participants (n=121; 66 females, 55 males) were aged 9 to 16 years. They comprised 58 preterm children (site 1, n=25; and site 2, n=33) born at less than 36 weeks’ gestation (mean 29.4wks; birthweight 1289g) and 63 term children (site 1, n=40; site 2, n=23) born at more than 37 weeks’ gestation. DTI was analyzed using tract-based spatial statistics. Diffusion measures were fractional anisotropy, axial, radial, and mean diffusivity. RESULTS In no region of the white matter skeleton was fractional anisotropy lower in the preterm group at either site. Within the preterm groups, fractional anisotropy was significantly associated with white matter injury score, but not sex, gestational age, or birthweight. At site 1, fractional anisotropy was associated with IQ. INTERPRETATION DTI contributes to understanding individual differences after preterm birth but may not differentiate a relatively high-functioning group of preterm children from a matched group of term-born children. PMID:22803787

Profiles of White Matter Tract Pathology in Frontotemporal Dementia

PubMed Central

Mahoney, Colin J; Ridgway, Gerard R; Malone, Ian B; Downey, Laura E; Beck, Jonathan; Kinnunen, Kirsi M; Schmitz, Nicole; Golden, Hannah L; Rohrer, Jonathan D; Schott, Jonathan M; Rossor, Martin N; Ourselin, Sebastien; Mead, Simon; Fox, Nick C; Warren, Jason D

2014-01-01

Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. PMID:24510641

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Diffusion tensor imaging with direct cytopathological validation: characterisation of decorin treatment in experimental juvenile communicating hydrocephalus.

PubMed

Aojula, Anuriti; Botfield, Hannah; McAllister, James Patterson; Gonzalez, Ana Maria; Abdullah, Osama; Logan, Ann; Sinclair, Alexandra

2016-05-31

In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculomegaly; however decorin's ability to prevent cerebral cytopathology in communicating hydrocephalus has not been fully examined. Furthermore, the capacity for diffusion tensor imaging to act as a proxy measure of cerebral pathology in multiple sclerosis and spinal cord injury has recently been demonstrated. However, the use of diffusion tensor imaging to investigate cytopathological changes in communicating hydrocephalus is yet to occur. Hence, this study aimed to determine whether decorin treatment influences alterations in diffusion tensor imaging parameters and cytopathology in experimental communicating hydrocephalus. Moreover, the study also explored whether diffusion tensor imaging parameters correlate with cellular pathology in communicating hydrocephalus. Accordingly, communicating hydrocephalus was induced by injecting kaolin into the basal cisterns in 3-week old rats followed immediately by 14 days of continuous intraventricular delivery of either human recombinant decorin (n = 5) or vehicle (n = 6). Four rats remained as intact controls and a further four rats served as kaolin only controls. At 14-days post-kaolin, just prior to sacrifice, routine magnetic resonance imaging and magnetic resonance diffusion tensor imaging was conducted and the mean diffusivity, fractional anisotropy, radial and axial diffusivity of seven cerebral regions were assessed by voxel-based analysis in the corpus callosum, periventricular white matter, caudal internal capsule, CA1 hippocampus, and outer and inner parietal cortex. Myelin integrity, gliosis and aquaporin-4 levels were evaluated by post-mortem immunohistochemistry in the CA3 hippocampus and in the caudal brain of the same cerebral structures analysed by diffusion tensor imaging. Decorin significantly decreased myelin damage in the caudal internal capsule and prevented caudal periventricular white matter oedema and astrogliosis. Furthermore, decorin treatment prevented the increase in caudal periventricular white matter mean diffusivity (p = 0.032) as well as caudal corpus callosum axial diffusivity (p = 0.004) and radial diffusivity (p = 0.034). Furthermore, diffusion tensor imaging parameters correlated primarily with periventricular white matter astrocyte and aquaporin-4 levels. Overall, these findings suggest that decorin has the therapeutic potential to reduce white matter cytopathology in hydrocephalus. Moreover, diffusion tensor imaging is a useful tool to provide surrogate measures of periventricular white matter pathology in communicating hydrocephalus.

White matter changes and word finding failures with increasing age.

PubMed

Stamatakis, Emmanuel A; Shafto, Meredith A; Williams, Guy; Tam, Phyllis; Tyler, Lorraine K

2011-01-07

Increasing life expectancy necessitates the better understanding of the neurophysiological underpinnings of age-related cognitive changes. The majority of research examining structural-cognitive relationships in aging focuses on the role of age-related changes to grey matter integrity. In the current study, we examined the relationship between age-related changes in white matter and language production. More specifically, we concentrated on word-finding failures, which increase with age. We used Diffusion tensor MRI (a technique used to image, in vivo, the diffusion of water molecules in brain tissue) to relate white matter integrity to measures of successful and unsuccessful picture naming. Diffusion tensor images were used to calculate Fractional Anisotropy (FA) images. FA is considered to be a measure of white matter organization/integrity. FA images were related to measures of successful picture naming and to word finding failures using voxel-based linear regression analyses. Successful naming rates correlated positively with white matter integrity across a broad range of regions implicated in language production. However, word finding failure rates correlated negatively with a more restricted region in the posterior aspect of superior longitudinal fasciculus. The use of DTI-MRI provides evidence for the relationship between age-related white matter changes in specific language regions and word finding failures in old age.

Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

PubMed

Hubbard, Nicholas A; Turner, Monroe P; Ouyang, Minhui; Himes, Lyndahl; Thomas, Binu P; Hutchison, Joanna L; Faghihahmadabadi, Shawheen; Davis, Scott L; Strain, Jeremy F; Spence, Jeffrey; Krawczyk, Daniel C; Huang, Hao; Lu, Hanzhang; Hart, John; Frohman, Teresa C; Frohman, Elliot M; Okuda, Darin T; Rypma, Bart

2017-11-01

Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO 2 ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO 2 . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO 2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

White matter damage in primary progressive aphasias: a diffusion tensor tractography study.

PubMed

Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M; Henry, Maya L; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F; Henry, Roland G; Ogar, Jennifer M; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2011-10-01

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

PubMed Central

Weber, Bernd; Schoene-Bake, Jan-Christoph; Roeske, Sandra; Mirbach, Sandra; Anspach, Christian; Schneider-Gold, Christiane; Betz, Regina C.; Helmstaedter, Christoph; Tittgemeyer, Marc; Klockgether, Thomas; Kornblum, Cornelia

2011-01-01

Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T1/T2/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (Pcorrected < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1 with less white matter affection (early disease stages), contrary to patients with myotonic dystrophy type 2. Thus, depression in myotonic dystrophies might be a reactive adjustment disorder rather than a direct consequence of structural brain damage. Associations of white matter affection with age/disease duration as well as patterns of cerebral water diffusion parameters pointed towards an ongoing process of myelin destruction and/or axonal loss in our cross-sectional study design. Our data suggest that both myotonic dystrophy types 1 and 2 are serious white matter diseases with prominent callosal body and limbic system affection. White matter changes dominated the extent of grey matter changes, which might argue against Wallerian degeneration as the major cause of white matter affection in myotonic dystrophies. PMID:22131273

Combining tract- and atlas-based analysis reveals microstructural abnormalities in early Tourette syndrome children.

PubMed

Wen, Hongwei; Liu, Yue; Wang, Jieqiong; Rekik, Islem; Zhang, Jishui; Zhang, Yue; Tian, Hongwei; Peng, Yun; He, Huiguang

2016-05-01

Tourette syndrome (TS) is a neurological disorder that causes uncontrolled repetitive motor and vocal tics in children. Examining the neural basis of TS churned out different research studies that advanced our understanding of the brain pathways involved in its development. Particularly, growing evidence points to abnormalities within the fronto-striato-thalamic pathways. In this study, we combined Tract-Based Spatial Statistics (TBSS) and Atlas-based regions of interest (ROI) analysis approach, to investigate the microstructural diffusion changes in both deep and superficial white matter (SWM) in TS children. We then characterized the altered microstructure of white matter in 27 TS children in comparison with 27 age- and gender-matched healthy controls. We found that fractional anisotropy (FA) decreases and radial diffusivity (RD) increases in deep white matter (DWM) tracts in cortico-striato-thalamo-cortical (CSTC) circuit as well as SWM. Furthermore, we found that lower FA values and higher RD values in white matter regions are correlated with more severe tics, but not tics duration. Besides, we also found both axial diffusivity and mean diffusivity increase using Atlas-based ROI analysis. Our work may suggest that microstructural diffusion changes in white matter is not only restricted to the gray matter of CSTC circuit but also affects SWM within the primary motor and somatosensory cortex, commissural and association fibers. Hum Brain Mapp 37:1903-1919, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Impact of Sex, Puberty, and Hormones on White Matter Microstructure in Adolescents

PubMed Central

Herting, Megan M.; Maxwell, Emily C.; Irvine, Christy

2012-01-01

Background: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. Methods: White matter microstructure was examined in 77 adolescents (ages 10–16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. Results: Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. Conclusions: Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids. PMID:22002939

The dimensionality of between-person differences in white matter microstructure in old age.

PubMed

Lövdén, Martin; Laukka, Erika Jonsson; Rieckmann, Anna; Kalpouzos, Grégoria; Li, Tie-Qiang; Jonsson, Tomas; Wahlund, Lars-Olof; Fratiglioni, Laura; Bäckman, Lars

2013-06-01

Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60-87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Copyright © 2011 Wiley Periodicals, Inc.

White matter abnormalities of microstructure and physiological noise in schizophrenia.

PubMed

Cheng, Hu; Newman, Sharlene D; Kent, Jerillyn S; Bolbecker, Amanda; Klaunig, Mallory J; O'Donnell, Brian F; Puce, Aina; Hetrick, William P

2015-12-01

White matter abnormalities in schizophrenia have been revealed by many imaging techniques and analysis methods. One of the findings by diffusion tensor imaging is a decrease in fractional anisotropy (FA), which is an indicator of white matter integrity. On the other hand, elevation of metabolic rate in white matter was observed from positron emission tomography (PET) studies. In this report, we aim to compare the two structural and functional effects on the same subjects. Our comparison is based on the hypothesis that signal fluctuation in white matter is associated with white matter functional activity. We examined the variance of the signal in resting state fMRI and found significant differences between individuals with schizophrenia and non-psychiatric controls specifically in white matter tissue. Controls showed higher temporal signal-to-noise ratios clustered in regions including temporal, frontal, and parietal lobes, cerebellum, corpus callosum, superior longitudinal fasciculus, and other major white matter tracts. These regions with higher temporal signal-to-noise ratio agree well with those showing higher metabolic activity reported by studies using PET. The results suggest that individuals with schizophrenia tend to have higher functional activity in white matter in certain brain regions relative to healthy controls. Despite some overlaps, the distinct regions for physiological noise are different from those for FA derived from diffusion tensor imaging, and therefore provide a unique angle to explore potential mechanisms to white matter abnormality.

In vivo quantification of white matter microstructure for use in aging: a focus on two emerging techniques.

PubMed

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A; Dean, Douglas; Little, Deborah; Deoni, Sean C

2014-02-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. Although DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

PubMed

Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

2012-01-16

Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Disrupted white matter integrity in heroin dependence: a controlled study utilizing diffusion tensor imaging.

PubMed

Liu, Haihong; Li, Lin; Hao, Yihui; Cao, Dong; Xu, Lin; Rohrbaugh, Robert; Xue, Zhimin; Hao, Wei; Shan, Baoci; Liu, Zhening

2008-01-01

Fractional anisotropy (FA) via diffusion tensor imaging (DTI) can quantify the white matter integrity. Exposure to addictive drugs, such as alcohol, cocaine, methamphetamine, marijuana, and nicotine has been shown to alter FA. White matter abnormalities have been shown, but it remains unclear whether the white matter FA is altered in heroin dependence. Utilizing DTI, we investigated the FA difference between heroin-dependent and control subjects by a voxel-based strategy. The FA values of the identified regions were calculated from the FA image of each subject and were correlated with clinical features including months of heroin use, age, education, and dose of methadone. Reduced FA among 16 heroin dependent subjects was located in the bilateral frontal sub-gyral regions, right precentral and left cingulate gyrus. FA in the right frontal sub-gyral was negatively correlated with duration of heroin use. The disrupted white matter integrity in right frontal white matter may occur in continuous heroin abuse.

Monotonic non-linear transformations as a tool to investigate age-related effects on brain white matter integrity: A Box-Cox investigation.

PubMed

Morozova, Maria; Koschutnig, Karl; Klein, Elise; Wood, Guilherme

2016-01-15

Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box-Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box-Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89years of age (n=88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box-Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box-Cox analysis in neuroimaging. Copyright © 2015 Elsevier Inc. All rights reserved.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

PubMed

Luo, ChunYan; Song, Wei; Chen, Qin; Yang, Jing; Gong, QiYong; Shang, Hui-Fang

2017-07-01

Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

White Matter Microstructure in Transsexuals and Controls Investigated by Diffusion Tensor Imaging

PubMed Central

Kranz, Georg S.; Hahn, Andreas; Kaufmann, Ulrike; Küblböck, Martin; Hummer, Allan; Ganger, Sebastian; Seiger, Rene; Winkler, Dietmar; Swaab, Dick F.; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

2015-01-01

Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects’ sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. PMID:25392513

Modeling fluid diffusion in cerebral white matter with random walks in complex environments

NASA Astrophysics Data System (ADS)

Levy, Amichai; Cwilich, Gabriel; Buldyrev, Sergey V.; Weeden, Van J.

2012-02-01

Recent studies with diffusion MRI have shown new aspects of geometric order in the brain, including complex path coherence within the cerebral cortex, and organization of cerebral white matter and connectivity across multiple scales. The main assumption of these studies is that water molecules diffuse along myelin sheaths of neuron axons in the white matter and thus the anisotropy of their diffusion tensor observed by MRI can provide information about the direction of the axons connecting different parts of the brain. We model the diffusion of particles confined in the space of between the bundles of cylindrical obstacles representing fibrous structures of various orientations. We have investigated the directional properties of the diffusion, by studying the angular distribution of the end point of the random walks as a function of their length, to understand the scale over which the distribution randomizes. We will show evidence of qualitative change in the behavior of the diffusion for different volume fractions of obstacles. Comparisons with three-dimensional MRI images will be illustrated.

Fiber tracking of brain white matter based on graph theory.

PubMed

Lu, Meng

2015-01-01

Brain white matter tractography is reconstructed via diffusion-weighted magnetic resonance images. Due to the complex structure of brain white matter fiber bundles, fiber crossing and fiber branching are abundant in human brain. And regular methods with diffusion tensor imaging (DTI) can't accurately handle this problem. the biggest problems of the brain tractography. Therefore, this paper presented a novel brain white matter tractography method based on graph theory, so the fiber tracking between two voxels is transformed into locating the shortest path in a graph. Besides, the presented method uses Q-ball imaging (QBI) as the source data instead of DTI, because QBI can provide accurate information about multiple fiber crossing and branching in one voxel using orientation distribution function (ODF). Experiments showed that the presented method can accurately handle the problem of brain white matter fiber crossing and branching, and reconstruct brain tractograhpy both in phantom data and real brain data.

Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy.

PubMed

Holleran, Laurena; Kim, Joong Hee; Gangolli, Mihika; Stein, Thor; Alvarez, Victor; McKee, Ann; Brody, David L

2017-03-01

Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm 3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

PubMed

Witwer, Brian P; Moftakhar, Roham; Hasan, Khader M; Deshmukh, Praveen; Haughton, Victor; Field, Aaron; Arfanakis, Konstantinos; Noyes, Jane; Moritz, Chad H; Meyerand, M Elizabeth; Rowley, Howard A; Alexander, Andrew L; Badie, Behnam

2002-09-01

Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

White Matter Integrity and Pictorial Reasoning in High-Functioning Children with Autism

ERIC Educational Resources Information Center

Sahyoun, Cherif P.; Belliveau, John W.; Mody, Maria

2010-01-01

The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups' response…

Microstructural Abnormalities of Short-Distance White Matter Tracts in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Smylie, Daren M.; Muller, Ralph-Axel

2011-01-01

Recent functional connectivity magnetic resonance imaging and diffusion tensor imaging (DTI) studies have suggested atypical functional connectivity and reduced integrity of long-distance white matter fibers in autism spectrum disorder (ASD). However, evidence for short-distance white matter fibers is still limited, despite some speculation of…

Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis.

PubMed

Barnea-Goraly, Naama; Chang, Kiki D; Karchemskiy, Asya; Howe, Meghan E; Reiss, Allan L

2009-08-01

Bipolar disorder (BD) is a common and debilitating condition, often beginning in adolescence. Converging evidence from genetic and neuroimaging studies indicates that white matter abnormalities may be involved in BD. In this study, we investigated white matter structure in adolescents with familial bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis. We analyzed DTI images using tract-based spatial statistics (TBSS), a whole-brain voxel-by-voxel analysis, to investigate white matter structure in 21 adolescents with BD, who also were offspring of at least one parent with BD, and 18 age- and IQ-matched control subjects. Fractional anisotropy (FA; a measure of diffusion anisotropy), trace values (average diffusivity), and apparent diffusion coefficient (ADC; a measure of overall diffusivity) were used as variables in this analysis. In a post hoc analysis, we correlated between FA values, behavioral measures, and medication exposure. Adolescents with BD had lower FA values than control subjects in the fornix, the left mid-posterior cingulate gyrus, throughout the corpus callosum, in fibers extending from the fornix to the thalamus, and in parietal and occipital corona radiata bilaterally. There were no significant between-group differences in trace or ADC values and no significant correlation between behavioral measures, medication exposure, and FA values. Significant white matter tract alterations in adolescents with BD were observed in regions involved in emotional, behavioral, and cognitive regulation. These results suggest that alterations in white matter are present early in the course of disease in familial BD.

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

PubMed

Zhang, Xiaodong; Yan, Yumei; Tong, Frank; Li, Chun-Xia; Jones, Benjamin; Wang, Silun; Meng, Yuguang; Muly, E Chris; Kempf, Doty; Howell, Leonard

2018-01-01

Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings. The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

Numerical simulation model of hyperacute/acute stage white matter infarction.

PubMed

Sakai, Koji; Yamada, Kei; Oouchi, Hiroyuki; Nishimura, Tsunehiko

2008-01-01

Although previous studies have revealed the mechanisms of changes in diffusivity (apparent diffusion coefficient [ADC]) in acute brain infarction, changes in diffusion anisotropy (fractional anisotropy [FA]) in white matter have not been examined. We hypothesized that membrane permeability as well as axonal swelling play important roles, and we therefore constructed a simulation model using random walk simulation to replicate the diffusion of water molecules. We implemented a numerical diffusion simulation model of normal and infarcted human brains using C++ language. We constructed this 2-pool model using simple tubes aligned in a single direction. Random walk simulation diffused water. Axon diameters and membrane permeability were then altered in step-wise fashion. To estimate the effects of axonal swelling, axon diameters were changed from 6 to 10 microm. Membrane permeability was altered from 0% to 40%. Finally, both elements were combined to explain increasing FA in the hyperacute stage of white matter infarction. The simulation demonstrated that simple water shift into the intracellular space reduces ADC and increases FA, but not to the extent expected from actual human cases (ADC approximately 50%; FA approximately +20%). Similarly, membrane permeability alone was insufficient to explain this phenomenon. However, a combination of both factors successfully replicated changes in diffusivity indices. Both axonal swelling and reduced membrane permeability appear important in explaining changes in ADC and FA based on eigenvalues in hyperacute-stage white matter infarction.

Mapping White Matter Microstructure in the One Month Human Brain.

PubMed

Dean, D C; Planalp, E M; Wooten, W; Adluru, N; Kecskemeti, S R; Frye, C; Schmidt, C K; Schmidt, N L; Styner, M A; Goldsmith, H H; Davidson, R J; Alexander, A L

2017-08-29

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Selective white matter pathology induces a specific impairment in spatial working memory.

PubMed

Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen

2011-12-01

The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing parallel pathology and behavior in the same mice. Copyright © 2011. Published by Elsevier Inc.

Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

PubMed

Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

2013-01-01

It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging

PubMed Central

Ly, Martina; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Zetterberg, Henrik; Blennow, Kaj; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2017-01-01

Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI. PMID:28291839

White matter damage in primary progressive aphasias: a diffusion tensor tractography study

PubMed Central

Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M.; Henry, Maya L.; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F.; Henry, Roland G.; Ogar, Jennifer M.; Miller, Bruce L.

2011-01-01

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts’ mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia. PMID:21666264

Structural white matter changes in adolescents and young adults with maple syrup urine disease.

PubMed

Klee, D; Thimm, E; Wittsack, H J; Schubert, D; Primke, R; Pentang, G; Schaper, J; Mödder, U; Antoch, A; Wendel, U; Cohnen, M

2013-11-01

To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.

Microstructural white matter tract alteration in Prader-Willi syndrome: A diffusion tensor imaging study.

PubMed

Rice, Lauren J; Lagopoulos, Jim; Brammer, Michael; Einfeld, Stewart L

2017-09-01

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by infantile hypotonia, hyperphagia, hypogonadism, growth hormone deficiency, intellectual disability, and severe emotional and behavioral problems. The brain mechanisms that underpin these disturbances are unknown. Diffusion tensor imaging (DTI) enables in vivo investigation of the microstructural integrity of white matter pathways. To date, only one study has used DTI to examine white matter alterations in PWS. However, that study used selected regions of interest, rather than a whole brain analysis. In the present study, we used diffusion tensor and magnetic resonance (T 1-weighted) imaging to examine microstructural white matter changes in 15 individuals with PWS (17-30 years) and 15 age-and-gender-matched controls. Whole-brain voxel-wise statistical analysis of FA was carried out using tract-based spatial statistics (TBSS). Significantly decreased fractional anisotropy was found localized to the left hemisphere in individuals with PWS within the splenium of the corpus callosum, the internal capsule including the posterior thalamic radiation and the inferior frontal occipital fasciculus (IFOF). Reduced integrity of these white matter pathways in individuals with PWS may relate to orientating attention, emotion recognition, semantic processing, and sensorimotor dysfunction. © 2017 Wiley Periodicals, Inc.

White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging.

PubMed

Kranz, Georg S; Hahn, Andreas; Kaufmann, Ulrike; Küblböck, Martin; Hummer, Allan; Ganger, Sebastian; Seiger, Rene; Winkler, Dietmar; Swaab, Dick F; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

2014-11-12

Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. Copyright © 2014 the authors 0270-6474/14/3415466-10$15.00/0.

A Modified Tri-Exponential Model for Multi-b-value Diffusion-Weighted Imaging: A Method to Detect the Strictly Diffusion-Limited Compartment in Brain

PubMed Central

Zeng, Qiang; Shi, Feina; Zhang, Jianmin; Ling, Chenhan; Dong, Fei; Jiang, Biao

2018-01-01

Purpose: To present a new modified tri-exponential model for diffusion-weighted imaging (DWI) to detect the strictly diffusion-limited compartment, and to compare it with the conventional bi- and tri-exponential models. Methods: Multi-b-value diffusion-weighted imaging (DWI) with 17 b-values up to 8,000 s/mm2 were performed on six volunteers. The corrected Akaike information criterions (AICc) and squared predicted errors (SPE) were calculated to compare these three models. Results: The mean f0 values were ranging 11.9–18.7% in white matter ROIs and 1.2–2.7% in gray matter ROIs. In all white matter ROIs: the AICcs of the modified tri-exponential model were the lowest (p < 0.05 for five ROIs), indicating the new model has the best fit among these models; the SPEs of the bi-exponential model were the highest (p < 0.05), suggesting the bi-exponential model is unable to predict the signal intensity at ultra-high b-value. The mean ADCvery−slow values were extremely low in white matter (1–7 × 10−6 mm2/s), but not in gray matter (251–445 × 10−6 mm2/s), indicating that the conventional tri-exponential model fails to represent a special compartment. Conclusions: The strictly diffusion-limited compartment may be an important component in white matter. The new model fits better than the other two models, and may provide additional information. PMID:29535599

Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.

PubMed

Gong, Nan-Jie; Wong, Chun-Sing; Chan, Chun-Chung; Leung, Lam-Ming; Chu, Yiu-Ching

2014-10-01

Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

Three-year changes in leisure activities are associated with concurrent changes in white matter microstructure and perceptual speed in individuals aged 80 years and older.

PubMed

Köhncke, Ylva; Laukka, Erika J; Brehmer, Yvonne; Kalpouzos, Grégoria; Li, Tie-Qiang; Fratiglioni, Laura; Bäckman, Lars; Lövdén, Martin

2016-05-01

Accumulating evidence suggests that engagement in leisure activities is associated with favorable trajectories of cognitive aging, but little is known about brain changes related to both activities and cognition. White matter microstructure shows experience-dependent plasticity and declines in aging. Therefore, we investigated the role of change in white matter microstructure in the activities-cognition link. We used repeated assessments of engagement, perceptual speed, and white matter microstructure (probed with diffusion tensor imaging) in a population-based sample of individuals over 80 years without dementia (n = 442, Mage = 85.1; n = 70 for diffusion tensor imaging; 2 occasions 3 years apart). Using multivariate latent change modeling, we observed positive correlations among changes in predominantly social activities, white matter microstructure, and perceptual speed. Interindividual differences in change in white matter microstructure statistically accounted for the association between change in leisure activities and change in perceptual speed. However, as analyses are based on observational data from 2 measurement occasions, causality remains unclear. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative analysis of diffusion tensor orientation: theoretical framework.

PubMed

Wu, Yu-Chien; Field, Aaron S; Chung, Moo K; Badie, Benham; Alexander, Andrew L

2004-11-01

Diffusion-tensor MRI (DT-MRI) yields information about the magnitude, anisotropy, and orientation of water diffusion of brain tissues. Although white matter tractography and eigenvector color maps provide visually appealing displays of white matter tract organization, they do not easily lend themselves to quantitative and statistical analysis. In this study, a set of visual and quantitative tools for the investigation of tensor orientations in the human brain was developed. Visual tools included rose diagrams, which are spherical coordinate histograms of the major eigenvector directions, and 3D scatterplots of the major eigenvector angles. A scatter matrix of major eigenvector directions was used to describe the distribution of major eigenvectors in a defined anatomic region. A measure of eigenvector dispersion was developed to describe the degree of eigenvector coherence in the selected region. These tools were used to evaluate directional organization and the interhemispheric symmetry of DT-MRI data in five healthy human brains and two patients with infiltrative diseases of the white matter tracts. In normal anatomical white matter tracts, a high degree of directional coherence and interhemispheric symmetry was observed. The infiltrative diseases appeared to alter the eigenvector properties of affected white matter tracts, showing decreased eigenvector coherence and interhemispheric symmetry. This novel approach distills the rich, 3D information available from the diffusion tensor into a form that lends itself to quantitative analysis and statistical hypothesis testing. (c) 2004 Wiley-Liss, Inc.

Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants.

PubMed

Anjari, Mustafa; Srinivasan, Latha; Allsop, Joanna M; Hajnal, Joseph V; Rutherford, Mary A; Edwards, A David; Counsell, Serena J

2007-04-15

Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions.

Tract-Specific Analyses of Diffusion Tensor Imaging Show Widespread White Matter Compromise in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Muller, Ralph-Axel

2011-01-01

Background: Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS)…

Local White Matter Geometry from Diffusion Tensor Gradients

PubMed Central

Savadjiev, Peter; Kindlmann, Gordon L.; Bouix, Sylvain; Shenton, Martha E.; Westin, Carl-Fredrik

2009-01-01

We introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia. PMID:19896542

Local White Matter Geometry from Diffusion Tensor Gradients

PubMed Central

Savadjiev, Peter; Kindlmann, Gordon L.; Bouix, Sylvain; Shenton, Martha E.; Westin, Carl-Fredrik

2010-01-01

We introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia. PMID:20426006

Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

PubMed

Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

2018-01-15

To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Prepartum and Postpartum Maternal Depressive Symptoms Are Related to Children's Brain Structure in Preschool.

PubMed

Lebel, Catherine; Walton, Matthew; Letourneau, Nicole; Giesbrecht, Gerald F; Kaplan, Bonnie J; Dewey, Deborah

2016-12-01

Perinatal maternal depression is a serious health concern with potential lasting negative consequences for children. Prenatal depression is associated with altered brain gray matter in children, though relations between postpartum depression and children's brains and the role of white matter are unclear. We studied 52 women who provided Edinburgh Postnatal Depression Scale (EPDS) scores during each trimester of pregnancy and at 3 months postpartum and their children who underwent magnetic resonance imaging at age 2.6 to 5.1 years. Associations between maternal depressive symptoms and magnetic resonance imaging measures of cortical thickness and white matter structure in the children were investigated. Women's second trimester EPDS scores negatively correlated with children's cortical thickness in right inferior frontal and middle temporal regions and with radial and mean diffusivity in white matter emanating from the inferior frontal area. Cortical thickness, but not diffusivity, correlations survived correction for postpartum EPDS. Postpartum EPDS scores negatively correlated with children's right superior frontal cortical thickness and with diffusivity in white matter originating from that region, even after correcting for prenatal EPDS. Higher maternal depressive symptoms prenatally and postpartum are associated with altered gray matter structure in children; the observed white matter correlations appear to be uniquely related to the postpartum period. The reduced thickness and diffusivity suggest premature brain development in children exposed to higher maternal perinatal depressive symptoms. These results highlight the importance of ensuring optimal women's mental health throughout the perinatal period, because maternal depressive symptoms appear to increase children's vulnerability to nonoptimal brain development. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Diffusion-weighted MR of the brain: methodology and clinical application.

PubMed

Mascalchi, Mario; Filippi, Massimo; Floris, Roberto; Fonda, Claudio; Gasparotti, Roberto; Villari, Natale

2005-03-01

Clinical diffusion magnetic resonance (MR) imaging in humans started in the last decade with the demonstration of the capabilities of this technique of depicting the anatomy of the white matter fibre tracts in the brain. Two main approaches in terms of reconstruction and evaluation of the images obtained with application of diffusion sensitising gradients to an echo planar imaging sequence are possible. The first approach consists of reconstruction of images in which the effect of white matter anisotropy is averaged -- known as the isotropic or diffusion weighted images, which are usually evaluated subjectively for possible areas of increased or decreased signal, reflecting restricted and facilitated diffusion, respectively. The second approach implies reconstruction of image maps of the apparent diffusion coefficient (ADC), in which the T2 weighting of the echo planar diffusion sequence is cancelled out, and their objective, i.e. numerical, evaluation with regions of interest or histogram analysis. This second approach enables a quantitative and reproducible assessment of the diffusion changes not only in areas exhibiting signal abnormality in conventional MR images but also in areas of normal signal. A further level of image post-processing requires the acquisition of images after application of sensitising gradients along at least 6 different spatial orientations and consists of computation of the diffusion tensor and reconstruction of maps of the mean diffusivity (D) and of the white matter anisotropic properties, usually in terms of fractional anisotropy (FA). Diffusion-weighted imaging is complementary to conventional MR imaging in the evaluation of the acute ischaemic stroke. The combination of diffusion and perfusion MR imaging has the potential of providing all the information necessary for the diagnosis and management of the individual patient with acute ischaemic stroke. Diffusion-weighted MR, in particular quantitative evaluation based on the diffusion tensor, has a fundamental role in the assessment of brain maturation and of white matter diseases in the fetus, in the neonate and in the child. Diffusion MR imaging enables a better characterisation of the lesions demonstrated by conventional MR imaging, for instance in the hypoxic-ischaemic encephalopathy, in infections and in the inherited metabolic diseases, and is particularly important for the longitudinal evaluation of these conditions. Diffusion-weighted MR imaging has an established role in the differential diagnosis between brain abscess and cystic tumour and between epidermoid tumour and arachnoid cyst. On the other hand, the results obtained with diffusion MR in the characterisation of type and extension of glioma do not yet allow decision making in the individual patient. Diffusion is one of the most relevant MR techniques to have contributed to a better understanding of the pathophysiological mechanisms of multiple sclerosis (MS). In fact, it improves the specificity of MR in characterising the different pathological substrata underlying the rather uniform lesion appearance on the conventional images and enables detection of damage in the normal-appearing white and grey matter. In MS patients the ADC or D values in the normal-appearing white matter are increased as compared to control values, albeit to a lesser degree than in the lesions demonstrated by T2-weighted images. In addition, the D of the normal appearing grey matter is increased in MS patients and this change correlates with the cognitive deficit of these patients. Histogram analysis in MS patients shows that the peak of the brain D is decreased and right-shifted, reflecting an increase of its value, and the two features correlate with the patient's clinical disability. Ageing is associated to a mild but significant increase of the brain ADC or D which is predominantly due to changes in the white matter. Region of interest and histogram studies have demonstrated that D or ADC are increased in either the areas of leukoaraiosis or the normal-appearing white matter in patients with inherited cerebral autosomal dominant arteriopathy with subcortical infarcts and stroke or sporadic ischaemic leukoencephalopathy. Diffusion changes might be a more sensitive marker for progression of the disease than conventional imaging findings. In neurodegenerative diseases of the central nervous system such as Alzheimer's disease, Huntington's disease, hereditary ataxias and motor neuron disease, quantitative diffusion MR demonstrates the cortical and subcortical grey matter damage, which is reflected in a regional increase of D or ADC, but also reveals the concomitant white matter changes that are associated with an increase in D or ADC and decrease in FA. In all these diseases the diffusion changes are correlated to the clinical deficit and are potentially useful for early diagnosis and longitudinal evaluation, especially in the context of pharmacological trials.

White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

PubMed

Uhlmann, Anne; Fouche, Jean-Paul; Lederer, Katharina; Meintjes, Ernesta M; Wilson, Don; Stein, Dan J

2016-06-01

Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Motor skill learning is associated with diffusion characteristics of white matter in individuals with chronic stroke.

PubMed

Borich, Michael R; Brown, Katlyn E; Boyd, Lara A

2014-07-01

Imaging advances allow investigation of white matter after stroke; a growing body of literature has shown links between diffusion-based measures of white matter microstructure and motor function. However, the relationship between these measures and motor skill learning has not been considered in individuals with stroke. The aim of this study was to investigate the relationships between posttraining white matter microstructural status, as indexed by diffusion tensor imaging within the ipsilesional posterior limb of the internal capsule (PLIC), and learning of a novel motor task in individuals with chronic stroke. A total of 13 participants with chronic stroke and 9 healthy controls practiced a visuomotor pursuit task across 5 sessions. Change in motor behavior associated with learning was indexed by comparing baseline performance with a delayed retention test. Fractional anisotropy (FA) indexed at the retention test was the primary diffusion tensor imaging-derived outcome measure. In individuals with chronic stroke, we discovered an association between posttraining ipsilesional PLIC FA and the magnitude of change associated with motor learning; hierarchical multiple linear regression analyses revealed that the combination of age, time poststroke, and ipsilesional PLIC FA posttraining was associated with motor learning-related change (R = 0.649; P = 0.02). Baseline motor performance was not related to posttraining ipsilesional PLIC FA. Diffusion characteristics of posttraining ipsilesional PLIC were linked to the magnitude of change in skilled motor behavior. These results imply that the microstructural properties of regional white matter indexed by diffusion behavior may be an important factor to consider when determining potential response to rehabilitation in persons with stroke. (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A59) for more insights from the authors.

Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm.

PubMed

Young, Julia M; Morgan, Benjamin R; Whyte, Hilary E A; Lee, Wayne; Smith, Mary Lou; Raybaud, Charles; Shroff, Manohar M; Sled, John G; Taylor, Margot J

2017-08-01

Identifying trajectories of early white matter development is important for understanding atypical brain development and impaired functional outcomes in children born very preterm (<32 weeks gestational age [GA]). In this study, 161 diffusion images were acquired in children born very preterm (median GA: 29 weeks) shortly following birth (75), term-equivalent (39), 2 years (18), and 4 years of age (29). Diffusion tensors were computed to obtain measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), which were aligned and averaged. A paediatric atlas was applied to obtain diffusion metrics within 12 white matter tracts. Developmental trajectories across time points demonstrated age-related changes which plateaued between term-equivalent and 2 years of age in the majority of posterior tracts and between 2 and 4 years of age in anterior tracts. Between preterm and term-equivalent scans, FA rates of change were slower in anterior than posterior tracts. Partial least squares analyses revealed associations between slower MD and RD rates of change within the external and internal capsule with lower intelligence quotients and language scores at 4 years of age. These results uniquely demonstrate early white matter development and its linkage to cognitive functions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

White Matter Integrity and Pictorial Reasoning in High-Functioning Children with Autism

PubMed Central

Sahyoun, Chérif P.; Belliveau, John W.; Mody, Maria

2010-01-01

The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups’ response times (RT) on a pictorial reasoning task under three conditions: visuospatial, V, semantic, S, and V+S, a hybrid condition allowing language use to facilitate visuospatial transformations. Diffusion-weighted images were collected from HFA and CTRL participants, matched on age and IQ, and significance maps were computed for group differences in fractional anisotropy (FA) and in RT-FA association for each condition. Typically developing children showed increased FA within frontal white matter and the superior longitudinal fasciculus (SLF). HFA showed increased FA within peripheral white matter, including the ventral temporal lobe. Additionally, RT-FA relationships in the semantic condition (S) implicated white matter near the STG and in the SLF within the temporal and frontal lobes to a greater extent in CTRL. Performance in visuospatial reasoning (V, V+S), in comparison, was related to peripheral parietal and superior precentral white matter in HFA, but to the SLF, callosal, and frontal white matter in CTRL. Our results appear to support a preferential use of linguistically-mediated pathways in reasoning by typically-developing children, whereas autistic cognition may rely more on visuospatial processing networks. PMID:20542370

Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

PubMed

Loh, K B; Ramli, N; Tan, L K; Roziah, M; Rahmat, K; Ariffin, H

2012-07-01

The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

PubMed

Padilla, Nelly; Junqué, Carme; Figueras, Francesc; Sanz-Cortes, Magdalena; Bargalló, Núria; Arranz, Angela; Donaire, Antonio; Figueras, Josep; Gratacos, Eduard

2014-01-30

Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined. Copyright © 2013 Elsevier B.V. All rights reserved.

Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Versace, Amelia; Ladouceur, Cecile D.; Romero, Soledad; Birmaher, Boris; Axelson, David A.; Kupfer, David J.; Phillips, Mary L.

2010-01-01

Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy…

Thalamic diffusion differences related to cognitive function in white matter lesions.

PubMed

Fernández-Andújar, Marina; Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Cáceres, Cynthia; Bargalló, Núria; Barrios, Maite; Arenillas, Juan Francisco; Toran, Pere; Alzamora, Maite; Clemente, Imma; Dávalos, Antoni; Mataró, Maria

2014-05-01

Cerebral white matter lesions (WMLs) are related to cognitive deficits, probably due to a disruption of frontal-subcortical circuits. We explored thalamic diffusion differences related to white matter lesions (WMLs) and their association with cognitive function in middle-aged individuals. Ninety-six participants from the Barcelona-AsIA Neuropsychology Study were included. Participants were classified into groups based on low grade and high grade of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). Tract-Based Spatial Statistics was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) values in significant areas were calculated for each subject and correlated with cognitive performance. Participants with high-grade PVHs and DWMHs showed lower FA thalamic values compared to those with low-grade PVHs and DWMHs, respectively. Decreased FA thalamic values in high-grade DWMHs, but not high-grade PVH, were related to lower levels of performance in psychomotor speed, verbal fluency, and visuospatial skills. Thalamic diffusion differences are related to lower cognitive function only in participants with high-grade DWMHs. These results support the hypothesis that fronto-subcortical disruption is associated with cognitive function only in DWMHs. Copyright © 2014 Elsevier Inc. All rights reserved.

Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex.

PubMed

Berns, Gregory S; Moore, Sara; Capra, C Monica

2009-08-26

Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60). The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

Ageing and brain white matter structure in 3,513 UK Biobank participants

PubMed Central

Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

2016-01-01

Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium.

PubMed

Mustafi, Sourajit Mitra; Harezlak, Jaroslaw; Koch, Kevin M; Nencka, Andrew S; Meier, Timothy; West, John D; Giza, Christopher C; DiFiori, John; Guskiewicz, Kevin K; Mihalik, Jason; LaConte, Stephen M; Duma, Stefan M; Broglio, Steven P; Saykin, Andrew J; McCrea, Michael; McAllister, Thomas; Wu, Yu-Chien

2017-10-25

Sport-related concussion (SRC) is an important public health issue. While standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white-matter alterations in football players within 48 hours after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion, and 28 matched controls received clinical assessments and underwent advanced MRI scans. To avoid selection bias and partial voluming effects, whole-brain skeletonized white matter was examined via tract-based spatial statistics (TBSS) to investigate between group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in the brain white matter of the concussed athletes, particularly in frontal and sub-frontal long white-matter tracts. While no DTI metric was associated to any clinical measure in the contact-sport controls, in the concussed group, DTI exhibited correlations with clinical measures. Axial diffusivity demonstrated a significant positive correlation with the Brief Symptom Inventory (BSI) and a trend for a positive correlation with the symptom severity score of the Sports Concussion Assessment Tool (SCAT). In addition, concussed athletes with higher fractional anisotropy performed worse on the cognitive component of the Standardized Assessment of Concussion (SAC). Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white-matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments.

White Matter Microstructure Correlates of Narrative Production in Typically Developing Children and Children with High Functioning Autism

PubMed Central

Mills, Brian; Lai, Janie; Brown, Timothy T.; Erhart, Matthew; Halgren, Eric; Reilly, Judy; Dale, Anders; Appelbaum, Mark; Moses, Pamela

2013-01-01

This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and instead rely on alternative ventral pathways that possibly mediate visual elements of language. PMID:23810972

White matter microstructure in a genetically defined group at increased risk of autism symptoms, and a comparison with idiopathic autism: an exploratory study.

PubMed

Goddard, Marcia N; van Rijn, Sophie; Rombouts, Serge A R B; Swaab, Hanna

2016-12-01

Klinefelter syndrome (47,XXY) is associated with physical, behavioral, and cognitive consequences. Deviations in brain structure and function have been reported, but structural characteristics of white matter have barely been assessed. This exploratory diffusion tensor imaging study assessed white matter microstructure in boys with 47,XXY compared with non-clinical, male controls. Additionally, both similarities and differences between 47,XXY and autism spectrum disorders (ASD) have been reported in cognition, behavior and neural architecture. To further investigate these brain-behavior pathways, white matter microstructure in boys with 47,XXY was compared to that of boys with ASD. Fractional anisotropy (FA), radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) were assessed in 47,XXY (n = 9), ASD (n = 18), and controls (n = 14), using tract-based spatial statistics. Compared with controls, boys with 47,XXY have reduced FA, coupled with reduced Da, in the corpus callosum. Boys with 47,XXY also have reduced Dr. in the left anterior corona radiata and sagittal striatum compared with controls. Compared with boys with ASD, boys with 47,XXY show reduced Da in the right inferior fronto-occipital fasciculus. Although this study is preliminary considering the small sample size, reduced white matter integrity in the corpus callosum may be a contributing factor in the cognitive and behavioral problems associated with 47,XXY. In addition, the differences in white matter microstructure between 47,XXY and ASD may be important for our understanding of the mechanisms that are fundamental to behavioral outcome in social dysfunction, and may be targeted through intervention.

Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes.

PubMed

Nouwen, Arie; Chambers, Alison; Chechlacz, Magdalena; Higgs, Suzanne; Blissett, Jacqueline; Barrett, Timothy G; Allen, Harriet A

2017-01-01

In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities.

Sleep Duration and White Matter Quality in Middle-Aged Adults

PubMed Central

Yaffe, Kristine; Nasrallah, Ilya; Hoang, Tina D.; Lauderdale, Diane S.; Knutson, Kristen L.; Carnethon, Mercedes R.; Launer, Lenore J.; Lewis, Cora E.; Sidney, Stephen

2016-01-01

Study Objectives: Sleep duration has been associated with risk of dementia and stroke, but few studies have investigated the relationship between sleep duration and brain MRI measures, particularly in middle age. Methods: In a prospective cohort of 613 black and white adults (mean age = 45.4 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, participants reported typical sleep duration, dichotomized into moderate sleep duration (> 6 to ≤ 8 h) and short sleep duration (≤ 6 h) at baseline (2005–2006). Five years later, we obtained brain MRI markers of white matter including fractional anisotropy, mean diffusivity, and white matter hyperintensities. Results: Compared to moderate sleepers, short sleepers had an elevated ratio of white matter hyperintensities to normal tissue in the parietal region (OR = 2.31, 95% CI: 1.47, 3.61) adjusted for age, race/sex, education, hypertension, stroke/TIA, depression, smoking status, and physical activity. White matter diffusivity was also higher, approximately a 0.2 standard deviation difference, in frontal, parietal, and temporal white matter regions, among those reporting shorter sleep duration in (P < 0.05 for all). Conclusions: Short sleep duration was associated with worse markers of white matter integrity in midlife. These mid-life differences in white matter may underlie the link between poor sleep and risk of dementia and stroke. Citation: Yaffe K, Nasrallah I, Hoang TD, Lauderdale DS, Knutson KL, Carnethon MR, Launer LJ, Lewis CE, Sidney S. Sleep duration and white matter quality in middle-aged adults. SLEEP 2016;39(9):1743–1747. PMID:27397561

Evaluation of diffusion kurtosis imaging in ex vivo hypomyelinated mouse brains.

PubMed

Kelm, Nathaniel D; West, Kathryn L; Carson, Robert P; Gochberg, Daniel F; Ess, Kevin C; Does, Mark D

2016-01-01

Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and DKI-derived white matter tract integrity metrics (WMTI) were experimentally evaluated ex vivo through comparisons to histological measurements and established magnetic resonance imaging (MRI) measures of myelin in two knockout mouse models with varying degrees of hypomyelination. DKI metrics of mean and radial kurtosis were found to be better indicators of myelin content than conventional DTI metrics. The biophysical WMTI model based on the DKI framework reported on axon water fraction with good accuracy in cases with near normal axon density, but did not provide additional specificity to myelination. Overall, DKI provided additional information regarding white matter microstructure compared with DTI, making it an attractive method for future assessments of white matter development and pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

PubMed

Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

2017-05-01

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

Temperature dependence of water diffusion pools in brain white matter.

PubMed

Dhital, Bibek; Labadie, Christian; Stallmach, Frank; Möller, Harald E; Turner, Robert

2016-02-15

Water diffusion in brain tissue can now be easily investigated using magnetic resonance (MR) techniques, providing unique insights into cellular level microstructure such as axonal orientation. The diffusive motion in white matter is known to be non-Gaussian, with increasing evidence for more than one water-containing tissue compartment. In this study, freshly excised porcine brain white matter was measured using a 125-MHz MR spectrometer (3T) equipped with gradient coils providing magnetic field gradients of up to 35,000 mT/m. The sample temperature was varied between -14 and +19 °C. The hypothesis tested was that white matter contains two slowly exchanging pools of water molecules with different diffusion properties. A Stejskal-Tanner diffusion sequence with very short gradient pulses and b-factors up to 18.8 ms/μm(2) was used. The dependence on b-factor of the attenuation due to diffusion was robustly fitted by a biexponential function, with comparable volume fractions for each component. The diffusion coefficient of each component follows Arrhenius behavior, with significantly different activation energies. The measured volume fractions are consistent with the existence of three water-containing compartments, the first comprising relatively free cytoplasmic and extracellular water molecules, the second of water molecules in glial processes, and the third comprising water molecules closely associated with membranes, as for example, in the myelin sheaths and elsewhere. The activation energy of the slow diffusion pool suggests proton hopping at the surface of membranes by a Grotthuss mechanism, mediated by hydrating water molecules. Copyright © 2015 Elsevier Inc. All rights reserved.

Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits.

PubMed

Finger, Elizabeth Carrie; Marsh, Abigail; Blair, Karina Simone; Majestic, Catherine; Evangelou, Iordanis; Gupta, Karan; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Tovar-Moll, Fernanda; Pine, Daniel; Blair, Robert James

2012-06-30

Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Structural connectivity of neural reward networks in youth at risk for substance use disorders.

PubMed

Squeglia, Lindsay M; Sorg, Scott F; Jacobus, Joanna; Brumback, Ty; Taylor, Charles T; Tapert, Susan F

2015-07-01

Having a positive family history of alcohol use disorders (FHP), as well as aberrant reward circuitry, has been implicated in the initiation of substance use during adolescence. This study explored the relationship between FHP status and reward circuitry in substance naïve youth to better understand future risky behaviors. Participants were 49 FHP and 45 demographically matched family history negative (FHN) substance-naïve 12-14 year-olds (54 % female). Subjects underwent structural magnetic resonance imaging, including diffusion tensor imaging. Nucleus accumbens and orbitofrontal cortex volumes were derived using FreeSurfer, and FSL probabilistic tractography probed structural connectivity and differences in white matter diffusivity estimates (e.g. fractional anisotropy, and mean, radial, and axial diffusivity) between fiber tracts connecting these regions. FHP and FHN youth did not differ on nucleus accumbens or orbitofrontal cortex volumes, white matter tract volumes, or percentages of streamlines (a proxy for fiber tract count) connecting these regions. However, within white matter tracts connecting the nucleus accumbens to the orbitofrontal cortex, FHP youth had significantly lower mean and radial diffusivity (ps < 0.03) than FHN youth. While white matter macrostructure between salience and reward regions did not differ between FHP and FHN youth, FHP youth showed greater white matter coherence within these tracts than FHN youth. Aberrant connectivity between reward regions in FHP youth could be linked to an increased risk for substance use initiation.

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa.

PubMed

Hoare, Jacqueline; Fouche, Jean-Paul; Phillips, Nicole; Joska, John A; Donald, Kirsten A; Thomas, Kevin; Stein, Dan J

2015-04-01

A range of factors contributes to white matter damage in vertically infected HIV-positive children. These may include combination antiretroviral treatment (cART) regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant clinical variables, and cognitive functioning. We explored associations between a number of these factors and diffusion tensor imaging (DTI) measures in 50 cART-treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48 cerebral white matter regions. Significant associations between a number of the clinical variables and white matter integrity were found. Decreased FA, a measure of neuronal damage, was associated with being on second-line cART, low hemoglobin, and younger age. Children with increased MD, a measure of neuronal damage, were younger, had reduced albumin and hemoglobin, and increased viral load. Decreased AD, a measure of axonal damage, was associated with increased viral load and total protein, decreased albumin and hemoglobin, younger age, poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a measure of myelin loss, was associated with younger age, low current CD4 count, low albumin and hemoglobin, and higher viral load and total protein. The current findings underline the possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuroHIV and the importance of examining the effects of HIV disease in the context of treatable clinical variables such as anemia and nutritional status.

Relationship between symptom dimensions and white matter alterations in obsessive-compulsive disorder.

PubMed

Yagi, Michiyo; Hirano, Yoshiyuki; Nakazato, Michiko; Nemoto, Kiyotaka; Ishikawa, Kazuhiro; Sutoh, Chihiro; Miyata, Haruko; Matsumoto, Junko; Matsumoto, Koji; Masuda, Yoshitada; Obata, Takayuki; Iyo, Masaomi; Shimizu, Eiji; Nakagawa, Akiko

2017-06-01

To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

Effect of chorioamnionitis on brain development and injury in premature newborns.

PubMed

Chau, Vann; Poskitt, Kenneth J; McFadden, Deborah E; Bowen-Roberts, Tim; Synnes, Anne; Brant, Rollin; Sargent, Michael A; Soulikias, Wendy; Miller, Steven P

2009-08-01

The association of chorioamnionitis and noncystic white matter injury, a common brain injury in premature newborns, remains controversial. Our objectives were to determine the association of chorioamnionitis and postnatal risk factors with white matter injury, and the effects of chorioamnionitis on early brain development, using advanced magnetic resonance imaging. Ninety-two preterm newborns (24-32 weeks gestation) were studied at a median age of 31.9 weeks and again at 40.3 weeks gestation. Histopathological chorioamnionitis and white matter injury were scored using validated systems. Measures of brain metabolism (N-acetylaspartate/choline and lactate/choline) on magnetic resonance spectroscopy, and microstructure (average diffusivity and fractional anisotropy) on diffusion tensor imaging were calculated from predefined brain regions. Thirty-one (34%) newborns were exposed to histopathological chorioamnionitis, and 26 (28%) had white matter injury. Histopathological chorioamnionitis was not associated with an increased risk of white matter injury (relative risk: 1.2; p = 0.6). Newborns with postnatal infections and hypotension requiring therapy were at higher risk of white matter injury (p < 0.03). Adjusting for gestational age at scan and regions of interest, histopathological chorioamnionitis did not significantly affect brain metabolic and microstructural development (p > 0.1). In contrast, white matter injury was associated with lower N-acetylaspartate/choline (-8.9%; p = 0.009) and lower white matter fractional anisotropy (-11.9%; p = 0.01). Histopathological chorioamnionitis does not appear to be associated with an increased risk of white matter injury on magnetic resonance imaging or with abnormalities of brain development. In contrast, postnatal infections and hypotension are associated with an increased risk of white matter injury in the premature newborn.

The visual white matter: The application of diffusion MRI and fiber tractography to vision science

PubMed Central

Rokem, Ariel; Takemura, Hiromasa; Bock, Andrew S.; Scherf, K. Suzanne; Behrmann, Marlene; Wandell, Brian A.; Fine, Ione; Bridge, Holly; Pestilli, Franco

2017-01-01

Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data. PMID:28196374

Microstructure Imaging of Crossing (MIX) White Matter Fibers from diffusion MRI

PubMed Central

Farooq, Hamza; Xu, Junqian; Nam, Jung Who; Keefe, Daniel F.; Yacoub, Essa; Georgiou, Tryphon; Lenglet, Christophe

2016-01-01

Diffusion MRI (dMRI) reveals microstructural features of the brain white matter by quantifying the anisotropic diffusion of water molecules within axonal bundles. Yet, identifying features such as axonal orientation dispersion, density, diameter, etc., in complex white matter fiber configurations (e.g. crossings) has proved challenging. Besides optimized data acquisition and advanced biophysical models, computational procedures to fit such models to the data are critical. However, these procedures have been largely overlooked by the dMRI microstructure community and new, more versatile, approaches are needed to solve complex biophysical model fitting problems. Existing methods are limited to models assuming single fiber orientation, relevant to limited brain areas like the corpus callosum, or multiple orientations but without the ability to extract detailed microstructural features. Here, we introduce a new and versatile optimization technique (MIX), which enables microstructure imaging of crossing white matter fibers. We provide a MATLAB implementation of MIX, and demonstrate its applicability to general microstructure models in fiber crossings using synthetic as well as ex-vivo and in-vivo brain data. PMID:27982056

Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.

PubMed

Jovicich, Jorge; Marizzoni, Moira; Bosch, Beatriz; Bartrés-Faz, David; Arnold, Jennifer; Benninghoff, Jens; Wiltfang, Jens; Roccatagliata, Luca; Picco, Agnese; Nobili, Flavio; Blin, Oliver; Bombois, Stephanie; Lopes, Renaud; Bordet, Régis; Chanoine, Valérie; Ranjeva, Jean-Philippe; Didic, Mira; Gros-Dagnac, Hélène; Payoux, Pierre; Zoccatelli, Giada; Alessandrini, Franco; Beltramello, Alberto; Bargalló, Núria; Ferretti, Antonio; Caulo, Massimo; Aiello, Marco; Ragucci, Monica; Soricelli, Andrea; Salvadori, Nicola; Tarducci, Roberto; Floridi, Piero; Tsolaki, Magda; Constantinidis, Manos; Drevelegas, Antonios; Rossini, Paolo Maria; Marra, Camillo; Otto, Josephin; Reiss-Zimmermann, Martin; Hoffmann, Karl-Titus; Galluzzi, Samantha; Frisoni, Giovanni B

2014-11-01

Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2 × 2 × 2 mm(3), b = 700 s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7 ± 1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios. Copyright © 2014 Elsevier Inc. All rights reserved.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder.

PubMed

Dean, Douglas C; Travers, Brittany G; Adluru, Nagesh; Tromp, Do P M; Destiche, Daniel J; Samsin, Danica; Prigge, Molly B; Zielinski, Brandon A; Fletcher, P Thomas; Anderson, Jeffrey S; Froehlich, Alyson L; Bigler, Erin D; Lange, Nicholas; Lainhart, Janet E; Alexander, Andrew L

2016-06-01

White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder

PubMed Central

Travers, Brittany G.; Adluru, Nagesh; Tromp, Do P.M.; Destiche, Daniel J.; Samsin, Danica; Prigge, Molly B.; Zielinski, Brandon A.; Fletcher, P. Thomas; Anderson, Jeffrey S.; Froehlich, Alyson L.; Bigler, Erin D.; Lange, Nicholas; Lainhart, Janet E.; Alexander, Andrew L.

2016-01-01

Abstract White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD. PMID:27021440

Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation.

PubMed

Svolos, P; Reddick, W E; Edwards, A; Sykes, A; Li, Y; Glass, J O; Patay, Z

2017-06-01

Assessing the response to treatment in infiltrative brain tumors by using lesion volume-based response criteria is challenging. We hypothesized that in such tumors, volume measurements alone may not accurately capture changes in actual tumor burden during treatment. We longitudinally evaluated volume changes in both normal-appearing supratentorial white matter and the brain stem lesions in patients treated for diffuse intrinsic pontine glioma to determine to what extent adjuvant systemic therapies may skew the accuracy of tumor response assessments based on volumetric analysis. The anatomic MR imaging and diffusion tensor imaging data of 26 patients with diffuse intrinsic pontine glioma were retrospectively analyzed. Treatment included conformal radiation therapy in conjunction with vandetanib and dexamethasone. Volumetric and diffusion data were analyzed with time, and differences between time points were evaluated statistically. Normalized brain stem lesion volume decreased during combined treatment (slope = -0.222, P < .001) and increased shortly after completion of radiation therapy (slope = 0.422, P < .001). Supratentorial white matter volume steadily and significantly decreased with time (slope = -0.057, P < .001). Longitudinal changes in brain stem lesion volume are robust; less pronounced but measurable changes occur in the supratentorial white matter. Volume changes in nonirradiated supratentorial white matter during the disease course reflect the effects of systemic medication on the water homeostasis of normal parenchyma. Our data suggest that adjuvant nontumor-targeted therapies may have a more substantial effect on lesion volume changes than previously thought; hence, an apparent volume decrease in infiltrative tumors receiving combined therapies may lead to overestimation of the actual response and tumor control. © 2017 by American Journal of Neuroradiology.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

PubMed

Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

2015-07-01

Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.

Brain aging in humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta): magnetic resonance imaging studies of macro- and microstructural changes

PubMed Central

Chen, Xu; Errangi, Bhargav; Li, Longchuan; Glasser, Matthew F.; Westlye, Lars T.; Fjell, Anders M.; Walhovd, Kristine B.; Hu, Xiaoping; Herndon, James G.; Preuss, Todd M.; Rilling, James K.

2013-01-01

Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but this decrease occurred proportionally later in the chimpanzee lifespan than in humans. Diffusion MRI revealed widespread age-related decreases in fractional anisotropy and increases in radial diffusivity in chimpanzees and macaques. However, both the fractional anisotropy decline and the radial diffusivity increase started at a proportionally earlier age in humans than in chimpanzees. Thus, even though overall patterns of gray and white matter aging are similar in humans and chimpanzees, the longer lifespan of humans provides more time for white matter to deteriorate before death, with the result that some neurological effects of aging may be exacerbated in our species. PMID:23623601

In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy.

PubMed

van Eijsden, Pieter; Otte, Wim M; van der Hel, W Saskia; van Nieuwenhuizen, Onno; Dijkhuizen, Rick M; de Graaf, Robin A; Braun, Kees P J

2011-04-01

Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile rats, 4 and 8 weeks after pilocarpine-induced status epilepticus (SE). In the medial corpus callosum (CC), mean diffusivity and axial diffusivity (MD and λ₁) as well as a myelin staining were significantly reduced at 4 weeks. Only the λ₁ decrease persisted at 8 weeks. In the fornix fimbriae (FF), λ₁ and myelin staining were decreased at both time points, whereas fractional anisotropy (FA) and MD were significantly reduced at 8 weeks only. We conclude that SE induces both transient and chronic white matter changes in the medial CC and FF that are to some degree related to myelin pathology. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.

PubMed

Arrigo, Alessandro; Calamuneri, Alessandro; Milardi, Demetrio; Mormina, Enricomaria; Rania, Laura; Postorino, Elisa; Marino, Silvia; Di Lorenzo, Giuseppe; Anastasi, Giuseppe Pio; Ghilardi, Maria Felice; Aragona, Pasquale; Quartarone, Angelo; Gaeta, Michele

2017-12-01

Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes (P < .05). Moreover, the chiasmatic area and volume were significantly reduced (P < .05). Conclusion The findings show that visual system alterations can be detected in early stages of Parkinson disease and that the entire intracranial visual system can be involved. © RSNA, 2017 Online supplemental material is available for this article.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

PubMed

Zikou, Anastasia K; Xydis, Vasileios G; Astrakas, Loukas G; Nakou, Iliada; Tzarouchi, Loukia C; Tzoufi, Meropi; Argyropoulou, Maria I

2016-07-01

There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

White Matter Changes and Confrontation Naming in Retired Aging National Football League Athletes.

PubMed

Strain, Jeremy F; Didehbani, Nyaz; Spence, Jeffrey; Conover, Heather; Bartz, Elizabeth K; Mansinghani, Sethesh; Jeroudi, Myrtle K; Rao, Neena K; Fields, Lindy M; Kraut, Michael A; Cullum, C Munro; Hart, John; Womack, Kyle B

2017-01-15

Using diffusion tensor imaging (DTI), we assessed the relationship of white matter integrity and performance on the Boston Naming Test (BNT) in a group of retired professional football players and a control group. We examined correlations between fractional anisotropy (FA) and mean diffusivity (MD) with BNT T-scores in an unbiased voxelwise analysis processed with tract-based spatial statistics (TBSS). We also analyzed the DTI data by grouping voxels together as white matter tracts and testing each tract's association with BNT T-scores. Significant voxelwise correlations between FA and BNT performance were only seen in the retired football players (p < 0.02). Two tracts had mean FA values that significantly correlated with BNT performance: forceps minor and forceps major. White matter integrity is important for distributed cognitive processes, and disruption correlates with diminished performance in athletes exposed to concussive and subconcussive brain injuries, but not in controls without such exposure.

Medial frontal white and gray matter contributions to general intelligence.

PubMed

Ohtani, Toshiyuki; Nestor, Paul G; Bouix, Sylvain; Saito, Yukiko; Hosokawa, Taiga; Kubicki, Marek

2014-01-01

The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%-34% of the variance in IQ, in comparison to 11%-16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence.

Severe cerebral white matter involvement in a case of dentatorubropallidoluysian atrophy studied at autopsy.

PubMed

Muñoz, Esteban; Campdelacreu, Jaume; Ferrer, Isidre; Rey, María J; Cardozo, Adriana; Gómez, Beatriz; Tolosa, Eduardo

2004-06-01

The pathophysiology of white matter involvement in dentatorubropallidoluysian atrophy (DRPLA) is controversial. Moreover, the clinical repercussions and evolution of these lesions have not been well documented. To describe a case of DRPLA with severe cerebellar white matter involvement. Case report. Patient A 62-year-old woman with DRPLA. When the genetic diagnosis was made, the patient manifested severe ataxia, slight dysarthria, and subcortical cognitive impairment. Cranial magnetic resonance imaging showed atrophy of the cerebellum and brainstem and moderate high-intensity signal alterations in the periventricular cerebral white matter in T2-weighted sequences. In the following 5 years, she developed uncontrolled head movements associated with severe bruxism and tetraparesis, and became deeply demented. New magnetic resonance imaging showed severe diffuse cerebral white matter alterations in T2 sequences with only slight progression of brainstem and cerebellar atrophy. After her death at 67 years of age, the autopsy study showed diffuse myelin pallor, axonal preservation, and reactive astrogliosis in the cerebral white matter, with only mild atherosclerotic changes, and moderate neuronal loss in the cerebellum and brainstem. Leukoencephalopathy could be a prominent finding in some patients with DRPLA, explaining, at least in part, their clinical evolution. In our case, the disproportion between the severity of white matter damage and vascular changes does not support a cardinal role for ischemic mechanisms in leukoencephalopathy.

Persistence of abnormalities in white matter in children with type 1 diabetes.

PubMed

Fox, Larry A; Hershey, Tamara; Mauras, Nelly; Arbeláez, Ana Maria; Tamborlane, William V; Buckingham, Bruce; Tsalikian, Eva; Englert, Kim; Raman, Mira; Jo, Booil; Shen, Hanyang; Reiss, Allan; Mazaika, Paul

2018-07-01

Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes. One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA 1c levels were obtained every 3 months. Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02). These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.

Differences in integrity of white matter and changes with training in spelling impaired children: a diffusion tensor imaging study

PubMed Central

Gebauer, D.; Fink, A.; Filippini, N.; Johansen-Berg, H.; Reishofer, G.; Koschutnig, K.; Kargl, R.; Purgstaller, C.; Fazekas, F.; Enzinger, C.

2013-01-01

While the functional correlates of spelling impairment have been rarely investigated, to our knowledge no study exists regarding the structural characteristics of spelling impairment and potential changes with interventions. Using diffusion tensor imaging at 3.0 T, we here therefore sought to investigate (a) differences between children with poor spelling abilities (training group and waiting group) and controls, and (b) the effects of a morpheme- based spelling intervention in children with poor spelling abilities on DTI parameters. A baseline comparison of white matter indices revealed significant differences between controls and spelling-impaired children, mainly located in the right hemisphere (superior corona radiata (SCR), posterior limb of internal capsule, superior longitudinal fasciculus). After 5 weeks of training, spelling ability improved in the training group, along with increases in fractional anisotropy and decreases of radial diffusivity in the right hemisphere compared to controls. In addition, significantly higher decreases of mean diffusivity in the right SCR for the spelling-impaired training group compared to the waiting group were observed. Our results suggest that spelling impairment is associated with differences in white-matter integrity in the right hemisphere. We also provide first indications that white matter changes occur during successful training, but this needs to be more specifically addressed in future research. PMID:22198594

Differences in integrity of white matter and changes with training in spelling impaired children: a diffusion tensor imaging study.

PubMed

Gebauer, D; Fink, A; Filippini, N; Johansen-Berg, H; Reishofer, G; Koschutnig, K; Kargl, R; Purgstaller, C; Fazekas, F; Enzinger, C

2012-07-01

While the functional correlates of spelling impairment have been rarely investigated, to our knowledge no study exists regarding the structural characteristics of spelling impairment and potential changes with interventions. Using diffusion tensor imaging at 3.0 T, we here therefore sought to investigate (a) differences between children with poor spelling abilities (training group and waiting group) and controls, and (b) the effects of a morpheme-based spelling intervention in children with poor spelling abilities on DTI parameters. A baseline comparison of white matter indices revealed significant differences between controls and spelling-impaired children, mainly located in the right hemisphere (superior corona radiata (SCR), posterior limb of internal capsule, superior longitudinal fasciculus). After 5 weeks of training, spelling ability improved in the training group, along with increases in fractional anisotropy and decreases of radial diffusivity in the right hemisphere compared to controls. In addition, significantly higher decreases of mean diffusivity in the right SCR for the spelling-impaired training group compared to the waiting group were observed. Our results suggest that spelling impairment is associated with differences in white-matter integrity in the right hemisphere. We also provide first indications that white matter changes occur during successful training, but this needs to be more specifically addressed in future research.

Sensitive period for white-matter connectivity of superior temporal cortex in deaf people.

PubMed

Li, Yanyan; Ding, Guosheng; Booth, James R; Huang, Ruiwang; Lv, Yating; Zang, Yufeng; He, Yong; Peng, Danling

2012-02-01

Previous studies have shown that white matter in the deaf brain changes due to hearing loss. However, how white-matter development is influenced by early hearing experience of deaf people is still unknown. Using diffusion tensor imaging and tract-based spatial statistics, we compared white-matter structures among three groups of subjects including 60 congenitally deaf individuals, 36 acquired deaf (AD) individuals, and 38 sex- and age-matched hearing controls (HC). The result showed that the deaf individuals had significantly reduced fractional anisotropy (FA) values in bilateral superior temporal cortex and the splenium of corpus callosum compared to HC. The reduction of FA values in acquired deafness correlated with onset age of deafness, but not the duration of deafness. To explore the underlying mechanism of FA changes in the deaf groups, we further analyzed radial and axial diffusivities and found that (1) the reduced FA values in deaf individuals compared to HC is primarily driven by higher radial diffusivity values and (2) in the AD, higher radial diffusivity was correlated with earlier onset age of deafness, but not the duration of deafness. These findings imply that early sensory experience is critical for the growth of fiber myelination, and anatomical reorganization following auditory deprivation is sensitive to early plasticity in the brain. Copyright © 2010 Wiley Periodicals, Inc.

An MRI study of white matter tract integrity in regular cannabis users: effects of cannabis use and age.

PubMed

Jakabek, David; Yücel, Murat; Lorenzetti, Valentina; Solowij, Nadia

2016-10-01

Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies sampling older cannabis users. We recruited a sample with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The integrity of tracts was assessed using average fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion measures were compared between users and non-users and as group-by-age interactions. Correlations between diffusion measures and age of onset, duration, frequency and dose of current cannabis use were examined. Cannabis users overall had lower fractional anisotropy than healthy non-users in the forceps minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences observed. Younger users showed predominantly reduced axial diffusivity, whereas older users had higher radial diffusivity in widespread tracts. Higher axial diffusivity was associated with duration of cannabis use in the cingulum angular bundle (beta = 5.00 × 10(-5), p = .003). Isolated higher AD in older cannabis users was also observed. The findings suggest that exogenous cannabinoids alter normal brain maturation, with differing effects at various neurodevelopmental stages of life. These age-related differences are posited to account for the disparate results described in the literature.

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure.

PubMed

Pastura, Giuseppe; Doering, Thomas; Gasparetto, Emerson Leandro; Mattos, Paulo; Araújo, Alexandra Prüfer

2016-06-01

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults

PubMed Central

Paul, Robert H.; Grieve, Stuart M.; Niaura, Raymond; David, Sean P.; Laidlaw, David H.; Cohen, Ronald; Sweet, Lawrence; Taylor, George; Clark, C. Richard; Pogun, Sakire; Gordon, Evian

2008-01-01

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers. PMID:18188754

Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users.

PubMed

Willi, Taylor S; Barr, Alasdair M; Gicas, Kristina; Lang, Donna J; Vila-Rodriguez, Fidel; Su, Wayne; Thornton, Allen E; Leonova, Olga; Giesbrecht, Chantelle J; Procyshyn, Ric M; Rauscher, Alexander; MacEwan, William G; Honer, William G; Panenka, William J

2017-05-01

With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as 'substance-induced psychosis' (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine-associated psychosis (CAP; n = 24) and a cocaine-dependent non-psychotic (CDN) group (n = 43). Tract-based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto-temporal, fronto-thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis. © 2016 Society for the Study of Addiction.

The relationship between functional magnetic resonance imaging activation, diffusion tensor imaging, and training effects.

PubMed

Farrar, Danielle; Budson, Andrew E

2017-04-01

While the relationship between diffusion tensor imaging (DTI) measurements and training effects is explored by Voelker et al. (this issue), a cursory discussion of functional magnetic resonance imaging (fMRI) measurements categorizes increased activation with findings of greater white matter integrity. Evidence of the relationship between fMRI activation and white matter integrity is conflicting, as is the relationship between fMRI activation and training effects. An examination of the changes in fMRI activation in response to training is helpful, but the relationship between DTI and fMRI activation, particularly in the context of white matter changes, must be examined further before general conclusions can be drawn.

A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER

PubMed Central

Delaparte, Lauren; Yeh, Fang‐Cheng; DeLorenzo, Christine; McGrath, Patrick J.; Weissman, Myrna M.; Adams, Phillip; Fava, Maurizio; Deckersbach, Thilo; McInnis, Melvin G.; Carmody, Thomas J.; Cooper, Crystal M.; Kurian, Benji T.; Lu, Hanzhang; Toups, Marisa S.; Trivedi, Madhukar H.; Parsey, Ramin V.

2015-01-01

Background Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract‐based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. Results There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. Conclusions The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts. PMID:26477532

White Matter Hyperintensities and Changes in White Matter Integrity in Patients with Alzheimer’s Disease

PubMed Central

Wang, Liya; Goldstein, Felicia C.; Levey, Allan I.; Lah, James J.; Meltzer, Carolyn C.; Holder, Chad A.; Mao, Hui

2012-01-01

Purpose White matter hyperintensities (WMHs) are a risk factor for Alzheimer’s disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. Subjects and Methods Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR) and axial diffusivity (DA) were analyzed using the region of interest and Tract-Based Spatial Statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. Results AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and DR were more sensitive measurements than MD and DA in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. Conclusions WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. DR may serve as an imaging marker of myelin deficits associated with AD. PMID:21152911

Normal development of human brain white matter from infancy to early adulthood: a diffusion tensor imaging study.

PubMed

Uda, Satoshi; Matsui, Mie; Tanaka, Chiaki; Uematsu, Akiko; Miura, Kayoko; Kawana, Izumi; Noguchi, Kyo

2015-01-01

Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood. © 2015 S. Karger AG, Basel.

Diffusion Tensor Imaging of Frontal White Matter and Executive Functioning in Cocaine-Exposed Children

PubMed Central

Warner, Tamara Duckworth; Behnke, Marylou; Eyler, Fonda Davis; Padgett, Kyle; Leonard, Christiana; Hou, Wei; Garvan, Cynthia Wilson; Schmalfuss, Ilona M.; Blackband, Stephen J.

2011-01-01

BACKGROUND Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. METHODS Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). RESULTS Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. CONCLUSIONS Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research. PMID:17079574

Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children.

PubMed

Warner, Tamara Duckworth; Behnke, Marylou; Eyler, Fonda Davis; Padgett, Kyle; Leonard, Christiana; Hou, Wei; Garvan, Cynthia Wilson; Schmalfuss, Ilona M; Blackband, Stephen J

2006-11-01

Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.

Atypical white-matter microstructure in congenitally deaf adults: A region of interest and tractography study using diffusion-tensor imaging.

PubMed

Karns, Christina M; Stevens, Courtney; Dow, Mark W; Schorr, Emily M; Neville, Helen J

2017-01-01

Considerable research documents the cross-modal reorganization of auditory cortices as a consequence of congenital deafness, with remapped functions that include visual and somatosensory processing of both linguistic and nonlinguistic information. Structural changes accompany this cross-modal neuroplasticity, but precisely which specific structural changes accompany congenital and early deafness and whether there are group differences in hemispheric asymmetries remain to be established. Here, we used diffusion tensor imaging (DTI) to examine microstructural white matter changes accompanying cross-modal reorganization in 23 deaf adults who were genetically, profoundly, and congenitally deaf, having learned sign language from infancy with 26 hearing controls who participated in our previous fMRI studies of cross-modal neuroplasticity. In contrast to prior literature using a whole-brain approach, we introduce a semiautomatic method for demarcating auditory regions in which regions of interest (ROIs) are defined on the normalized white matter skeleton for all participants, projected into each participants native space, and manually constrained to anatomical boundaries. White-matter ROIs were left and right Heschl's gyrus (HG), left and right anterior superior temporal gyrus (aSTG), left and right posterior superior temporal gyrus (pSTG), as well as one tractography-defined region in the splenium of the corpus callosum connecting homologous left and right superior temporal regions (pCC). Within these regions, we measured fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and white-matter volume. Congenitally deaf adults had reduced FA and volume in white matter structures underlying bilateral HG, aSTG, pSTG, and reduced FA in pCC. In HG and pCC, this reduction in FA corresponded with increased RD, but differences in aSTG and pSTG could not be localized to alterations in RD or AD. Direct statistical tests of hemispheric asymmetries in these differences indicated the most prominent effects in pSTG, where the largest differences between groups occurred in the right hemisphere. Other regions did not show significant hemispheric asymmetries in group differences. Taken together, these results indicate that atypical white matter microstructure and reduced volume underlies regions of superior temporal primary and association auditory cortex and introduce a robust method for quantifying volumetric and white matter microstructural differences that can be applied to future studies of special populations. Published by Elsevier B.V.

Diffusion measures indicate fight exposure-related damage to cerebral white matter in boxers and mixed martial arts fighters.

PubMed

Shin, W; Mahmoud, S Y; Sakaie, K; Banks, S J; Lowe, M J; Phillips, M; Modic, M T; Bernick, C

2014-02-01

Traumatic brain injury is common in fighting athletes such as boxers, given the frequency of blows to the head. Because DTI is sensitive to microstructural changes in white matter, this technique is often used to investigate white matter integrity in patients with traumatic brain injury. We hypothesized that previous fight exposure would predict DTI abnormalities in fighting athletes after controlling for individual variation. A total of 74 boxers and 81 mixed martial arts fighters were included in the analysis and scanned by use of DTI. Individual information and data on fight exposures, including number of fights and knockouts, were collected. A multiple hierarchical linear regression model was used in region-of-interest analysis to test the hypothesis that fight-related exposure could predict DTI values separately in boxers and mixed martial arts fighters. Age, weight, and years of education were controlled to ensure that these factors would not account for the hypothesized effects. We found that the number of knockouts among boxers predicted increased longitudinal diffusivity and transversal diffusivity in white matter and subcortical gray matter regions, including corpus callosum, isthmus cingulate, pericalcarine, precuneus, and amygdala, leading to increased mean diffusivity and decreased fractional anisotropy in the corresponding regions. The mixed martial arts fighters had increased transversal diffusivity in the posterior cingulate. The number of fights did not predict any DTI measures in either group. These findings suggest that the history of fight exposure in a fighter population can be used to predict microstructural brain damage.

Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

PubMed

Brockmann, Knut; Dreha-Kulaczewski, Steffi; Dechent, Peter; Bönnemann, Carsten; Helms, Gunther; Kyllerman, Marten; Brück, Wolfgang; Frahm, Jens; Huehne, Kathrin; Gärtner, Jutta; Rautenstrauss, Bernd

2008-07-01

Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination.

Aortic stiffness is associated with white matter integrity in patients with type 1 diabetes.

PubMed

Tjeerdema, Nathanja; Van Schinkel, Linda D; Westenberg, Jos J; Van Elderen, Saskia G; Van Buchem, Mark A; Smit, Johannes W; Van der Grond, Jeroen; De Roos, Albert

2014-09-01

To assess the association between aortic pulse wave velocity (PWV) as a marker of arterial stiffness and diffusion tensor imaging of brain white matter integrity in patients with type 1 diabetes using advanced magnetic resonance imaging (MRI) technology. Forty-one patients with type 1 diabetes (23 men, mean age 44 ± 12 years, mean diabetes duration 24 ± 13 years) were included. Aortic PWV was assessed using through-plane velocity-encoded MRI. Brain diffusion tensor imaging (DTI) measurements were performed on 3-T MRI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated for white and grey matter integrity. Pearson correlation and multivariable linear regression analyses including cardiovascular risk factors as covariates were assessed. Multivariable linear regression analyses revealed that aortic PWV is independently associated with white matter integrity FA (β = -0.777, p = 0.008) in patients with type 1 diabetes. This effect was independent of age, gender, mean arterial pressure, body mass index, smoking, duration of diabetes and glycated haemoglobin levels. Aortic PWV was not significantly related to grey matter integrity. Our data suggest that aortic stiffness is independently associated with reduced white matter integrity in patients with type 1 diabetes. Aortic stiffness is associated with brain injury. Aortic stiffness exposes small vessels to high pressure fluctuations and flow. Aortic stiffness is associated with microvascular brain injury in diabetes. This suggests a vascular contribution to early subtle microstructural deficits.

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study.

PubMed

Otte, Willem M; van der Marel, Kajo; van Meer, Maurits P A; van Rijen, Peter C; Gosselaar, Peter H; Braun, Kees P J; Dijkhuizen, Rick M

2015-08-01

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.

PubMed

Choi, Bo-Ryoung; Kim, Dong-Hee; Back, Dong Bin; Kang, Chung Hwan; Moon, Won-Jin; Han, Jung-Soo; Choi, Dong-Hee; Kwon, Kyoung Ja; Shin, Chan Young; Kim, Bo-Ram; Lee, Jongmin; Han, Seol-Heui; Kim, Hahn Young

2016-02-01

Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia. © 2015 American Heart Association, Inc.

Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline.

PubMed

Charlton, R A; Schiavone, F; Barrick, T R; Morris, R G; Markus, H S

2010-01-01

Diffusion tensor imaging (DTI) is a sensitive method for detecting white matter damage, and in cross sectional studies DTI measures correlate with age related cognitive decline. However, there are few data on whether DTI can detect age related changes over short time periods and whether such change correlates with cognitive function. In a community sample of 84 middle-aged and elderly adults, MRI and cognitive testing were performed at baseline and after 2 years. Changes in DTI white matter histograms, white matter hyperintensity (WMH) volume and brain volume were determined. Change over time in performance on tests of executive function, working memory and information processing speed were also assessed. Significant change in all MRI measures was detected. For cognition, change was detected for working memory and this correlated with change in DTI only. In a stepwise regression, with change in working memory as the dependent variable, a DTI histogram measure explained 10.8% of the variance in working memory. Change in WMH or brain volume did not contribute to the model. DTI is sensitive to age related change in white matter ultrastructure and appears useful for monitoring age related white matter change even over short time periods.

Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

2014-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

[Research on brain white matter network in cerebral palsy infant].

PubMed

Li, Jun; Yang, Cheng; Wang, Yuanjun; Nie, Shengdong

2017-10-01

Present study used diffusion tensor image and tractography to construct brain white matter networks of 15 cerebral palsy infants and 30 healthy infants that matched for age and gender. After white matter network analysis, we found that both cerebral palsy and healthy infants had a small-world topology in white matter network, but cerebral palsy infants exhibited abnormal topological organization: increased shortest path length but decreased normalize clustering coefficient, global efficiency and local efficiency. Furthermore, we also found that white matter network hub regions were located in the left cuneus, precuneus, and left posterior cingulate gyrus. However, some abnormal nodes existed in the frontal, temporal, occipital and parietal lobes of cerebral palsy infants. These results indicated that the white matter networks for cerebral palsy infants were disrupted, which was consistent with previous studies about the abnormal brain white matter areas. This work could help us further study the pathogenesis of cerebral palsy infants.

Evaluation and statistical inference for human connectomes.

PubMed

Pestilli, Franco; Yeatman, Jason D; Rokem, Ariel; Kay, Kendrick N; Wandell, Brian A

2014-10-01

Diffusion-weighted imaging coupled with tractography is currently the only method for in vivo mapping of human white-matter fascicles. Tractography takes diffusion measurements as input and produces the connectome, a large collection of white-matter fascicles, as output. We introduce a method to evaluate the evidence supporting connectomes. Linear fascicle evaluation (LiFE) takes any connectome as input and predicts diffusion measurements as output, using the difference between the measured and predicted diffusion signals to quantify the prediction error. We use the prediction error to evaluate the evidence that supports the properties of the connectome, to compare tractography algorithms and to test hypotheses about tracts and connections.

White matter deficits assessed by diffusion tensor imaging and cognitive dysfunction in psychostimulant users with comorbid human immunodeficiency virus infection.

PubMed

Tang, Victor M; Lang, Donna J; Giesbrecht, Chantelle J; Panenka, William J; Willi, Taylor; Procyshyn, Ric M; Vila-Rodriguez, Fidel; Jenkins, Willough; Lecomte, Tania; Boyda, Heidi N; Aleksic, Ana; MacEwan, G William; Honer, William G; Barr, Alasdair M

2015-09-30

Psychostimulant drug use is commonly associated with drug-related infection, including the human immunodeficiency virus (HIV). Both psychostimulant use and HIV infection are known to damage brain white matter and impair cognition. To date, no study has examined white matter integrity using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in chronic psychostimulant users with comorbid HIV infection, and determined the relationship of white matter integrity to cognitive function. Twenty-one subjects (mean age 37.5 ± 9.0 years) with a history of heavy psychostimulant use and HIV infection (8.7 ± 4.3 years) and 22 matched controls were scanned on a 3T MRI. Fractional anisotropy (FA) values were calculated with DTI software. Four regions of interest were manually segmented, including the genu of the corpus callosum, left and right anterior limbs of the internal capsule, and the anterior commissure. Subjects also completed a neurocognitive battery and questionnaires about physical and mental health. The psychostimulant using, HIV positive group displayed decreased white matter integrity, with significantly lower FA values for all white matter tracts (p < 0.05). This group also exhibited decreased cognitive performance on tasks that assessed cognitive set-shifting, fine motor speed and verbal memory. FA values for the white matter tracts correlated with cognitive performance on many of the neurocognitive tests. White matter integrity was thus impaired in subjects with psychostimulant use and comorbid HIV infection, which predicted worsened cognitive performance on a range of tests. Further study on this medical comorbidity is required.

White matter fiber integrity of the saccadic eye movement network differs between schizophrenia and healthy groups.

PubMed

Schaeffer, David J; Rodrigue, Amanda L; Burton, Courtney R; Pierce, Jordan E; Murphy, Megan N; Clementz, Brett A; McDowell, Jennifer E

2017-12-01

Recent diffusion tensor imaging (DTI) studies suggest that altered white matter fiber integrity is a pathophysiological feature of schizophrenia. Lower white matter integrity is associated with poor cognitive control, a characteristic of schizophrenia that can be measured using antisaccade tasks. Although the functional neural correlates of poor antisaccade performance have been well documented, fewer studies have investigated the extent to which white matter fibers connecting the functional nodes of this network contribute to antisaccade performance. The aim of the present study was to assess the white matter structural integrity of fibers connecting two functional nodes (putamen and medial frontal eye fields) of the saccadic eye movement network implicated in poor antisaccade performance in schizophrenia. To evaluate white matter integrity, DTI was acquired on subjects with schizophrenia and two comparison groups: (a) behaviorally matched healthy comparison subjects with low levels of cognitive control (LCC group), and (b) healthy subjects with high levels of cognitive control (HCC group). White matter fibers were tracked between functional regions of interest generated from antisaccade fMRI activation maps, and measures of diffusivity were quantified. The results demonstrated lower white matter integrity in the schizophrenia group than in the HCC group, but not the LCC group who showed similarly poor cognitive control performance. Overall, the results suggest that these alterations are not specific to the disease process of schizophrenia, but may rather be a function of uncontrolled cognitive factors that are concomitant with the disease but also observed in some healthy people. © 2017 Society for Psychophysiological Research.

Region of Interest Correction Factors Improve Reliability of Diffusion Imaging Measures Within and Across Scanners and Field Strengths

PubMed Central

Venkatraman, Vijay K; Gonzalez, Christopher E.; Landman, Bennett; Goh, Joshua; Reiter, David A.; An, Yang; Resnick, Susan M.

2017-01-01

Diffusion tensor imaging (DTI) measures are commonly used as imaging markers to investigate individual differences in relation to behavioral and health-related characteristics. However, the ability to detect reliable associations in cross-sectional or longitudinal studies is limited by the reliability of the diffusion measures. Several studies have examined reliability of diffusion measures within (i.e. intra-site) and across (i.e. inter-site) scanners with mixed results. Our study compares the test-retest reliability of diffusion measures within and across scanners and field strengths in cognitively normal older adults with a follow-up interval less than 2.25 years. Intra-class correlation (ICC) and coefficient of variation (CoV) of fractional anisotropy (FA) and mean diffusivity (MD) were evaluated in sixteen white matter and twenty-six gray matter bilateral regions. The ICC for intra-site reliability (0.32 to 0.96 for FA and 0.18 to 0.95 for MD in white matter regions; 0.27 to 0.89 for MD and 0.03 to 0.79 for FA in gray matter regions) and inter-site reliability (0.28 to 0.95 for FA in white matter regions, 0.02 to 0.86 for MD in gray matter regions) with longer follow-up intervals were similar to earlier studies using shorter follow-up intervals. The reliability of across field strengths comparisons was lower than intra- and inter-site reliability. Within and across scanner comparisons showed that diffusion measures were more stable in larger white matter regions (> 1500 mm3). For gray matter regions, the MD measure showed stability in specific regions and was not dependent on region size. Linear correction factor estimated from cross-sectional or longitudinal data improved the reliability across field strengths. Our findings indicate that investigations relating diffusion measures to external variables must consider variable reliability across the distinct regions of interest and that correction factors can be used to improve consistency of measurement across field strengths. An important result of this work is that inter-scanner and field strength effects can be partially mitigated with linear correction factors specific to regions of interest. These data-driven linear correction techniques can be applied in cross-sectional or longitudinal studies. PMID:26146196

Dimensions of Attention Associated With the Microstructure of Corona Radiata White Matter.

PubMed

Stave, Elise A; De Bellis, Michael D; Hooper, Steven R; Woolley, Donald P; Chang, Suk Ki; Chen, Steven D

2017-04-01

Mirsky proposed a model of attention that included these dimensions: focus/execute, sustain, stabilize, encode, and shift. The neural correlates of these dimensions were investigated within corona radiata subregions in healthy youth. Diffusion tensor imaging and neuropsychological assessments were conducted in 79 healthy, right-handed youth aged 4-17 years. Diffusion tensor imaging maps were analyzed using standardized parcellation methods. Partial Pearson correlations between neuropsychological standardized scores, representing these attention dimensions, and diffusion tensor imaging measures of corona radiata subregions were calculated after adjusting for gender and IQ. Significant correlations were found between the focus/execute, sustain, stabilize, and shift dimensions and imaging metrics in hypothesized corona radiata subregions. Results suggest that greater microstructural white matter integrity of the corona radiata is partly associated with attention across 4 attention dimensions. Findings suggest that white matter microstructure of the corona radiata is a neural correlate of several, but not all, attention dimensions.

Dimensions of Attention Associated with the Microstructure of Corona Radiata White Matter

PubMed Central

Stave, Elise A.; Hooper, Stephen R.; Woolley, Donald P.; Chang, Suk Ki; Chen, Steven D.

2016-01-01

Mirsky proposed a model of attention that included these dimensions: focus/execute, sustain, stabilize, encode, and shift. The neural correlates of these dimensions were investigated within corona radiate subregions in healthy youth. Diffusion tensor imaging and neuropsychological assessments were conducted in 79 healthy, right-handed youth aged 4–17 years. Diffusion tensor imaging maps were analyzed using standardized parcellation methods. Partial Pearson correlations between neuropsychological standardized scores, representing these attention dimensions, and diffusion tensor imaging measures of corona radiate subregions were calculated after adjusting for gender and IQ. Significant correlations were found between the focus/execute, sustain, stabilize and shift dimensions and imaging metrics in hypothesized corona radiate subregions. Results suggest that greater microstructural white matter integrity of the corona radiata is partly associated with attention across four attention dimensions. Findings suggest that white matter microstructure of the corona radiata is a neural correlate of several, but not all, attention dimensions. PMID:28090797

Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe.

PubMed

Huang, J; Friedland, R P; Auchus, A P

2007-01-01

Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. We used DTI to characterize microstructural white matter changes and their associations with cognitive dysfunction in Alzheimer disease (AD) and mild cognitive impairment (MCI). We studied elderly subjects with mild AD (n = 6), MCI (n = 11), or normal cognition (n = 8). A standardized clinical and neuropsychological evaluation was conducted on each subject. DTI images were acquired, and fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) of normal-appearing white matter (NAWM) in frontal, temporal, parietal, and occipital lobes were determined. These diffusion measurements were compared across the 3 groups, and significant differences were further examined for correlations with tests of cognitive function. Compared with normal controls, AD subjects demonstrated decreased FA and increased DR in the temporal, parietal, and frontal NAWM and decreased DA in temporal NAWM. MCI subjects also showed decreased FA and decreased DA in temporal NAWM, with decreased FA and increased DR in parietal NAWM. Diffusion measurements showed no differences in occipital NAWM. Across all subjects, temporal lobe FA and DR correlated with episodic memory, frontal FA and DR correlated with executive function, and parietal DR significantly correlated with visuospatial ability. We found evidence for functionally relevant microstructural changes in the NAWM of patients with AD and MCI. These changes were present in brain regions serving higher cortical functions, but not in regions serving primary functions, and are consistent with a hypothesized loss of axonal processes in the temporal lobe.

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia.

PubMed

Alloza, Clara; Cox, Simon R; Duff, Barbara; Semple, Scott I; Bastin, Mark E; Whalley, Heather C; Lawrie, Stephen M

2016-08-30

Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10-0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Natural biological variation of white matter microstructure is accentuated in Huntington's disease.

PubMed

Gregory, Sarah; Crawford, Helen; Seunarine, Kiran; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Scahill, Rachael I; Tabrizi, Sarah J; Rees, Geraint; Langbehn, Douglas; Orth, Michael

2018-04-22

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG-repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome-wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties, on HD pathogenesis could provide a complementary approach to understanding disease modification. We have previously shown that while white matter diffusivity patterns in the left sensorimotor network were similar in controls and HD gene-carriers, they were more extreme in the HD group. We hypothesized that the influence of natural variation in diffusivity on effects of HD pathogenesis on white matter is not limited to the sensorimotor network but extends to cognitive, limbic, and visual networks. Using tractography, we investigated 32 bilateral pathways within HD-related networks, including motor, cognitive, and limbic, and examined diffusivity metrics using principal components analysis. We identified three independent patterns of diffusivity common to controls and HD gene-carriers that predicted HD status. The first pattern involved almost all tracts, the second was limited to sensorimotor tracts, and the third encompassed cognitive network tracts. Each diffusivity pattern was associated with network specific performance. The consistency in diffusivity patterns across both groups coupled with their association with disease status and task performance indicates that naturally-occurring patterns of diffusivity can become accentuated in the presence of the HD gene mutation to influence clinical brain function. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

FADTTS: functional analysis of diffusion tensor tract statistics.

PubMed

Zhu, Hongtu; Kong, Linglong; Li, Runze; Styner, Martin; Gerig, Guido; Lin, Weili; Gilmore, John H

2011-06-01

The aim of this paper is to present a functional analysis of a diffusion tensor tract statistics (FADTTS) pipeline for delineating the association between multiple diffusion properties along major white matter fiber bundles with a set of covariates of interest, such as age, diagnostic status and gender, and the structure of the variability of these white matter tract properties in various diffusion tensor imaging studies. The FADTTS integrates five statistical tools: (i) a multivariate varying coefficient model for allowing the varying coefficient functions in terms of arc length to characterize the varying associations between fiber bundle diffusion properties and a set of covariates, (ii) a weighted least squares estimation of the varying coefficient functions, (iii) a functional principal component analysis to delineate the structure of the variability in fiber bundle diffusion properties, (iv) a global test statistic to test hypotheses of interest, and (v) a simultaneous confidence band to quantify the uncertainty in the estimated coefficient functions. Simulated data are used to evaluate the finite sample performance of FADTTS. We apply FADTTS to investigate the development of white matter diffusivities along the splenium of the corpus callosum tract and the right internal capsule tract in a clinical study of neurodevelopment. FADTTS can be used to facilitate the understanding of normal brain development, the neural bases of neuropsychiatric disorders, and the joint effects of environmental and genetic factors on white matter fiber bundles. The advantages of FADTTS compared with the other existing approaches are that they are capable of modeling the structured inter-subject variability, testing the joint effects, and constructing their simultaneous confidence bands. However, FADTTS is not crucial for estimation and reduces to the functional analysis method for the single measure. Copyright © 2011 Elsevier Inc. All rights reserved.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

PubMed Central

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria.

PubMed

Kranz, Georg S; Seiger, Rene; Kaufmann, Ulrike; Hummer, Allan; Hahn, Andreas; Ganger, Sebastian; Tik, Martin; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

2017-04-15

Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are - at least in part - responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males. Copyright © 2017 Elsevier Inc. All rights reserved.

On describing human white matter anatomy: the white matter query language.

PubMed

Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2013-01-01

The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist's expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia.

Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

PubMed Central

Meoded, Avner; Kwan, Justin Y.; Peters, Tracy L.; Huey, Edward D.; Danielian, Laura E.; Wiggs, Edythe; Morrissette, Arthur; Wu, Tianxia; Russell, James W.; Bayat, Elham; Grafman, Jordan; Floeter, Mary Kay

2013-01-01

Introduction Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes. Methods The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI) and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment. PMID:24052798

Brain aging in humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta): magnetic resonance imaging studies of macro- and microstructural changes.

PubMed

Chen, Xu; Errangi, Bhargav; Li, Longchuan; Glasser, Matthew F; Westlye, Lars T; Fjell, Anders M; Walhovd, Kristine B; Hu, Xiaoping; Herndon, James G; Preuss, Todd M; Rilling, James K

2013-10-01

Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but this decrease occurred proportionally later in the chimpanzee lifespan than in humans. Diffusion MRI revealed widespread age-related decreases in fractional anisotropy and increases in radial diffusivity in chimpanzees and macaques. However, both the fractional anisotropy decline and the radial diffusivity increase started at a proportionally earlier age in humans than in chimpanzees. Thus, even though overall patterns of gray and white matter aging are similar in humans and chimpanzees, the longer lifespan of humans provides more time for white matter to deteriorate before death, with the result that some neurological effects of aging may be exacerbated in our species. Copyright © 2013 Elsevier Inc. All rights reserved.

Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease.

PubMed

Sun, Xiaoyan; Salat, David; Upchurch, Kristen; Deason, Rebecca; Kowall, Neil; Budson, Andrew

2014-10-01

Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.

White Matter Glia Pathology in Autism

DTIC Science & Technology

2013-09-01

www.ncbi.nlm.nih.gov/pubmed/21078227 5 . Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT , Chugani DC. Diffusion tensor imaging of frontal lobe in autism ...AD_________________ Award Number: W81XWH-12-1-0302 TITLE: White matter glia pathology in autism PRINCIPAL INVESTIGATOR...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE White matter glia pathology in autism 5a. CONTRACT NUMBER W81XWH-12-1-0302 5b

Language and Reading Skills in School-Aged Children and Adolescents Born Preterm Are Associated with White Matter Properties on Diffusion Tensor Imaging

ERIC Educational Resources Information Center

Feldman, Heidi M.; Lee, Eliana S.; Yeatman, Jason D.; Yeom, Kristen W.

2012-01-01

Children born preterm are at risk for deficits in language and reading. They are also at risk for injury to the white matter of the brain. The goal of this study was to determine whether performance in language and reading skills would be associated with white matter properties in children born preterm and full-term. Children born before 36 weeks…

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

White matter structure in loneliness: preliminary findings from diffusion tensor imaging.

PubMed

Tian, Yin; Liang, Shanshan; Yuan, Zhen; Chen, Sifan; Xu, Peng; Yao, Dezhong

2014-08-06

A pilot study was carried out to determine individual differences in perceived loneliness using diffusion tensor imaging. To the best of our knowledge, this is the first preliminary diffusion tensor imaging evidence that the ventral attention network, generally activated by attentional reorienting, was also related to loneliness. Image reconstruction results indicated significantly decreased fractional anisotropy of white matter fibers and that associated nodes of the ventral attention network are highly correlated with increased loneliness ratings. By providing evidence on the structural level, our findings suggested that attention-reorienting capabilities play an important role in shaping an individual's loneliness.

Neurite density index is sensitive to age related differences in the developing brain.

PubMed

Genc, Sila; Malpas, Charles B; Holland, Scott K; Beare, Richard; Silk, Timothy J

2017-03-01

White matter development during childhood and adolescence is characterised by increasing white matter coherence and organisation. Commonly used scalar metrics, such as fractional anisotropy (FA), are sensitive to multiple mechanisms of white matter change and therefore unable to distinguish between mechanisms that change during development. We investigate the relationship between age and neurite density index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the age-classification accuracy of NDI compared with FA, in a developmental cohort. Diffusion-weighted imaging data from 72 children and adolescents between the ages of 4-19 was collected (M=10.42, SD=3.99, 36 male). We compared NODDI metrics against conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) in terms of their relationship to age. An ROC analysis was also performed to assess the ability of each metric to classify older and younger participants. NDI exhibited a stronger relationship with age (median R 2 =.60) compared with MD (median R 2 =.39), FA (median R 2 =.27), AD (median R 2 =.14), and RD (median R 2 =.35) in a high proportion of white matter tracts. When participants were divided into an older and younger group, NDI achieved the best classification (median area under the curve [AUC]=.89), followed by MD (median AUC=.81), FA (median AUC=.80), RD (median AUC=.81), and AD (median AUC=.64). Our results demonstrate the sensitivity of NDI to age-related differences in white matter microstructural organisation over development. Importantly, NDI is more sensitive to such developmental changes compared to commonly used DTI metrics. This knowledge provides justification for implementing NODDI metrics in developmental studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

PubMed

Gramegna, L L; Pisano, A; Testa, C; Manners, D N; D'Angelo, R; Boschetti, E; Giancola, F; Pironi, L; Caporali, L; Capristo, M; Valentino, M L; Plazzi, G; Casali, C; Dotti, M T; Cenacchi, G; Hirano, M; Giordano, C; Parchi, P; Rinaldi, R; De Giorgio, R; Lodi, R; Carelli, V; Tonon, C

2018-01-18

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N -acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment. © 2018 by American Journal of Neuroradiology.

White matter integrity as a predictor of response to treatment in first episode psychosis.

PubMed

Reis Marques, Tiago; Taylor, Heather; Chaddock, Chris; Dell'acqua, Flavio; Handley, Rowena; Reinders, A A T Simone; Mondelli, Valeria; Bonaccorso, Stefania; Diforti, Marta; Simmons, Andrew; David, Anthony S; Murray, Robin M; Pariante, Carmine M; Kapur, Shitij; Dazzan, Paola

2014-01-01

The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response.

Neural connections foster social connections: a diffusion-weighted imaging study of social networks

PubMed Central

Hampton, William H.; Unger, Ashley; Von Der Heide, Rebecca J.

2016-01-01

Although we know the transition from childhood to adulthood is marked by important social and neural development, little is known about how social network size might affect neurocognitive development or vice versa. Neuroimaging research has identified several brain regions, such as the amygdala, as key to this affiliative behavior. However, white matter connectivity among these regions, and its behavioral correlates, remain unclear. Here we tested two hypotheses: that an amygdalocentric structural white matter network governs social affiliative behavior and that this network changes during adolescence and young adulthood. We measured social network size behaviorally, and white matter microstructure using probabilistic diffusion tensor imaging in a sample of neurologically normal adolescents and young adults. Our results suggest amygdala white matter microstructure is key to understanding individual differences in social network size, with connectivity to other social brain regions such as the orbitofrontal cortex and anterior temporal lobe predicting much variation. In addition, participant age correlated with both network size and white matter variation in this network. These findings suggest the transition to adulthood may constitute a critical period for the optimization of structural brain networks underlying affiliative behavior. PMID:26755769

Maternal adiposity negatively influences infant brain white matter development

USDA-ARS?s Scientific Manuscript database

Objective: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Methods: Diffusion tensor imaging was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age infants from uncomplicat...

White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

PubMed

Alfaro, Freddy J; Gavrieli, Anna; Saade-Lemus, Patricia; Lioutas, Vasileios-Arsenios; Upadhyay, Jagriti; Novak, Vera

2018-01-01

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

White matter correlates of cognitive domains in normal aging with diffusion tensor imaging.

PubMed

Sasson, Efrat; Doniger, Glen M; Pasternak, Ofer; Tarrasch, Ricardo; Assaf, Yaniv

2013-01-01

The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25-82 years), we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory) with white matter integrity, as measured by diffusion tensor imaging (DTI) fiber tracking in the temporal lobe projections [uncinate fasciculus (UF), fornix, cingulum, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF)]. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA) in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest (ROI) for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.

Usefulness of the apparent diffusion coefficient for the evaluation of the white matter to differentiate between glioblastoma and brain metastases.

PubMed

Miquelini, L A; Pérez Akly, M S; Funes, J A; Besada, C H

2016-01-01

To determine whether there are significant differences in the apparent diffusion coefficient (ADC) between the apparently normal peritumor white matter surrounding glioblastomas and that surrounding brain metastases. We retrospectively reviewed 42 patients with histologically confirmed glioblastomas and 42 patients with a single cerebral metastasis. We measured the signal intensity in the apparently normal peritumor white matter and in the abnormal peritumor white matter on the ADC maps. We used mean ADC values in the contralateral occipital white matter as a reference from which to design normalized ADC indices. We compared mean values between the two tumor types. We calculated the area under the receiver operator characteristic curve and estimated the sensitivity and specificity of the measurements taken. Supratentorial lesions and compromise of the corpus callosum were more common in patients with glioblastoma than in patients with brain metastases. The maximum diameter of the enhanced area after injection of a contrast agent was greater in the glioblastomas (p<0.001). The minimum ADC value measured in the apparently normal peritumor white matter was higher for the glioblastomas than for the metastases (p=0.002). Significant differences in the ADC index were found only for the minimum ADC value in apparently normal peritumor white matter. The sensitivity and specificity were less than 70% for all variables analyzed. There are differences in the ADC values of apparently normal peritumor white matter between glioblastomas and cerebral metastases, but the magnitude of these differences is slight and the application of these differences in clinical practice is still limited. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Framework for shape analysis of white matter fiber bundles.

PubMed

Glozman, Tanya; Bruckert, Lisa; Pestilli, Franco; Yecies, Derek W; Guibas, Leonidas J; Yeom, Kristen W

2018-02-15

Diffusion imaging coupled with tractography algorithms allows researchers to image human white matter fiber bundles in-vivo. These bundles are three-dimensional structures with shapes that change over time during the course of development as well as in pathologic states. While most studies on white matter variability focus on analysis of tissue properties estimated from the diffusion data, e.g. fractional anisotropy, the shape variability of white matter fiber bundle is much less explored. In this paper, we present a set of tools for shape analysis of white matter fiber bundles, namely: (1) a concise geometric model of bundle shapes; (2) a method for bundle registration between subjects; (3) a method for deformation estimation. Our framework is useful for analysis of shape variability in white matter fiber bundles. We demonstrate our framework by applying our methods on two datasets: one consisting of data for 6 normal adults and another consisting of data for 38 normal children of age 11 days to 8.5 years. We suggest a robust and reproducible method to measure changes in the shape of white matter fiber bundles. We demonstrate how this method can be used to create a model to assess age-dependent changes in the shape of specific fiber bundles. We derive such models for an ensemble of white matter fiber bundles on our pediatric dataset and show that our results agree with normative human head and brain growth data. Creating these models for a large pediatric longitudinal dataset may improve understanding of both normal development and pathologic states and propose novel parameters for the examination of the pediatric brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia.

PubMed

Rutten-Jacobs, Loes C A; Tozer, Daniel J; Duering, Marco; Malik, Rainer; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew

2018-06-01

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance ( VCAN [versican]: rs13164785; P =3.7×10 -18 for MD and rs67827860; P =1.3×10 -14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE, 0.15]; MD-WMHV rG 0.56 [SE, 0.19]). In polygenic risk score analysis, FA, MD, and WMHV were significantly associated with lacunar stroke, MD with major depressive disorder, and WMHV with Alzheimer disease. Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD. Mechanisms underlying white matter alterations are shared with cerebrovascular disease, and inherited differences in white matter microstructure impact on Alzheimer disease and major depressive disorder. © 2018 The Authors.

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy

PubMed Central

Loi, Richard Q.; Leyden, Kelly M.; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J.; Paul, Brianna M.; Dale, Anders M.; White, Nathan S.; McDonald, Carrie R.

2016-01-01

Objective Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI’s ability to separate intra-axonal diffusion (i.e., neurite density; ND) from diffusion associated with extra-axonal factors (e.g., inflammation; crossing fibers). Methods RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic hindered (IH) and free (IF) water, and crossing fibers (CF) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Results Reductions in FA were seen primarily in frontotemporal white matter in TLE and were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. Significance RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy. PMID:27735051

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy.

PubMed

Loi, Richard Q; Leyden, Kelly M; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J; Paul, Brianna M; Dale, Anders M; White, Nathan S; McDonald, Carrie R

2016-11-01

Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers). RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Reductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Altered white matter microstructure in adolescent substance users.

PubMed

Bava, Sunita; Frank, Lawrence R; McQueeny, Tim; Schweinsburg, Brian C; Schweinsburg, Alecia D; Tapert, Susan F

2009-09-30

Chronic marijuana use during adolescence is frequently comorbid with heavy alcohol consumption and associated with CNS alterations, yet the influence of early cannabis and alcohol use on microstructural white matter integrity is unclear. Building on evidence that cannabinoid receptors are present in myelin precursors and affect glial cell processing, and that excessive ethanol exposure is associated with persistently impaired myelination, we used diffusion tensor imaging (DTI) to characterize white matter integrity in heavy substance using and non-using adolescents. We evaluated 36 marijuana and alcohol-using (MJ+ALC) adolescents (ages 16-19) and 36 demographically similar non-using controls with DTI. The diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., Behrens, T.E., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505). MJ+ALC teens had significantly lower FA than controls in 10 regions, including left superior longitudinal fasciculus (SLF), left postcentral gyrus, bilateral crus cerebri, and inferior frontal and temporal white matter tracts. These diminutions occurred in the context of increased FA in right occipital, internal capsule, and SLF regions. Changes in MD were less distributed, but increased MD was evident in the right occipital lobe, whereas the left inferior longitudinal fasciculus showed lower MD in MJ+ALC users. Findings suggest that fronto-parietal circuitry may be particularly impacted in adolescent users of the most prevalent intoxicants: marijuana and alcohol. Disruptions to white matter in this young group could indicate aberrant axonal and myelin maturation with resultant compromise of fiber integrity. Findings of increased anisotropic diffusion in alternate brain regions suggest possible neuroadaptive processes and can be examined in future studies of connectivity to determine how aberrancies in specific tracts might influence efficient cognitive processing.

Analyses of Disruption of Cerebral White Matter Integrity in Schizophrenia with MR Diffusion Tensor Fiber Tracking Method

NASA Astrophysics Data System (ADS)

Yamamoto, Utako; Kobayashi, Tetsuo; Kito, Shinsuke; Koga, Yoshihiko

We have analyzed cerebral white matter using magnetic resonance diffusion tensor imaging (MR-DTI) to measure the diffusion anisotropy of water molecules. The goal of this study is the quantitative evaluation of schizophrenia. Diffusion tensor images are acquired for patients with schizophrenia and healthy comparison subjects, group-matched for age, sex, and handedness. Fiber tracking is performed on the superior longitudinal fasciculus for the comparison between the patient and comparison groups. We have analysed and compared the cross-sectional area on the starting coronal plane and the mean and standard deviation of the fractional anisotropy and the apparent diffusion coefficient along fibers in the right and left hemispheres. In the right hemisphere, the cross-sectional areas in patient group are significantly smaller than those in the comparison group. Furthermore, in the comparison group, the cross-sectional areas in the right hemisphere are significantly larger than those in the left hemisphere, whereas there is no significant difference in the patient group. These results suggest that we may evaluate the disruption in white matter integrity in schizophrenic patients quantitatively by comparing the cross-sectional area of the superior longitudinal fasciculus in the right and left hemispheres.

White matter integrity in dementia with Lewy bodies: A Voxel-Based Analysis of Diffusion Tensor Imaging

PubMed Central

Nedelska, Zuzana; Schwarz, Christopher G.; Boeve, Bradley F.; Lowe, Val; Reid, Robert I.; Przybelski, Scott A.; Lesnick, Timothy G.; Gunter, Jeffrey L.; Senjem, Matthew L.; Ferman, Tanis J.; Smith, Glenn E.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Kantarci, Kejal

2015-01-01

Many patients with dementia with Lewy bodies have overlapping Alzheimer's disease (AD)–related pathology, which may contribute to white matter (WM) diffusivity alterations on diffusion tensor imaging (DTI). Consecutive patients with DLB (n=30), age and sex matched AD patients (n=30), and cognitively normal controls (CN; n=60) were recruited. All subjects underwent DTI, 18F 2-fluoro-deoxy-d-glucose (FDG) and 11C Pittsburgh compound B (PiB) PET scans. DLB patients had reduced fractional anisotropy (FA) in the parieto-occipital WM but not elsewhere compared to CN, and elevated FA in parahippocampal WM compared to AD patients, which persisted after controlling for Aβ load in DLB. The pattern of WM FA alterations on DTI was consistent with the more diffuse posterior parietal and occipital glucose hypometabolism of FDG PET in the cortex. DLB is characterized by a loss of parieto-occipital WM integrity, independent of concomitant AD-related Aβ load. Cortical glucose hypometabolism accompanies WM FA alterations with a concordant pattern of gray and white matter involvement in the parieto-occipital lobes in DLB. PMID:25863527

Predictive classification of pediatric bipolar disorder using atlas-based diffusion weighted imaging and support vector machines.

PubMed

Mwangi, Benson; Wu, Mon-Ju; Bauer, Isabelle E; Modi, Haina; Zeni, Cristian P; Zunta-Soares, Giovana B; Hasan, Khader M; Soares, Jair C

2015-11-30

Previous studies have reported abnormalities of white-matter diffusivity in pediatric bipolar disorder. However, it has not been established whether these abnormalities are able to distinguish individual subjects with pediatric bipolar disorder from healthy controls with a high specificity and sensitivity. Diffusion-weighted imaging scans were acquired from 16 youths diagnosed with DSM-IV bipolar disorder and 16 demographically matched healthy controls. Regional white matter tissue microstructural measurements such as fractional anisotropy, axial diffusivity and radial diffusivity were computed using an atlas-based approach. These measurements were used to 'train' a support vector machine (SVM) algorithm to predict new or 'unseen' subjects' diagnostic labels. The SVM algorithm predicted individual subjects with specificity=87.5%, sensitivity=68.75%, accuracy=78.12%, positive predictive value=84.62%, negative predictive value=73.68%, area under receiver operating characteristic curve (AUROC)=0.7812 and chi-square p-value=0.0012. A pattern of reduced regional white matter fractional anisotropy was observed in pediatric bipolar disorder patients. These results suggest that atlas-based diffusion weighted imaging measurements can distinguish individual pediatric bipolar disorder patients from healthy controls. Notably, from a clinical perspective these findings will contribute to the pathophysiological understanding of pediatric bipolar disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anomalous White Matter Morphology in Adults Who Stutter

ERIC Educational Resources Information Center

Cieslak, Matthew; Ingham, Rojer J.; Ingham, Janis C.; Grafton, Scott T.

2015-01-01

Aims: Developmental stuttering is now generally considered to arise from genetic determinants interacting with neurologic function. Changes within speech-motor white matter (WM) connections may also be implicated. These connections can now be studied in great detail by high-angular-resolution diffusion magnetic resonance imaging. Therefore,…

White Matter Changes in Tinnitus: Is It All Age and Hearing Loss?

PubMed

Yoo, Hye Bin; De Ridder, Dirk; Vanneste, Sven

2016-02-01

Tinnitus is a condition characterized by the perception of auditory phantom sounds. It is known as the result of complex interactions between auditory and nonauditory regions. However, previous structural imaging studies on tinnitus patients showed evidence of significant white matter changes caused by hearing loss that are positively correlated with aging. Current study focused on which aspects of tinnitus pathologies affect the white matter integrity the most. We used the diffusion tensor imaging technique to acquire images that have higher contrast in brain white matter to analyze how white matter is influenced by tinnitus-related factors using voxel-based methods, region of interest analysis, and deterministic tractography. As a result, white matter integrity in chronic tinnitus patients was both directly affected by age and also mediated by the hearing loss. The most important changes in white matter regions were found bilaterally in the anterior corona radiata, anterior corpus callosum, and bilateral sagittal strata. In the tractography analysis, the white matter integrity values in tracts of right parahippocampus were correlated with the subjective tinnitus loudness.

White matter microstructure in athletes with a history of concussion: Comparing diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).

PubMed

Churchill, Nathan W; Caverzasi, Eduardo; Graham, Simon J; Hutchison, Michael G; Schweizer, Tom A

2017-08-01

Sport concussion is associated with disturbances in brain function in the absence of gross anatomical lesions, and may have long-term health consequences. Diffusion-weighted magnetic resonance imaging (MRI) methods provide a powerful tool for investigating alterations in white matter microstructure reflecting the long-term effects of concussion. In a previous study, diffusion tensor imaging (DTI) showed that athletes with a history of concussion had elevated fractional anisotropy (FA) and reduced mean diffusivity (MD) parameters. To better understand these effects, this study compared DTI results to neurite orientation dispersion and density imaging (NODDI), which was used to estimate the intracellular volume fraction (V IC ) and orientation dispersion index (ODI). Sixty-eight (68) varsity athletes were recruited, including 37 without a history of concussion and 31 with concussion >6 months prior to imaging. Univariate analyses showed elevated FA and decreased MD for concussed athletes, along with increased V IC and reduced ODI, indicating greater neurite density and coherence of neurite orientation within white matter. Multivariate analyses also showed that for athletes with a history of concussion, white matter regions with increased FA had increased V IC and decreased ODI, with greater effects among athletes who were imaged a longer time since their last concussion. These findings enhance our understanding of the relationship between the biophysics of water diffusion and concussion neurobiology for young, healthy adults. Hum Brain Mapp 38:4201-4211, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Compartment models of the diffusion MR signal in brain white matter: a taxonomy and comparison.

PubMed

Panagiotaki, Eleftheria; Schneider, Torben; Siow, Bernard; Hall, Matt G; Lythgoe, Mark F; Alexander, Daniel C

2012-02-01

This paper aims to identify the minimum requirements for an accurate model of the diffusion MR signal in white matter of the brain. We construct a taxonomy of multi-compartment models of white matter from combinations of simple models for the intra- and the extra-axonal spaces. We devise a new diffusion MRI protocol that provides measurements with a wide range of imaging parameters for diffusion sensitization both parallel and perpendicular to white matter fibres. We use the protocol to acquire data from two fixed rat brains, which allows us to fit, study and compare the different models. The study examines a total of 47 analytic models, including several well-used models from the literature, which we place within the taxonomy. The results show that models that incorporate intra-axonal restriction, such as ball and stick or CHARMED, generally explain the data better than those that do not, such as the DT or the biexponential models. However, three-compartment models which account for restriction parallel to the axons and incorporate pore size explain the measurements most accurately. The best fit comes from combining a full diffusion tensor (DT) model of the extra-axonal space with a cylindrical intra-axonal component of single radius and a third spherical compartment of non-zero radius. We also measure the stability of the non-zero radius intra-axonal models and find that single radius intra-axonal models are more stable than gamma distributed radii models with similar fitting performance. Copyright © 2011 Elsevier Inc. All rights reserved.

Cortical Gray and Adjacent White Matter Demonstrate Synchronous Maturation in Very Preterm Infants.

PubMed

Smyser, Tara A; Smyser, Christopher D; Rogers, Cynthia E; Gillespie, Sarah K; Inder, Terrie E; Neil, Jeffrey J

2016-08-01

Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer's disease.

PubMed

Ryan, Natalie S; Keihaninejad, Shiva; Shakespeare, Timothy J; Lehmann, Manja; Crutch, Sebastian J; Malone, Ian B; Thornton, John S; Mancini, Laura; Hyare, Harpreet; Yousry, Tarek; Ridgway, Gerard R; Zhang, Hui; Modat, Marc; Alexander, Daniel C; Rossor, Martin N; Ourselin, Sebastien; Fox, Nick C

2013-05-01

Amyloid imaging studies of presymptomatic familial Alzheimer's disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer's disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer's disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network.

Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.

PubMed

Wagner, Jan; Schoene-Bake, Jan-Christoph; Witt, Juri-Alexander; Helmstaedter, Christoph; Malter, Michael P; Stoecker, Winfried; Probst, Christian; Weber, Bernd; Elger, Christian E

2016-03-01

Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well. The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

PubMed

Kubicki, M; Baxi, M; Pasternak, O; Tang, Y; Karmacharya, S; Chunga, N; Lyall, A E; Rathi, Y; Eckbo, R; Bouix, S; Mortazavi, F; Papadimitriou, G; Shenton, M E; Westin, C F; Killiany, R; Makris, N; Rosene, D L

2018-04-26

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field.Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

White Matter Correlates of Auditory Comprehension Outcomes in Chronic Post-Stroke Aphasia

PubMed Central

Xing, Shihui; Lacey, Elizabeth H.; Skipper-Kallal, Laura M.; Zeng, Jinsheng; Turkeltaub, Peter E.

2017-01-01

Neuroimaging studies have shown that speech comprehension involves a number of widely distributed regions within the frontal and temporal lobes. We aimed to examine the differential contributions of white matter connectivity to auditory word and sentence comprehension in chronic post-stroke aphasia. Structural and diffusion MRI data were acquired on 40 patients with chronic post-stroke aphasia. A battery of auditory word and sentence comprehension tests were administered to all the patients. Tract-based spatial statistics were used to identify areas in which white matter integrity related to specific comprehension deficits. Relevant tracts were reconstructed using probabilistic tractography in healthy older participants, and the mean values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the entire tracts were examined in relation to comprehension scores. Anterior temporal white matter integrity loss and involvement of the uncinate fasciculus related to word-level comprehension deficits (RFA = 0.408, P = 0.012; RMD = −0.429, P = 0.008; RAD = −0.424, P = 0.009; RRD = −0.439, P = 0.007). Posterior temporal white matter integrity loss and involvement of the inferior longitudinal fasciculus related to sentence-level comprehension deficits (RFA = 0.382, P = 0.02; RMD = −0.461, P = 0.004; RAD = −0.457, P = 0.004; RRD = −0.453, P = 0.005). Loss of white matter integrity in the inferior fronto-occipital fasciculus related to both word- and sentence-level comprehension (word-level scores: RFA = 0.41, P = 0.012; RMD = −0.447, P = 0.006; RAD = −0.489, P = 0.002; RRD = −0.432, P = 0.008; sentence-level scores: RFA = 0.409, P = 0.012; RMD = −0.413, P = 0.011; RAD = −0.408, P = 0.012; RRD = −0.413, P = 0.011). Lesion overlap, but not white matter integrity, in the arcuate fasciculus related to sentence-level comprehension deficits. These findings suggest that word-level comprehension outcomes in chronic post-stroke aphasia rely primarily on anterior temporal lobe pathways, whereas sentence-level comprehension relies on more widespread pathways including the posterior temporal lobe. PMID:28275366

Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy.

PubMed

Thawani, Jayesh P; Singh, Nickpreet; Pisapia, Jared M; Abdullah, Kalil G; Parker, Drew; Pukenas, Bryan A; Zager, Eric L; Verma, Ragini; Brem, Steven

2017-04-01

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain. To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy. Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated white matter tracts in 3 dimensions using advanced diffusion tensor imaging techniques. This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcortical white matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution. Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology. Copyright © 2017 by the Congress of Neurological Surgeons

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

PubMed

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

2015-08-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

Inter-Parietal White Matter Development Predicts Numerical Performance in Young Children

ERIC Educational Resources Information Center

Cantlon, Jessica F.; Davis, Simon W.; Libertus, Melissa E.; Kahane, Jill; Brannon, Elizabeth M.; Pelphrey, Kevin A.

2011-01-01

In an effort to understand the role of interhemispheric transfer in numerical development, we investigated the relationship between children's developing knowledge of numbers and the integrity of their white matter connections between the cerebral hemispheres (the corpus callosum). We used diffusion tensor imaging (DTI) tractography analyses to…

White Matter Microstructure in Superior Longitudinal Fasciculus Associated with Spatial Working Memory Performance in Children

ERIC Educational Resources Information Center

Vestergaard, Martin; Madsen, Kathrine Skak; Baare, William F. C.; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

2011-01-01

During childhood and adolescence, ongoing white matter maturation in the fronto-parietal cortices and connecting fiber tracts is measurable with diffusion-weighted imaging. Important questions remain, however, about the links between these changes and developing cognitive functions. Spatial working memory (SWM) performance improves significantly…

White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

ERIC Educational Resources Information Center

Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

2011-01-01

White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

Time-to-Surgery and Pre-operative Cerebral Hemodynamics Predict Post-operative White Matter Injury in Neonates with Hypoplastic Left Heart Syndrome

PubMed Central

Lynch, Jennifer M.; Buckley, Erin M.; Schwab, Peter J.; McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Xiao, Rui; Goff, Donna A.; Nicolson, Susan C.; Montenegro, Lisa M.; Fuller, Stephanie; Gaynor, J. William; Spray, Thomas L.; Yodh, Arjun G.; Naim, Maryam Y.; Licht, Daniel J.

2014-01-01

Objective Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately half of the HLHS survivors exhibit neurobehavioral symptoms believed to be associated with this injury, though the exact timing of the injury is not known. Methods Neonates with HLHS were recruited for pre- and post-operative monitoring of cerebral oxygen saturation (ScO2), cerebral oxygen extraction fraction (OEF), and cerebral blood flow (CBF) using two non-invasive optical-based techniques, namely diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomical magnetic resonance imaging (MRI) scans were performed prior to and approximately one week after surgery in order to quantify the extent and timing of the acquired white matter injury. Risk factors for developing new or worsened white matter injury were assessed using uni- and multi-variate logistic regression. Results Thirty-seven neonates with HLHS were studied. In a univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time-to-surgery (p=0.0003). In a multivariate model, longer time between birth and surgery (i.e., time-to-surgery), delayed sternal closure, and higher pre-operative CBF were predictors of post-operative white matter injury. Additionally, longer time-to-surgery and higher pre-operative CBF on morning of surgery were correlated with lower ScO2 (p=0.03 and p=0.05) and higher OEF (p=0.05 and p=0.05). Conclusions Longer time-to-surgery is associated with new post-operative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation may decrease the likelihood of acquiring postoperative white matter injury. PMID:25109755

Analysis of the relationships between type 2 diabetes status, glycemic control, and neuroimaging measures in the Diabetes Heart Study Mind.

PubMed

Raffield, Laura M; Cox, Amanda J; Freedman, Barry I; Hugenschmidt, Christina E; Hsu, Fang-Chi; Wagner, Benjamin C; Xu, Jianzhao; Maldjian, Joseph A; Bowden, Donald W

2016-06-01

To examine the relationships between type 2 diabetes (T2D) status, glycemic control, and T2D duration with magnetic resonance imaging (MRI)-derived neuroimaging measures in European Americans from the Diabetes Heart Study (DHS) Mind cohort. Relationships were examined using marginal models with generalized estimating equations in 784 participants from 514 DHS Mind families. Fasting plasma glucose, glycated hemoglobin, and diabetes duration were analyzed in 682 participants with T2D. Models were adjusted for potential confounders, including age, sex, history of cardiovascular disease, smoking, educational attainment, and use of statins or blood pressure medications. Association was tested with gray and white matter volume, white matter lesion volume, gray matter cerebral blood flow, and white and gray matter fractional anisotropy and mean diffusivity. Adjusting for multiple comparisons, T2D status was associated with reduced white matter volume (p = 2.48 × 10(-6)) and reduced gray and white matter fractional anisotropy (p ≤ 0.001) in fully adjusted models, with a trend toward increased white matter lesion volume (p = 0.008) and increased gray and white matter mean diffusivity (p ≤ 0.031). Among T2D-affected participants, neither fasting glucose, glycated hemoglobin, nor diabetes duration were associated with the neuroimaging measures assessed (p > 0.05). While T2D was significantly associated with MRI-derived neuroimaging measures, differences in glycemic control in T2D-affected individuals in the DHS Mind study do not appear to significantly contribute to variation in these measures. This supports the idea that the presence or absence of T2D, not fine gradations of glycemic control, may be more significantly associated with age-related changes in the brain.

White matter connectivity and Internet gaming disorder

PubMed Central

Jeong, Bum Seok; Han, Doug Hyun; Kim, Sun Mi; Lee, Sang Won; Renshaw, Perry F.

2017-01-01

Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play. PMID:25899390

White matter integrity in alcohol-naive youth with a family history of alcohol use disorders

PubMed Central

Squeglia, L. M.; Jacobus, J.; Brumback, T.; Meloy, M. J.; Tapert, S. F.

2014-01-01

Background Understanding pre-existing neural vulnerabilities found in youth who are family history positive (FHP) for alcohol use disorders could help inform preventative interventions created to delay initiation age and escalation of heavy drinking. The goal of this study was to compare indices of white matter integrity using diffusion tensor imaging (DTI) between FHP and family history negative (FHN) youth using a sample of 94 alcohol-naive adolescents and to examine if differences were associated with global and domain-specific cognitive functioning. Method Participants were 48 FHP and 46 FHN demographically matched, healthy, substance-naive 12- to 14-year-olds (54% female) recruited from local middle schools. Participants completed a neuropsychological test battery and magnetic resonance imaging session, including DTI. Results FHP youth had higher fractional anisotropy and axial diffusivity, and lower radial and mean diffusivity, than FHN youth in 19 clusters spanning projection, association and interhemispheric white matter tracts. Findings were replicated after controlling for age, gender, socio-economic status, grade and pubertal development. Groups did not differ significantly on global or domain-specific neuropsychological test scores. Conclusions FHP teens showed higher white matter integrity, but similar cognitive functioning, to FHN youth. More mature neural features could be related to more precocious behaviors, such as substance use initiation, in FHP youth. Future research exploring white matter maturation before and after substance use initiation will help elucidate the neuro-developmental trajectories in youth at risk for substance use disorders, to inform preventive efforts and better understand the sequelae of adolescent alcohol and drug use. PMID:25066702

Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study.

PubMed

Cai, Suping; Jiang, Yuanyuan; Wang, Yubo; Wu, Xiaoming; Ren, Junchan; Lee, Min Seob; Lee, Sunghoon; Huang, Liyu

2017-03-30

Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer's disease. Previous neuroimaging studies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination

PubMed Central

Guglielmetti, C.; Veraart, J.; Roelant, E.; Mai, Z.; Daans, J.; Van Audekerke, J.; Naeyaert, M.; Vanhoutte, G.; Delgado y Palacios, R.; Praet, J.; Fieremans, E.; Ponsaerts, P.; Sijbers, J.; Van der Linden, A.; Verhoye, M.

2016-01-01

Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, MK, RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stage of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event. PMID:26525654

Alterations in White Matter Integrity in Young Adults with Smartphone Dependence

PubMed Central

Hu, Yuanming; Long, Xiaojing; Lyu, Hanqing; Zhou, Yangyang; Chen, Jianxiang

2017-01-01

Smartphone dependence (SPD) is increasingly regarded as a psychological problem, however, the underlying neural substrates of SPD is still not clear. High resolution magnetic resonance imaging provides a useful tool to help understand and manage the disorder. In this study, a tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) was used to measure white matter integrity in young adults with SPD. A total of 49 subjects were recruited and categorized into SPD and control group based on their clinical behavioral tests. To localize regions with abnormal white matter integrity in SPD, the voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on the whole brain was performed by TBSS. The correlation between the quantitative variables of brain structures and the behavior measures were performed. Our result demonstrated that SPD had significantly lower white matter integrity than controls in superior longitudinal fasciculus (SLF), superior corona radiata (SCR), internal capsule, external capsule, sagittal stratum, fornix/stria terminalis and midbrain structures. Correlation analysis showed that the observed abnormalities in internal capsule and stria terminalis were correlated with the severity of dependence and behavioral assessments. Our finding facilitated a primary understanding of white matter characteristics in SPD and indicated that the structural deficits might link to behavioral impairments. PMID:29163108

White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates.

PubMed

Tran, Linh T; Roos, Annerine; Fouche, Jean-Paul; Koen, Nastassja; Woods, Roger P; Zar, Heather J; Narr, Katherine L; Stein, Dan J; Donald, Kirsten A

2016-01-01

The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes.

Tract-based analysis of white matter integrity in psychotic and nonpsychotic bipolar disorder.

PubMed

Ji, Andrew; Godwin, Douglass; Rutlin, Jerrel; Kandala, Sridhar; Shimony, Joshua S; Mamah, Daniel

2017-02-01

At least 50% of individuals with bipolar disorder (BD) present with psychosis during their lifetime. Psychotic symptoms have sometimes been linked to specific genetic and phenotypic markers. This study aims to explore potential differences between bipolar disorder subtypes by measuring white matter integrity of the brain and relationships with clinical measures. Diffusion tensor imaging and clinical measures were acquired from 102 participants, grouped as psychotic bipolar disorder (PBD) (n=48), non-psychotic bipolar disorder (NBD) (n=24), and healthy controls (n=30). We utilized a powerful, automated tool (TRACULA: Tracts Constrained by Underlying Anatomy) to analyze the fractional anisotropy (FA) and mean diffusivity (MD) of 18 white matter tracts. Decreased FA in numerous tracts was observed in bipolar disorder groups compared to healthy controls: bilateral cingulum-cingulate gyrus bundles, corticospinal tracts, and superior longitudinal fasciculi as well as the right hemisphere cingulum-angular bundle. Only left uncinate fasciculus FA differed between PBD and NPBD groups. We found no group differences in MD. Positive symptoms correlated with FA in the superior (inversely) and inferior (directly) longitudinal fasciculi. Negative symptoms directly correlated with mean FA of the corticospinal tract and cingulum-angular bundle. Neurotropic, mood-stabilizing medication prescribed for individuals with BD may interact with measures of white matter integrity in our BD participants. Our results indicate decreased white matter coherence in BD. Minimal differences in white matter FA between PBD and NPBD participants suggest related underlying neurobiology. Copyright © 2016 Elsevier B.V. All rights reserved.

Developmental differences in white matter architecture between boys and girls.

PubMed

Schmithorst, Vincent J; Holland, Scott K; Dardzinski, Bernard J

2008-06-01

Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5-18 in a cross-sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito-parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex-age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. Copyright 2007 Wiley-Liss, Inc.

Diffusion tensor imaging of cingulum bundle and corpus callosum in schizophrenia vs. bipolar disorder.

PubMed

Nenadić, Igor; Hoof, Anna; Dietzek, Maren; Langbein, Kerstin; Reichenbach, Jürgen R; Sauer, Heinrich; Güllmar, Daniel

2017-08-30

Both schizophrenia and bipolar disorder show abnormalities of white matter, as seen in diffusion tensor imaging (DTI) analyses of major brain fibre bundles. While studies in each of the two conditions have indicated possible overlap in anatomical location, there are few direct comparisons between the disorders. Also, it is unclear whether phenotypically similar subgroups (e.g. patients with bipolar disorder and psychotic features) might share white matter pathologies or be rather similar. Using region-of-interest (ROI) analysis of white matter with diffusion tensor imaging (DTI) at 3 T, we analysed fractional anisotropy (FA), radial diffusivity (RD), and apparent diffusion coefficient (ADC) of the corpus callosum and cingulum bundle in 33 schizophrenia patients, 17 euthymic (previously psychotic) bipolar disorder patients, and 36 healthy controls. ANOVA analysis showed significant main effects of group for RD and ADC (both elevated in schizophrenia). Across the corpus callosum ROIs, there was not group effect on FA, but for RD (elevated in schizophrenia, lower in bipolar disorder) and ADC (higher in schizophrenia, intermediate in bipolar disorder). Our findings show similarities and difference (some gradual) across regions of the two major fibre tracts implicated in these disorders, which would be consistent with a neurobiological overlap of similar clinical phenotypes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Brain lesions in septic shock: a magnetic resonance imaging study.

PubMed

Sharshar, Tarek; Carlier, Robert; Bernard, Francis; Guidoux, Céline; Brouland, Jean-Philippe; Nardi, Olivier; de la Grandmaison, Geoffroy Lorin; Aboab, Jérôme; Gray, Françoise; Menon, David; Annane, Djillali

2007-05-01

Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock. Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61-79 years), SAPS II: 48 (44-56), SOFA: 8 (6-10)] underwent brain magnetic resonance imaging including gradient echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient. Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow-Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score. This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increased blood-brain barrier permeability, and were associated with poor outcome.

Occult White Matter Damage Contributes to Intellectual Disability in Tuberous Sclerosis Complex

ERIC Educational Resources Information Center

Yu, Chunshui; Lin, Fuchun; Zhao, Li; Ye, Jing; Qin, Wen

2009-01-01

Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of…

Clinical prediction of fall risk and white matter abnormalities: a diffusion tensor imaging study

USDA-ARS?s Scientific Manuscript database

The Tinetti scale is a simple clinical tool designed to predict risk of falling by focusing on gait and stance impairment in elderly persons. Gait impairment is also associated with white matter (WM) abnormalities. Objective: To test the hypothesis that elderly subjects at risk for falling, as deter...

Delay of gratification is associated with white matter connectivity in the dorsal prefrontal cortex: a diffusion tensor imaging study in chimpanzees (Pan troglodytes)

PubMed Central

Latzman, Robert D.; Taglialatela, Jared P.; Hopkins, William D.

2015-01-01

Individual variability in delay of gratification (DG) is associated with a number of important outcomes in both non-human and human primates. Using diffusion tensor imaging (DTI), this study describes the relationship between probabilistic estimates of white matter tracts projecting from the caudate to the prefrontal cortex (PFC) and DG abilities in a sample of 49 captive chimpanzees (Pan troglodytes). After accounting for time between collection of DTI scans and DG measurement, age and sex, higher white matter connectivity between the caudate and right dorsal PFC was found to be significantly associated with the acquisition (i.e. training phase) but not the maintenance of DG abilities. No other associations were found to be significant. The integrity of white matter connectivity between regions of the striatum and the PFC appear to be associated with inhibitory control in chimpanzees, with perturbations on this circuit potentially leading to a variety of maladaptive outcomes. Additionally, results have potential translational implications for understanding the pathophysiology of a number of psychiatric and clinical outcomes in humans. PMID:26041344

Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus macaques (Macaca mulatta)

PubMed Central

MO, Yin; CHAO, Fang; SONG, Ming; LIU, Ci-Rong; LIU, Hui-Lang; QIAN, Xi-Ying; ZHAO, Xu-Dong

2014-01-01

In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm2, spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm2, spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm2, spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm2, spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques. PMID:24866488

Global versus Tract-Specific Components of Cerebral White Matter Integrity: Relation to Adult Age and Perceptual-Motor Speed

PubMed Central

Johnson, Micah A.; Diaz, Michele T.; Madden, David J.

2014-01-01

Although age-related differences in white matter have been well documented, the degree to which regional, tract-specific effects can be distinguished from global, brain-general effects is not yet clear. Similarly, the manner in which global and regional differences in white matter integrity contribute to age-related differences in cognition has not been well established. To address these issues, we analyzed diffusion tensor imaging measures from 52 younger adults (18–28) and 64 older adults (60–85). We conducted principal component analysis on each diffusion measure, using data from eight individual tracts. Two components were observed for fractional anisotropy: The first comprised high loadings from the superior longitudinal fasciculi and corticospinal tracts, and the second comprised high loadings from the optic radiations. In contrast, variation in axial, radial, and mean diffusivities yielded a single-component solution in each case, with high loadings from most or all tracts. For fractional anisotropy, the complementary results of multiple components and variability in component loadings across tracts suggest regional variation. However, for the diffusivity indices, the single component with high loadings from most or all of the tracts suggests primarily global, brain-general variation. Further analyses indicated that age was a significant mediator of the relation between each component and perceptual-motor speed. These data suggest that individual differences in white matter integrity, and their relation to age-related differences in perceptual-motor speed, represent influences that are beyond the level of individual tracts, but the extent to which regional or global effects predominate may differ between anisotropy and diffusivity measures. PMID:24972959

White matter changes in an untreated, newly diagnosed case of classical homocystinuria.

PubMed

Brenton, J Nicholas; Matsumoto, Julie A; Rust, Robert S; Wilson, William G

2014-01-01

The authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diagnosis causing leukoencephalopathy, since classical homocystinuria is not typically associated with these changes. Other inborn errors of the transsulfuration pathway have been reported as causing these changes. Once begun on therapy for his homocystinuria, his neurologic deficits resolved and his delays rapidly improved. Repeat MRI performed one year after instating therapy showed resolution of his white matter abnormalities. This case illustrates the need to consider homocystinuria and other amino acidopathies in the differential diagnosis of childhood white matter diseases and lends weight to the hypothesis that hypermethioninemia may induce white matter changes.

Structure-Specific Statistical Mapping of White Matter Tracts

PubMed Central

Yushkevich, Paul A.; Zhang, Hui; Simon, Tony; Gee, James C.

2008-01-01

We present a new model-based framework for the statistical analysis of diffusion imaging data associated with specific white matter tracts. The framework takes advantage of the fact that several of the major white matter tracts are thin sheet-like structures that can be effectively modeled by medial representations. The approach involves segmenting major tracts and fitting them with deformable geometric medial models. The medial representation makes it possible to average and combine tensor-based features along directions locally perpendicular to the tracts, thus reducing data dimensionality and accounting for errors in normalization. The framework enables the analysis of individual white matter structures, and provides a range of possibilities for computing statistics and visualizing differences between cohorts. The framework is demonstrated in a study of white matter differences in pediatric chromosome 22q11.2 deletion syndrome. PMID:18407524

Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ.

PubMed

Mabbott, Donald J; Noseworthy, Michael D; Bouffet, Eric; Rockel, Conrad; Laughlin, Suzanne

2006-07-01

Treatment of children with cranial-spinal radiation (CSR) for brain tumors is associated with adverse intellectual outcome and white matter damage. However, the correlation between IQ and measures of white matter integrity has received little attention. We examined apparent diffusion coefficient (ADC), fractional anisotropy (FA), and intelligence in pediatric patients treated with CSR for medulloblastoma relative to control subjects. ADC and FA measures were obtained for eight patients and eight control children and evaluated in multiple regions of interest in the cerebral hemispheres. Mean ADC and mean FA for each region were calculated, group differences were evaluated, and the relationship between these measures and intelligence were examined. In our study group, decreased IQ was associated with increased ADC and decreased FA (P < 0.01). Mean IQ for the CSR group was lower than that for the control group, but the difference was not significant when controlling for overall mean FA or ADC (P > 0.10). Overall mean FA was lower and ADC was higher in the CSR group relative to controls (P < 0.01). Specifically, FA was lower in the genu of the corpus callosum, the anterior and posterior limbs of the internal capsule, inferior frontal white matter, and high frontal white matter, and ADC was higher in all regions in patients relative to controls (P < 0.01). Compromised white matter integrity was observed for multiple regions within the cerebral hemispheres following CSR. A novel finding was that microscopic damage in normal-appearing white matter, as indexed by higher ADC and lower FA, was related to poor intellectual outcome relative to age-matched controls.

Microstructural White Matter Alterations in the Corpus Callosum of Girls With Conduct Disorder.

PubMed

Menks, Willeke Martine; Furger, Reto; Lenz, Claudia; Fehlbaum, Lynn Valérie; Stadler, Christina; Raschle, Nora Maria

2017-03-01

Diffusion tensor imaging (DTI) studies in adolescent conduct disorder (CD) have demonstrated white matter alterations of tracts connecting functionally distinct fronto-limbic regions, but only in boys or mixed-gender samples. So far, no study has investigated white matter integrity in girls with CD on a whole-brain level. Therefore, our aim was to investigate white matter alterations in adolescent girls with CD. We collected high-resolution DTI data from 24 girls with CD and 20 typically developing control girls using a 3T magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed for whole-brain as well as a priori-defined regions of interest, while controlling for age and intelligence, using a voxel-based analysis and an age-appropriate customized template. Whole-brain findings revealed white matter alterations (i.e., increased FA) in girls with CD bilaterally within the body of the corpus callosum, expanding toward the right cingulum and left corona radiata. The FA and MD results in a priori-defined regions of interest were more widespread and included changes in the cingulum, corona radiata, fornix, and uncinate fasciculus. These results were not driven by age, intelligence, or attention-deficit/hyperactivity disorder comorbidity. This report provides the first evidence of white matter alterations in female adolescents with CD as indicated through white matter reductions in callosal tracts. This finding enhances current knowledge about the neuropathological basis of female CD. An increased understanding of gender-specific neuronal characteristics in CD may influence diagnosis, early detection, and successful intervention strategies. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

PubMed

Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

2017-11-15

Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

White-matter functional networks changes in patients with schizophrenia.

PubMed

Jiang, Yuchao; Luo, Cheng; Li, Xuan; Li, Yingjia; Yang, Hang; Li, Jianfu; Chang, Xin; Li, Hechun; Yang, Huanghao; Wang, Jijun; Duan, Mingjun; Yao, Dezhong

2018-04-13

Resting-state functional MRI (rsfMRI) is a useful technique for investigating the functional organization of human gray-matter in neuroscience and neuropsychiatry. Nevertheless, most studies have demonstrated the functional connectivity and/or task-related functional activity in the gray-matter. White-matter functional networks have been investigated in healthy subjects. Schizophrenia has been hypothesized to be a brain disorder involving insufficient or ineffective communication associated with white-matter abnormalities. However, previous studies have mainly examined the structural architecture of white-matter using MRI or diffusion tensor imaging and failed to uncover any dysfunctional connectivity within the white-matter on rsfMRI. The current study used rsfMRI to evaluate white-matter functional connectivity in a large cohort of ninety-seven schizophrenia patients and 126 healthy controls. Ten large-scale white-matter networks were identified by a cluster analysis of voxel-based white-matter functional connectivity and classified into superficial, middle and deep layers of networks. Evaluation of the spontaneous oscillation of white-matter networks and the functional connectivity between them showed that patients with schizophrenia had decreased amplitudes of low-frequency oscillation and increased functional connectivity in the superficial perception-motor networks. Additionally, we examined the interactions between white-matter and gray-matter networks. The superficial perception-motor white-matter network had decreased functional connectivity with the cortical perception-motor gray-matter networks. In contrast, the middle and deep white-matter networks had increased functional connectivity with the superficial perception-motor white-matter network and the cortical perception-motor gray-matter network. Thus, we presumed that the disrupted association between the gray-matter and white-matter networks in the perception-motor system may be compensated for through the middle-deep white-matter networks, which may be the foundation of the extensively disrupted connections in schizophrenia. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluating Kurtosis-based Diffusion MRI Tissue Models for White Matter with Fiber Ball Imaging

PubMed Central

Jensen, Jens H.; McKinnon, Emilie T.; Glenn, G. Russell; Helpern, Joseph A.

2018-01-01

In order to quantify well-defined microstructural properties of brain tissue from diffusion MRI (dMRI) data, tissue models are typically employed that relate biological features, such as cell morphology and cell membrane permeability, to the diffusion dynamics. A variety of such models have been proposed for white matter, and their validation is a topic of active interest. In this paper, three different tissue models are tested by comparing their predictions for a specific microstructural parameter to the value measured independently with a recently proposed dMRI method known as fiber ball imaging (FBI). The three tissue models are all constructed with the diffusion and kurtosis tensors, and they are hence compatible with diffusional kurtosis imaging (DKI). Nevertheless, the models differ significantly in their details and predictions. For voxels with fractional anisotropies (FA) exceeding 0.5, all three are reasonably consistent with FBI. However, for lower FA values, one of these, called the white matter tract integrity (WMTI) model, is found to be in much better accord with FBI than the other two, suggesting that the WMTI model has a broader range of applicability. PMID:28085211

Tractography of white matter based on diffusion tensor imaging in ischaemic stroke involving the corticospinal tract: a preliminary study

NASA Astrophysics Data System (ADS)

Zhong, Chongguang; Bai, Lijun; Cui, Fangyuan; Dai, Ruwei; Xue, Ting; Wang, Hu; Wei, Wenjuan; Liu, Zhenyu; You, Youbo; Zou, Yihuai; Tian, Jie

2012-03-01

Diffusion tensor MR imaging (DTI) provides information on diffusion anisotropy in vivo, which can be exhibited three-dimensional white matter tractography. Five healthy volunteers and five right-hand affected patients with early subacute ischaemic infarction involving the posterior limb of the internal capsule or corona radiate were recruited in this study. We used 3D white matter tractography to show the corticospinal tract in both volunteer group and stroke group. Then we compared parameters of the corticospinal tract in patients with that in normal subjects and assessed the relationships between the fiber number of the corticospinal tract in ipsilesional hemisphere and indicators of the patients' rehabilitation using Pearson correlation analysis. The fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) values in the ipsilesional corticospinal tract may significantly reduce comparing with the volunteer group. In addition, the stroke patient with less fiber number of the ipsilesional corticospinal tract may bear more possibilities of better motor rehabilitation. The FA values, ADC values and fiber number of the corticospinal tract in the ipsilesional hemisphere might be helpful to the prognosis and prediction of clinical treatment in stroke patients.

White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging.

PubMed

Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Davarani, Siamak Pn; Jiang, Quan

2017-01-01

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 10 6 , n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats. © The Author(s) 2015.

White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels.

PubMed

Molinuevo, José Luis; Ripolles, Pablo; Simó, Marta; Lladó, Albert; Olives, Jaume; Balasa, Mircea; Antonell, Anna; Rodriguez-Fornells, Antoni; Rami, Lorena

2014-12-01

The aim of this study was to use diffusion tensor imaging measures to determine the existence of white matter microstructural differences in the preclinical phases of Alzheimer's disease, assessing cognitively normal older individuals with positive amyloid β protein (Aβ42) levels (CN_Aβ42+) on the basis of normal cognition and cerebrospinal fluid Aβ42 levels below 500 pg/mL. Nineteen CN_Aβ42+ and 19 subjects with Aβ42 levels above 500 pg/mL (CN_Aβ42-) were included. We encountered increases in axial diffusivity (AxD) in CN_Aβ42+ relative to CN_Aβ42- in the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus, and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Cognitive reserve scores were positively associated with AxD exclusively in the CN_Aβ42+ group. The finding of AxD alteration together with preserved fractional anisotropy, mean diffusivity, and radial diffusivity indexes in the CN_Aβ42+ group may indicate that, subtle axonal changes may be happening in the preclinical phases of Alzheimer's disease, whereas white matter integrity is still widely preserved. Copyright © 2014 Elsevier Inc. All rights reserved.

White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging

PubMed Central

Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Davarani, Siamak PN

2015-01-01

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 106, n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats. PMID:26685128

Quantitative susceptibility mapping as a biomarker for evaluating white matter alterations in Parkinson's disease.

PubMed

Guan, Xiaojun; Huang, Peiyu; Zeng, Qiaoling; Liu, Chunlei; Wei, Hongjiang; Xuan, Min; Gu, Quanquan; Xu, Xiaojun; Wang, Nian; Yu, Xinfeng; Luo, Xiao; Zhang, Minming

2018-02-07

Myelinated white matter showing diamagnetic susceptibility is important for information transfer in the brain. In Parkinson's disease (PD), the white matter is also suffering degenerative alterations. Quantitative susceptibility mapping (QSM) is a novel technique for noninvasive assessment of regional white matter ultrastructure, and provides different information of white matter in addition to standard diffusion tensor imaging (DTI). In this study, we used QSM to detect spatial white matter alterations in PD patients (n = 65) and age- and sex-matched normal controls (n = 46). Voxel-wise tract-based spatial statistics were performed to analyze QSM and DTI data. QSM showed extensive white matter involvement-including regions adjacent to the frontal, parietal, and temporal lobes-in PD patients, which was more widespread than that observed using DTI. Both QSM and DTI showed similar alterations in the left inferior longitudinal fasciculus and right cerebellar hemisphere. Further, alterations in the white matter were correlated with motor impairment and global disease severity in PD patients. We suggest that QSM may provide a novel approach for detecting white matter alterations and underlying network disruptions in PD. Further, the combination of QSM and DTI would provide a more complete evaluation of the diseased brain by analyzing different biological tissue properties.

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson’s Disease: A Multimodal Imaging Study

PubMed Central

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Gómez-Beldarrain, María Ángeles; Gómez-Esteban, Juan Carlos; Ibarretxe-Bilbao, Naroa

2015-01-01

Background Parkinson’s disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions. Methods Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics. Results PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe. Conclusions Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships. PMID:26559669

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson's Disease: A Multimodal Imaging Study.

PubMed

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Gómez-Beldarrain, María Ángeles; Gómez-Esteban, Juan Carlos; Ibarretxe-Bilbao, Naroa

2015-01-01

Parkinson's disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions. Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics. PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe. Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships.

White-matter microstructure and hearing acuity in older adults: a population-based cross-sectional DTI study.

PubMed

Rigters, Stephanie C; Cremers, Lotte G M; Ikram, M Arfan; van der Schroeff, Marc P; de Groot, Marius; Roshchupkin, Gennady V; Niessen, Wiro J N; Baatenburg de Jong, Robert J; Goedegebure, André; Vernooij, Meike W

2018-01-01

To study the relation between the microstructure of white matter in the brain and hearing function in older adults we carried out a population-based, cross-sectional study. In 2562 participants of the Rotterdam Study, we conducted diffusion tensor imaging to determine the microstructure of the white-matter tracts. We performed pure-tone audiogram and digit-in-noise tests to quantify hearing acuity. Poorer white-matter microstructure, especially in the association tracts, was related to poorer hearing acuity. After differentiating the separate white-matter tracts in the left and right hemisphere, poorer white-matter microstructure in the right superior longitudinal fasciculus and the right uncinate fasciculus remained significantly associated with worse hearing. These associations did not significantly differ between middle-aged (51-69 years old) and older (70-100 years old) participants. Progressing age was thus not found to be an effect modifier. In a voxel-based analysis no voxels in the white matter were significantly associated with hearing impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Diffusion tensor imaging of the brainstem in children with achondroplasia

PubMed Central

BOSEMANI, THANGAMADHAN; ORMAN, GUNES; CARSON, KATHRYN A; MEODED, AVNER; HUISMAN, THIERRY A G M; PORETTI, ANDREA

2014-01-01

Aim The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Method Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Result Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo–15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo–14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. Interpretation The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients. PMID:24825324

Diffusion tensor imaging of the brainstem in children with achondroplasia.

PubMed

Bosemani, Thangamadhan; Orman, Gunes; Carson, Kathryn A; Meoded, Avner; Huisman, Thierry A G M; Poretti, Andrea

2014-11-01

The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients. © 2014 Mac Keith Press.

Diffusion Tensor Imaging of Pedophilia.

PubMed

Cantor, James M; Lafaille, Sophie; Soh, Debra W; Moayedi, Massieh; Mikulis, David J; Girard, Todd A

2015-11-01

Pedophilia is a principal motivator of child molestation, incurring great emotional and financial burdens on victims and society. Even among pedophiles who never commit any offense,the condition requires lifelong suppression and control. Previous comparison using voxel-based morphometry (VBM)of MR images from a large sample of pedophiles and controls revealed group differences in white matter. The present study therefore sought to verify and characterize white matter involvement using diffusion tensor imaging (DTI), which better captures the microstructure of white matter than does VBM. Pedophilics ex offenders (n=24) were compared with healthy, age-matched controls with no criminal record and no indication of pedophilia (n=32). White matter microstructure was analyzed with Tract-Based Spatial Statistics, and the trajectories of implicated fiber bundles were identified by probabilistic tractography. Groups showed significant, highly focused differences in DTI parameters which related to participants’ genital responses to sexual depictions of children, but not to measures of psychopathy or to childhood histories of physical abuse, sexual abuse, or neglect. Some previously reported gray matter differences were suggested under highly liberal statistical conditions (p(uncorrected)<.005), but did not survive ordinary statistical correction (whole brain per voxel false discovery rate of 5%). These results confirm that pedophilia is characterized by neuroanatomical differences in white matter microstructure, over and above any neural characteristics attributable to psychopathy and childhood adversity, which show neuroanatomic footprints of their own. Although some gray matter structures were implicated previously, only few have emerged reliably.

Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia

PubMed Central

Gilmore, John H.; Kang, Chaeryon; Evans, Dianne D.; Wolfe, Honor M.; Smith, J. Keith; Lieberman, Jeffrey A.; Lin, Weili; Hamer, Robert M.; Styner, Martin; Gerig, Guido

2011-01-01

Objective Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Method Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Results Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Conclusions Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia. PMID:20516153

Creatine, Glutamine plus Glutamate, and Macromolecules Are Decreased in the Central White Matter of Premature Neonates around Term

PubMed Central

Le Fur, Yann; Viout, Patrick; Ratiney, Hélène; Confort-Gouny, Sylviane; Cozzone, Patrick J.; Girard, Nadine

2016-01-01

Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (P<0.05), the occipital white matter (P<0.005) and the thalamus (P<0.05). The proton spectrum of the centrum semiovale was characterized by significantly lower taurine/H2O and macromolecules/H2O ratios (P<0.05) at a TE of 30 ms, and reduced (creatine+phosphocreatine)/H2O and (glutamine+glutamate)/H2O ratios (P<0.05) at a TE of 135 ms in the preterm neonates than in full-term neonates. Our findings indicate that premature neonates with normal conventional MRI present a delay in brain maturation affecting the white matter and the thalamus. Their brain metabolic profile is characterized by lower levels of creatine, glutamine plus glutamate, and macromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis. PMID:27547969

White matter integrity in individuals at ultra-high risk for psychosis: a systematic review and discussion of the role of polyunsaturated fatty acids.

PubMed

Vijayakumar, Nandita; Bartholomeusz, Cali; Whitford, Thomas; Hermens, Daniel F; Nelson, Barnaby; Rice, Simon; Whittle, Sarah; Pantelis, Christos; McGorry, Patrick; Schäfer, Miriam R; Amminger, G Paul

2016-08-11

Schizophrenia is thought to be a neurodevelopmental disorder with pathophysiological processes beginning in the brain prior to the emergence of clinical symptoms. Recent evidence from neuroimaging studies using techniques such as diffusion tensor imaging has identified white matter abnormalities that are suggestive of disrupted brain myelination and neuronal connectivity. Identifying whether such effects exist in individuals at high risk for developing psychosis may help with prevention and early intervention strategies. In addition, there is preliminary evidence for a role of lipid biology in the onset of psychosis, along with well-established evidence of its role in myelination of white matter tracts. As such, this article synthesises the literature on polyunsaturated fatty acids (PUFAs) in myelination and schizophrenia, hypothesizing that white matter abnormalities may potentially mediate the relationship between PUFAs and schizophrenia. Diffusion tensor imaging studies were identified through a systematic search of existing literature. Studies examined white matter integrity in ultra-high risk (UHR) samples, as assessed using structured diagnostic interviews. Data was extracted and summarised as a narrative review. Twelve studies met inclusion criteria, and findings identified reduced fractional anisotropy and higher diffusivity. Although the exact location of abnormalities remains uncertain, fronto-temporal and fronto-limbic connections, including the superior longitudinal and uncinate fasiculus, cingulum, and corpus callosum appear to be implicated. Because of preliminary evidence suggesting lipid biology may be relevant for the onset of psychosis, a discussion is provided of the role of polyunsaturated fatty acids (PUFAs) in myelination and risk for psychosis. While the function of PUFAs in myelination is well-established, there is growing evidence of reduced PUFA concentration in UHR samples, highlighting the need for research to examine the relationship between PUFA and white matter integrity in high-risk samples and age-matched healthy controls. Such investigations will help to better understand the pathophysiology of the disorder, and potentially assist in the development of novel treatment and early intervention strategies.

The grey matter correlates of impaired decision-making in multiple sclerosis

PubMed Central

Muhlert, Nils; Sethi, Varun; Cipolotti, Lisa; Haroon, Hamied; Parker, Geoff J M; Yousry, Tarek; Wheeler-Kingshott, Claudia; Miller, David; Ron, Maria; Chard, Declan

2015-01-01

Objective People with multiple sclerosis (MS) have difficulties with decision-making but it is unclear if this is due to changes in impulsivity, risk taking, deliberation or risk adjustment, and how this relates to brain pathology. Methods We assessed these aspects of decision-making in 105 people with MS and 43 healthy controls. We used a novel diffusion MRI method, diffusion orientational complexity (DOC), as an index of grey matter pathology in regions associated with decision-making and also measured grey matter tissue volumes and white matter lesion volumes. Results People with MS showed less adjustment to risk and slower decision-making than controls. Moreover, impaired decision-making correlated with reduced executive function, memory and processing speed. Decision-making impairments were most prevalent in people with secondary progressive MS. They were seen in patients with cognitive impairment and those without cognitive impairment. On diffusion MRI, people with MS showed DOC changes in all regions except the occipital cortex, relative to controls. Risk adjustment correlated with DOC in the hippocampi and deliberation time with DOC in the medial prefrontal, middle frontal gyrus, anterior cingulate and caudate parcellations and with white matter lesion volumes. Conclusions These data clarify the features of decision-making deficits in MS, and provide the first evidence that they relate to grey and white matter abnormalities seen using MRI. PMID:25006208

Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder.

PubMed

Landin-Romero, Ramón; Canales-Rodríguez, Erick J; Kumfor, Fiona; Moreno-Alcázar, Ana; Madre, Mercè; Maristany, Teresa; Pomarol-Clotet, Edith; Amann, Benedikt L

2017-01-01

The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.

Frontostriatal white matter integrity mediates adult age differences in probabilistic reward learning.

PubMed

Samanez-Larkin, Gregory R; Levens, Sara M; Perry, Lee M; Dougherty, Robert F; Knutson, Brian

2012-04-11

Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome

PubMed Central

Jalbrzikowski, Maria; Villalon-Reina, Julio E.; Karlsgodt, Katherine H.; Senturk, Damla; Chow, Carolyn; Thompson, Paul M.; Bearden, Carrie E.

2014-01-01

22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk. PMID:25426042

Fatigue and cognitive function in systemic lupus erythematosus: associations with white matter microstructural damage. A diffusion tensor MRI study and meta-analysis.

PubMed

Wiseman, S J; Bastin, M E; Hamilton, I F; Hunt, D; Ritchie, S J; Amft, E N; Thomson, S; Belch, J F F; Ralston, S H; Wardlaw, J M

2017-05-01

Objective The objective of this study was to investigate fatigue and cognitive impairments in systemic lupus erythematous (SLE) in relation to diffuse white matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate biomarkers of brain white matter microstructural integrity, was obtained in patients with SLE and age-matched controls. Fatigue and cognitive function were assessed and related to SLE activity, clinical data and plasma biomarkers of inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean age 48.8 ± 14.3 years) were included. Mean diffusivity (MD) was significantly higher in all white matter fibre tracts in SLE patients versus age-matched healthy controls ( p < 0.0001). Fatigue in SLE was higher than a normal reference range ( p < 0.0001) and associated with lower MD ( ß = -0.61, p = 0.02), depression ( ß = 0.17, p = 0.001), anxiety ( ß = 0.13, p = 0.006) and higher body mass index ( ß = 0.10, p = 0.004) in adjusted analyses. Poorer cognitive function was associated with longer SLE disease duration ( p = 0.003) and higher MD ( p = 0.03) and, in adjusted analysis, higher levels of IL-6 ( ß = -0.15, p = 0.02) but not with MD. Meta-analysis (10 studies, n = 261, including the present study) confirmed that patients with SLE have higher MD than controls. Conclusion Patients with SLE have more microstructural brain white matter damage for age than the general population, but this does not explain increased fatigue or lower cognition in SLE. The association between raised IL-6 and worse current cognitive function in SLE should be explored in larger datasets.

Brain intracellular metabolites are freely diffusing along cell fibers in grey and white matter, as measured by diffusion-weighted MR spectroscopy in the human brain at 7 T.

PubMed

Najac, Chloé; Branzoli, Francesca; Ronen, Itamar; Valette, Julien

2016-04-01

Due to the specific compartmentation of brain metabolites, diffusion-weighted magnetic resonance spectroscopy opens unique insight into neuronal and astrocytic microstructures. The apparent diffusion coefficient (ADC) of brain metabolites depends on various intracellular parameters including cytosol viscosity and molecular crowding. When diffusion time (t d) is long enough, the size and geometry of the compartment in which the metabolites diffuse strongly influence metabolites ADC. In a previous study, performed in the macaque brain, we measured neuronal and astrocytic metabolites ADC at long t d (from 86 to 1,011 ms) in a large voxel enclosing an equal proportion of white and grey matter. We showed that metabolites apparently diffuse freely along the axis of dendrites, axons and astrocytic processes. To assess potential differences between these two tissue types, here we measured for the first time in the Human brain the t d-dependency of metabolites trace/3 ADC at 7 teslas using a localized diffusion-weighted STEAM sequence, in parietal and occipital voxels, respectively, containing mainly white and grey matter. We show that, in both tissues and over the observed timescale (t d varying from 92 to 712 ms) metabolite ADC reaches a non-zero plateau, suggesting that metabolites are not confined inside subcellular regions such as cell bodies, or inside subcellular compartments such as organelles, but are rather free to diffuse in the whole fiber-like structure of neurons and astrocytes. Beyond the fundamental insights into intracellular compartmentation of metabolites, this work also provides a new framework for interpreting results of neuroimaging techniques based on molecular diffusion, such as diffusion-weighted magnetic resonance spectroscopy and imaging.

Brain intracellular metabolites are freely diffusing along cell fibers in grey and white matter, as measured by diffusion-weighted MR spectroscopy in the human brain at 7 T

PubMed Central

Najac, Chloé; Branzoli, Francesca; Ronen, Itamar; Valette, Julien

2016-01-01

Due to the specific compartmentation of brain metabolites, diffusion-weighted magnetic resonance spectroscopy opens unique insight into neuronal and astrocytic microstructures. The apparent diffusion coefficient (ADC) of brain metabolites depends on various intracellular parameters including cytosol viscosity and molecular crowding. When diffusion time (td) is long enough, the size and geometry of the compartment in which the metabolites diffuse strongly influence metabolites ADC. In a previous study, performed in the macaque brain, we measured neuronal and astrocytic metabolites ADC at long td (from 86 ms to 1011 ms) in a large voxel enclosing an equal proportion of white and grey matter. We showed that metabolites apparently diffuse freely along the axis of dendrites, axons and astrocytic processes. To assess potential differences between these two tissue types, here we measured for the first time in the Human brain the td-dependency of metabolites trace/3 ADC at 7 teslas using a localized diffusion-weighted STEAM sequence, in parietal and occipital voxels respectively containing mainly white and grey matter. We show that, in both tissues and over the observed timescale (td varying from 92 to 712 ms) metabolite ADC reaches a non-zero plateau, suggesting that metabolites are not confined inside subcellular regions such as cell bodies, or inside subcellular compartments such as organelles, but are rather free to diffuse in the whole fiber-like structure of neurons and astrocytes. Beyond the fundamental insights into intracellular compartmentation of metabolites, this work also provides a new framework for interpreting results of neuroimaging techniques based on molecular diffusion, such as diffusion-weighted magnetic resonance spectroscopy and imaging. PMID:25520054

A Sparse Bayesian Learning Algorithm for White Matter Parameter Estimation from Compressed Multi-shell Diffusion MRI.

PubMed

Pisharady, Pramod Kumar; Sotiropoulos, Stamatios N; Sapiro, Guillermo; Lenglet, Christophe

2017-09-01

We propose a sparse Bayesian learning algorithm for improved estimation of white matter fiber parameters from compressed (under-sampled q-space) multi-shell diffusion MRI data. The multi-shell data is represented in a dictionary form using a non-monoexponential decay model of diffusion, based on continuous gamma distribution of diffusivities. The fiber volume fractions with predefined orientations, which are the unknown parameters, form the dictionary weights. These unknown parameters are estimated with a linear un-mixing framework, using a sparse Bayesian learning algorithm. A localized learning of hyperparameters at each voxel and for each possible fiber orientations improves the parameter estimation. Our experiments using synthetic data from the ISBI 2012 HARDI reconstruction challenge and in-vivo data from the Human Connectome Project demonstrate the improvements.

Evaluation of cortical local field potential diffusion in stereotactic electro-encephalography recordings: A glimpse on white matter signal.

PubMed

Mercier, Manuel R; Bickel, Stephan; Megevand, Pierre; Groppe, David M; Schroeder, Charles E; Mehta, Ashesh D; Lado, Fred A

2017-02-15

While there is a strong interest in meso-scale field potential recording using intracranial electroencephalography with penetrating depth electrodes (i.e. stereotactic EEG or S-EEG) in humans, the signal recorded in the white matter remains ignored. White matter is generally considered electrically neutral and often included in the reference montage. Moreover, re-referencing electrophysiological data is a critical preprocessing choice that could drastically impact signal content and consequently the results of any given analysis. In the present stereotactic electroencephalography study, we first illustrate empirically the consequences of commonly used references (subdermal, white matter, global average, local montage) on inter-electrode signal correlation. Since most of these reference montages incorporate white matter signal, we next consider the difference between signals recorded in cortical gray matter and white matter. Our results reveal that electrode contacts located in the white matter record a mixture of activity, with part arising from the volume conduction (zero time delay) of activity from nearby gray matter. Furthermore, our analysis shows that white matter signal may be correlated with distant gray matter signal. While residual passive electrical spread from nearby matter may account for this relationship, our results suggest the possibility that this long distance correlation arises from the white matter fiber tracts themselves (i.e. activity from distant gray matter traveling along axonal fibers with time lag larger than zero); yet definitive conclusions about the origin of the white matter signal would require further experimental substantiation. By characterizing the properties of signals recorded in white matter and in gray matter, this study illustrates the importance of including anatomical prior knowledge when analyzing S-EEG data. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain white matter structure and COMT gene are linked to second-language learning in adults

PubMed Central

Mamiya, Ping C.; Richards, Todd L.; Coe, Bradley P.; Eichler, Evan E.; Kuhl, Patricia K.

2016-01-01

Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects’ grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype. PMID:27298360

Brain white matter structure and COMT gene are linked to second-language learning in adults.

PubMed

Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

2016-06-28

Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

Diffusion tensor imaging profiles reveal specific neural tract distortion in normal pressure hydrocephalus

PubMed Central

Pena, Alonso; Price, Stephen J.; Czosnyka, Marek; Czosnyka, Zofia; DeVito, Elise E.; Housden, Charlotte R.; Sahakian, Barbara J.; Pickard, John D.

2017-01-01

Background The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting. Methods Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients. We interrogated 40 datasets to generate a full panel of DTI measures and corroborated findings with plots of isotropy (p) vs. anisotropy (q). Results Concurrent examination of DTI measures revealed distinct profiles for NPH patients vs. controls. PQ plots demonstrated that patterns of injury occupied discrete white matter districts. DTI profiles for different white matter tracts showed changes consistent with i) predominant transependymal diffusion with stretch/ compression, ii) oedema with or without stretch/ compression and iii) predominant stretch/ compression. Findings were specific to individual tracts and dependent upon their proximity to the ventricles. At two weeks post-intervention, there was a 6·7% drop in axial diffusivity (p = 0·022) in the posterior limb of the internal capsule, compatible with improvement in stretch/ compression, that preceded any discernible changes in clinical outcome. On PQ plots, the trajectories of the posterior limb of the internal capsule and inferior longitudinal fasciculus suggested attempted ‘round trips’. i.e. return to normality. Conclusion DTI profiling with p:q correlation may offer a non-invasive biomarker of the characteristics of potentially reversible white matter injury. PMID:28817574

Diffusion tensor imaging profiles reveal specific neural tract distortion in normal pressure hydrocephalus.

PubMed

Keong, Nicole C; Pena, Alonso; Price, Stephen J; Czosnyka, Marek; Czosnyka, Zofia; DeVito, Elise E; Housden, Charlotte R; Sahakian, Barbara J; Pickard, John D

2017-01-01

The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting. Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients. We interrogated 40 datasets to generate a full panel of DTI measures and corroborated findings with plots of isotropy (p) vs. anisotropy (q). Concurrent examination of DTI measures revealed distinct profiles for NPH patients vs. controls. PQ plots demonstrated that patterns of injury occupied discrete white matter districts. DTI profiles for different white matter tracts showed changes consistent with i) predominant transependymal diffusion with stretch/ compression, ii) oedema with or without stretch/ compression and iii) predominant stretch/ compression. Findings were specific to individual tracts and dependent upon their proximity to the ventricles. At two weeks post-intervention, there was a 6·7% drop in axial diffusivity (p = 0·022) in the posterior limb of the internal capsule, compatible with improvement in stretch/ compression, that preceded any discernible changes in clinical outcome. On PQ plots, the trajectories of the posterior limb of the internal capsule and inferior longitudinal fasciculus suggested attempted 'round trips'. i.e. return to normality. DTI profiling with p:q correlation may offer a non-invasive biomarker of the characteristics of potentially reversible white matter injury.

Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease

PubMed Central

Keihaninejad, Shiva; Shakespeare, Timothy J.; Lehmann, Manja; Crutch, Sebastian J.; Malone, Ian B.; Thornton, John S.; Mancini, Laura; Hyare, Harpreet; Yousry, Tarek; Ridgway, Gerard R.; Zhang, Hui; Modat, Marc; Alexander, Daniel C.; Rossor, Martin N.; Ourselin, Sebastien; Fox, Nick C.

2013-01-01

Amyloid imaging studies of presymptomatic familial Alzheimer’s disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer’s disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer’s disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network. PMID:23539189

Manual dexterity and brain structure in patients with schizophrenia: A whole-brain magnetic resonance imaging study.

PubMed

Hidese, Shinsuke; Ota, Miho; Sasayama, Daimei; Matsuo, Junko; Ishida, Ikki; Hiraishi, Moeko; Teraishi, Toshiya; Hattori, Kotaro; Kunugi, Hiroshi

2018-04-14

The Purdue Pegboard Test (PPT) is a motor coordination task used to assess manual dexterity. Although several brain regions are thought to be involved in PPT performance, the relationship of the task with decreased insular volume has not been investigated. The PPT was administered to 83 subjects diagnosed with schizophrenia (mean ± standard deviation age: 38.6 ± 11.2 years; 47 males, 36 females) and 130 healthy controls (42.1 ± 15.2 years; 67 males, 63 females). All subjects were Japanese and right-handed. Gray matter volume was analyzed using voxel-based morphometry in statistical parametric mapping, while white matter measures were analyzed using diffusion tensor imaging in tract-based spatial statistics. For the patients with schizophrenia, the left-hand scores positively correlated with the right insular and bilateral operculum volumes, while the summation score (sum of left-, right-, and both-hands scores) positively correlated with the right insular volume, and the summation and assembly (number of assemblies completed) scores correlated with the diffuse white matter fractional anisotropy, axial diffusivity, and radial diffusivity values. In contrast, no significant correlations were found for the controls. These results suggested that decreased insular volume and white matter measures contributed to the impairments in manual dexterity observed in subjects with schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Widespread White Matter Differences in Children and Adolescents with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Vogan, V. M.; Morgan, B. R.; Leung, R. C.; Anagnostou, E.; Doyle-Thomas, K.; Taylor, M. J.

2016-01-01

Diffusion tensor imaging studies show white matter (WM) abnormalities in children with autism spectrum disorder (ASD). However, investigations are often limited by small samples, particularly problematic given the heterogeneity of ASD. We explored WM using DTI in a large sample of 130 children and adolescents (7-15 years) with and without ASD,…

Central Nervous System Brucellosis Granuloma and White Matter Disease in Immunocompromised Patient.

PubMed

Alqwaifly, Mohammed; Al-Ajlan, Fahad S; Al-Hindi, Hindi; Al Semari, Abdulaziz

2017-06-01

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen.

The Structural Plasticity of White Matter Networks Following Anterior Temporal Lobe Resection

ERIC Educational Resources Information Center

Yogarajah, Mahinda; Focke, Niels K.; Bonelli, Silvia B.; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W.; Alexander, Daniel C.; Symms, Mark R.; Koepp, Matthias J.; Duncan, John S.

2010-01-01

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy…

White Matter and Development in Children with an Autism Spectrum Disorder

ERIC Educational Resources Information Center

Mak-Fan, Kathleen M.; Morris, Drew; Vidal, Julie; Anagnostou, Evdokia; Roberts, Wendy; Taylor, Margot J.

2013-01-01

Recent research suggests that brain development follows an abnormal trajectory in children with autism spectrum disorders (ASD). The current study examined changes in diffusivity with age within defined white matter tracts in a group of typically developing children and a group of children with an ASD, aged 6 to 14 years. Age by group interactions…

White Matter Microstructure of the Human Mirror Neuron System Is Related to Symptom Severity in Adults with Autism

ERIC Educational Resources Information Center

Fründt, Odette; Schulz, Robert; Schöttle, Daniel; Cheng, Bastian; Thomalla, Götz; Braaß, Hanna; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K.; Bäumer, Tobias; Münchau, Alexander

2018-01-01

Mirror neuron system (MNS) dysfunctions might underlie deficits in autism spectrum disorders (ASD). Diffusion tensor imaging based probabilistic tractography was conducted in 15 adult ASD patients and 13 matched, healthy controls. Fractional anisotropy (FA) was quantified to assess group differences in tract-related white matter microstructure of…

Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome

ERIC Educational Resources Information Center

Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.

2009-01-01

Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…

Long-Term Cognitive and Behavioral Therapies, Combined with Augmentative Communication, Are Related to Uncinate Fasciculus Integrity in Autism

ERIC Educational Resources Information Center

Pardini, Matteo; Elia, Maurizio; Garaci, Francesco G.; Guida, Silvia; Coniglione, Filadelfo; Krueger, Frank; Benassi, Francesca; Gialloreti, Leonardo Emberti

2012-01-01

Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive…

Apparent diffusion coefficient of the normal human brain for various experimental conditions

NASA Astrophysics Data System (ADS)

Moraru, Luminita; Dimitrievici, Lucian

2017-01-01

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) is being increasingly used to assess both brain tissues and cerebrospinal fluid integrity. In this paper we study inter-site reproducibility of the apparent diffusion coefficient values for the main cerebral tissues such as gray matter, white matter and into cerebrospinal fluid and for three different stacks of slices that were spaced at L = 79.8, 84.9 and 90 mm. We assessed the impact of the attenuation factor and diffusion gradient on the results reproducibility.

Alteration in the number and integrity of white matter tracts in the preterm: A quantitative diffusion tensor imaging and diffusion fibre tractography in children

PubMed Central

Sreedharan, Ruma M; Aiyappan, Subramonium; Roy, N

2017-01-01

Purpose: Periventricular white matter is most commonly injured in preterm babies with hypoxia. To assess white matter damage, we decided to perform diffusion tensor imaging (DTI) in preterm children with history of hypoxia and magnetic resonance imaging (MRI) features of periventricular leukomalacia (PVL) (PTH). We hypothesized that the PTH have reduced number of white matter fibres compared to age matched pre term children without hypoxia (PTHO), and also depending on the severity of PVL, there could be reduction in the number of fibres as well. Materials and Methods: The present study was carried out at the Government Medical College, Thiruvananthapuram. DTI was performed on 15 PTH and 15 PTHO. We measured number of fibres and fractional anisotropy of corpus callosum (CC) and optic radiations (OR). Results: There was significant difference between two groups with regard OR (P < 0.001). The mean number of OR fibres in cases and control was 104 ± 28.44 (mean ± SD) and 578 ± 286 (mean ± SD), respectively. The mean number of CC in cases was 953 ± 429 and in controls was 1625 ± 116 with a P value <0.56. No significant difference in FA was seen between cases and controls (P = 0.94). Conclusions: Preterm children with history of hypoxia and MRI features of PVL show reduced number of CC and OR compared to preterm children without hypoxia. There was significant correlation between PVL severity and number of OR fibres which could be due to the preferential involvement of periventricular white matter, in which OR has a major contribution. PMID:28744069

Left hemisphere fractional anisotropy increase in noise-induced tinnitus: a diffusion tensor imaging (DTI) study of white matter tracts in the brain.

PubMed

Benson, Randall R; Gattu, Ramtilak; Cacace, Anthony T

2014-03-01

Diffusion tensor imaging (DTI) is a contemporary neuroimaging modality used to study connectivity patterns and microstructure of white matter tracts in the brain. The use of DTI in the study of tinnitus is a relatively unexplored methodology with no studies focusing specifically on tinnitus induced by noise exposure. In this investigation, participants were two groups of adults matched for etiology, age, and degree of peripheral hearing loss, but differed by the presence or absence (+/-) of tinnitus. It is assumed that matching individuals on the basis of peripheral hearing loss, allows for differentiating changes in white matter microstructure due to hearing loss from changes due to the effects of chronic tinnitus. Alterations in white matter tracts, using the fractional anisotropy (FA) metric, which measures directional diffusion of water, were quantified using tract-based spatial statistics (TBSS) with additional details provided by in vivo probabilistic tractography. Our results indicate that 10 voxel clusters differentiated the two groups, including 9 with higher FA in the group with tinnitus. A decrease in FA was found for a single cluster in the group with tinnitus. However, seven of the 9 clusters with higher FA were in left hemisphere thalamic, frontal, and parietal white matter. These foci were localized to the anterior thalamic radiations and the inferior and superior longitudinal fasciculi. The two right-sided clusters with increased FA were located in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus. The only decrease in FA for the tinnitus-positive group was found in the superior longitudinal fasciculus of the left parietal lobe. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of bilingualism on white matter integrity in older adults.

PubMed

Anderson, John A E; Grundy, John G; De Frutos, Jaisalmer; Barker, Ryan M; Grady, Cheryl; Bialystok, Ellen

2018-02-15

Bilingualism can delay the onset of dementia symptoms and has thus been characterized as a mechanism for cognitive or brain reserve, although the origin of this reserve is unknown. Studies with young adults generally show that bilingualism is associated with a strengthening of white matter, but there is conflicting evidence for how bilingualism affects white matter in older age. Given that bilingualism has been shown to help stave off the symptoms of dementia by up to four years, it is crucial that we clarify the mechanism underlying this reserve. The current study uses diffusion tensor imaging (DTI) to compare monolinguals and bilinguals while carefully controlling for potential confounds (e.g., I.Q., MMSE, and demographic variables). We show that group differences in Fractional Anisotropy (FA) and Radial Diffusivity (RD) arise from multivariable interactions not adequately controlled for by sequential bivariate testing. After matching and statistically controlling for confounds, bilinguals still had greater axial diffusivity (AD) in the left superior longitudinal fasciculus than monolingual peers, supporting a neural reserve account for healthy older bilinguals. Copyright © 2017 Elsevier Inc. All rights reserved.

Detection of white matter injury in concussion using high-definition fiber tractography.

PubMed

Shin, Samuel S; Pathak, Sudhir; Presson, Nora; Bird, William; Wagener, Lauren; Schneider, Walter; Okonkwo, David O; Fernandez-Miranda, Juan C

2014-01-01

Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients. © 2014 S. Karger AG, Basel.

White matter microstructure throughout the brain correlates with visual imagery in grapheme-color synesthesia.

PubMed

Whitaker, Kirstie J; Kang, Xiaojian; Herron, Timothy J; Woods, David L; Robertson, Lynn C; Alvarez, Bryan D

2014-04-15

In this study we show, for the first time, a correlation between the neuroanatomy of the synesthetic brain and a metric that measures behavior not exclusive to the synesthetic experience. Grapheme-color synesthetes (n=20), who experience colors triggered by viewing or thinking of specific letters or numbers, showed altered white matter microstructure, as measured using diffusion tensor imaging, compared with carefully matched non-synesthetic controls. Synesthetes had lower fractional anisotropy and higher perpendicular diffusivity when compared to non-synesthetic controls. An analysis of the mode of anisotropy suggested that these differences were likely due to the presence of more crossing pathways in the brains of synesthetes. Additionally, these differences in white matter microstructure correlated negatively, and only for synesthetes, with a measure of the vividness of their visual imagery. Synesthetes who reported the most vivid visual imagery had the lowest fractional anisotropy and highest perpendicular diffusivity. We conclude that synesthetes as a population vary along a continuum while showing categorical differences in neuroanatomy and behavior compared to non-synesthetes. Copyright © 2013 Elsevier Inc. All rights reserved.

Cerebrovascular reactivity and white matter integrity.

PubMed

Sam, Kevin; Peltenburg, Boris; Conklin, John; Sobczyk, Olivia; Poublanc, Julien; Crawley, Adrian P; Mandell, Daniel M; Venkatraghavan, Lakshmikumar; Duffin, James; Fisher, Joseph A; Black, Sandra E; Mikulis, David J

2016-11-29

To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR). Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons. Areas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p < 0.01), compared to areas with positive CVR. Impaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease. © 2016 American Academy of Neurology.

Functionally defined white matter reveals segregated pathways in human ventral temporal cortex associated with category-specific processing

PubMed Central

Gomez, Jesse; Pestilli, Franco; Witthoft, Nathan; Golarai, Golijeh; Liberman, Alina; Poltoratski, Sonia; Yoon, Jennifer; Grill-Spector, Kalanit

2014-01-01

Summary It is unknown if the white matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

Multivariate statistical analysis of diffusion imaging parameters using partial least squares: Application to white matter variations in Alzheimer's disease.

PubMed

Konukoglu, Ender; Coutu, Jean-Philippe; Salat, David H; Fischl, Bruce

2016-07-01

Diffusion magnetic resonance imaging (dMRI) is a unique technology that allows the noninvasive quantification of microstructural tissue properties of the human brain in healthy subjects as well as the probing of disease-induced variations. Population studies of dMRI data have been essential in identifying pathological structural changes in various conditions, such as Alzheimer's and Huntington's diseases (Salat et al., 2010; Rosas et al., 2006). The most common form of dMRI involves fitting a tensor to the underlying imaging data (known as diffusion tensor imaging, or DTI), then deriving parametric maps, each quantifying a different aspect of the underlying microstructure, e.g. fractional anisotropy and mean diffusivity. To date, the statistical methods utilized in most DTI population studies either analyzed only one such map or analyzed several of them, each in isolation. However, it is most likely that variations in the microstructure due to pathology or normal variability would affect several parameters simultaneously, with differing variations modulating the various parameters to differing degrees. Therefore, joint analysis of the available diffusion maps can be more powerful in characterizing histopathology and distinguishing between conditions than the widely used univariate analysis. In this article, we propose a multivariate approach for statistical analysis of diffusion parameters that uses partial least squares correlation (PLSC) analysis and permutation testing as building blocks in a voxel-wise fashion. Stemming from the common formulation, we present three different multivariate procedures for group analysis, regressing-out nuisance parameters and comparing effects of different conditions. We used the proposed procedures to study the effects of non-demented aging, Alzheimer's disease and mild cognitive impairment on the white matter. Here, we present results demonstrating that the proposed PLSC-based approach can differentiate between effects of different conditions in the same region as well as uncover spatial variations of effects across the white matter. The proposed procedures were able to answer questions on structural variations such as: "are there regions in the white matter where Alzheimer's disease has a different effect than aging or similar effect as aging?" and "are there regions in the white matter that are affected by both mild cognitive impairment and Alzheimer's disease but with differing multivariate effects?" Copyright © 2016 Elsevier Inc. All rights reserved.

Multivariate Statistical Analysis of Diffusion Imaging Parameters using Partial Least Squares: Application to White Matter Variations in Alzheimer’s Disease

PubMed Central

Konukoglu, Ender; Coutu, Jean-Philippe; Salat, David H.; Fischl, Bruce

2016-01-01

Diffusion magnetic resonance imaging (dMRI) is a unique technology that allows the noninvasive quantification of microstructural tissue properties of the human brain in healthy subjects as well as the probing of disease-induced variations. Population studies of dMRI data have been essential in identifying pathological structural changes in various conditions, such as Alzheimer’s and Huntington’s diseases1,2. The most common form of dMRI involves fitting a tensor to the underlying imaging data (known as Diffusion Tensor Imaging, or DTI), then deriving parametric maps, each quantifying a different aspect of the underlying microstructure, e.g. fractional anisotropy and mean diffusivity. To date, the statistical methods utilized in most DTI population studies either analyzed only one such map or analyzed several of them, each in isolation. However, it is most likely that variations in the microstructure due to pathology or normal variability would affect several parameters simultaneously, with differing variations modulating the various parameters to differing degrees. Therefore, joint analysis of the available diffusion maps can be more powerful in characterizing histopathology and distinguishing between conditions than the widely used univariate analysis. In this article, we propose a multivariate approach for statistical analysis of diffusion parameters that uses partial least squares correlation (PLSC) analysis and permutation testing as building blocks in a voxel-wise fashion. Stemming from the common formulation, we present three different multivariate procedures for group analysis, regressing-out nuisance parameters and comparing effects of different conditions. We used the proposed procedures to study the effects of non-demented aging, Alzheimer’s disease and mild cognitive impairment on the white matter. Here, we present results demonstrating that the proposed PLSC-based approach can differentiate between effects of different conditions in the same region as well as uncover spatial variations of effects across the white matter. The proposed procedures were able to answer questions on structural variations such as: “are there regions in the white matter where Alzheimer’s disease has a different effect than aging or similar effect as aging?” and “are there regions in the white matter that are affected by both mild cognitive impairment and Alzheimer’s disease but with differing multivariate effects?” PMID:27103138

Visual White Matter Integrity in Schizophrenia

PubMed Central

Butler, Pamela D.; Hoptman, Matthew J.; Nierenberg, Jay; Foxe, John J.; Javitt, Daniel C.; Lim, Kelvin O.

2007-01-01

Objective Patients with schizophrenia have visual-processing deficits. This study examines visual white matter integrity as a potential mechanism for these deficits. Method Diffusion tensor imaging was used to examine white matter integrity at four levels of the visual system in 17 patients with schizophrenia and 21 comparison subjects. The levels examined were the optic radiations, the striate cortex, the inferior parietal lobule, and the fusiform gyrus. Results Schizophrenia patients showed a significant decrease in fractional anisotropy in the optic radiations but not in any other region. Conclusions This finding indicates that white matter integrity is more impaired at initial input, rather than at higher levels of the visual system, and supports the hypothesis that visual-processing deficits occur at the early stages of processing. PMID:17074957

White matter damage is related to ataxia severity in SCA3.

PubMed

Kang, J-S; Klein, J C; Baudrexel, S; Deichmann, R; Nolte, D; Hilker, R

2014-02-01

Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

Probabilistic atlases of default mode, executive control and salience network white matter tracts: an fMRI-guided diffusion tensor imaging and tractography study

PubMed Central

Figley, Teresa D.; Bhullar, Navdeep; Courtney, Susan M.; Figley, Chase R.

2015-01-01

Diffusion tensor imaging (DTI) is a powerful MRI technique that can be used to estimate both the microstructural integrity and the trajectories of white matter pathways throughout the central nervous system. This fiber tracking (aka, “tractography”) approach is often carried out using anatomically-defined seed points to identify white matter tracts that pass through one or more structures, but can also be performed using functionally-defined regions of interest (ROIs) that have been determined using functional MRI (fMRI) or other methods. In this study, we performed fMRI-guided DTI tractography between all of the previously defined nodes within each of six common resting-state brain networks, including the: dorsal Default Mode Network (dDMN), ventral Default Mode Network (vDMN), left Executive Control Network (lECN), right Executive Control Network (rECN), anterior Salience Network (aSN), and posterior Salience Network (pSN). By normalizing the data from 32 healthy control subjects to a standard template—using high-dimensional, non-linear warping methods—we were able to create probabilistic white matter atlases for each tract in stereotaxic coordinates. By investigating all 198 ROI-to-ROI combinations within the aforementioned resting-state networks (for a total of 6336 independent DTI tractography analyses), the resulting probabilistic atlases represent a comprehensive cohort of functionally-defined white matter regions that can be used in future brain imaging studies to: (1) ascribe DTI or other white matter changes to particular functional brain networks, and (2) compliment resting state fMRI or other functional connectivity analyses. PMID:26578930

White Matter Integrity Reductions in Intermittent Explosive Disorder

PubMed Central

Lee, Royce; Arfanakis, Konstantinos; Evia, Arnold M; Fanning, Jennifer; Keedy, Sarah; Coccaro, Emil F

2016-01-01

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions. PMID:27206265

White Matter Integrity Reductions in Intermittent Explosive Disorder.

PubMed

Lee, Royce; Arfanakis, Konstantinos; Evia, Arnold M; Fanning, Jennifer; Keedy, Sarah; Coccaro, Emil F

2016-10-01

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions.

Network specific change in white matter integrity in mesial temporal lobe epilepsy.

PubMed

Imamura, Hisaji; Matsumoto, Riki; Takaya, Shigetoshi; Nakagawa, Tomokazu; Shimotake, Akihiro; Kikuchi, Takayuki; Sawamoto, Nobukatsu; Kunieda, Takeharu; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

2016-02-01

To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation. Copyright © 2015 Elsevier B.V. All rights reserved.

Cognitive impairment in progressive supranuclear palsy-Richardson's syndrome is related to white matter damage.

PubMed

Caso, Francesca; Agosta, Federica; Volonté, Maria Antonietta; Ferraro, Pilar M; Tiraboschi, Pietro; Copetti, Massimiliano; Valsasina, Paola; Falautano, Monica; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2016-10-01

Beside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs. We enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level. PSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from -0.80 to 0.74). PSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Concurrent white matter bundles and grey matter networks using independent component analysis.

PubMed

O'Muircheartaigh, Jonathan; Jbabdi, Saad

2018-04-15

Developments in non-invasive diffusion MRI tractography techniques have permitted the investigation of both the anatomy of white matter pathways connecting grey matter regions and their structural integrity. In parallel, there has been an expansion in automated techniques aimed at parcellating grey matter into distinct regions based on functional imaging. Here we apply independent component analysis to whole-brain tractography data to automatically extract brain networks based on their associated white matter pathways. This method decomposes the tractography data into components that consist of paired grey matter 'nodes' and white matter 'edges', and automatically separates major white matter bundles, including known cortico-cortical and cortico-subcortical tracts. We show how this framework can be used to investigate individual variations in brain networks (in terms of both nodes and edges) as well as their associations with individual differences in behaviour and anatomy. Finally, we investigate correspondences between tractography-based brain components and several canonical resting-state networks derived from functional MRI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sexually dimorphic white matter geometry abnormalities in adolescent onset schizophrenia.

PubMed

Savadjiev, P; Whitford, T J; Hough, M E; Clemm von Hohenberg, C; Bouix, S; Westin, C-F; Shenton, M E; Crow, T J; James, A C; Kubicki, M

2014-05-01

The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

White matter pathways in persistent developmental stuttering: Lessons from tractography.

PubMed

Kronfeld-Duenias, Vered; Civier, Oren; Amir, Ofer; Ezrati-Vinacour, Ruth; Ben-Shachar, Michal

2018-03-01

Fluent speech production relies on the coordinated processing of multiple brain regions. This highlights the role of neural pathways that connect distinct brain regions in producing fluent speech. Here, we aim to investigate the role of the white matter pathways in persistent developmental stuttering (PDS), where speech fluency is disrupted. We use diffusion weighted imaging and tractography to compare the white matter properties between adults who do and do not stutter. We compare the diffusion properties along 18 major cerebral white matter pathways. We complement the analysis with an overview of the methodology and a roadmap of the pathways implicated in PDS according to the existing literature. We report differences in the microstructural properties of the anterior callosum, the right inferior longitudinal fasciculus and the right cingulum in people who stutter compared with fluent controls. Persistent developmental stuttering is consistently associated with differences in bilateral distributed networks. We review evidence showing that PDS involves differences in bilateral dorsal fronto-temporal and fronto-parietal pathways, in callosal pathways, in several motor pathways and in basal ganglia connections. This entails an important role for long range white matter pathways in this disorder. Using a wide-lens analysis, we demonstrate differences in additional, right hemispheric pathways, which go beyond the replicable findings in the literature. This suggests that the affected circuits may extend beyond the known language and motor pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Probabilistic diffusion tractography reveals improvement of structural network in musicians.

PubMed

Li, Jianfu; Luo, Cheng; Peng, Yueheng; Xie, Qiankun; Gong, Jinnan; Dong, Li; Lai, Yongxiu; Li, Hong; Yao, Dezhong

2014-01-01

Musicians experience a large amount of information transfer and integration of complex sensory, motor, and auditory processes when training and playing musical instruments. Therefore, musicians are a useful model in which to investigate neural adaptations in the brain. Here, based on diffusion-weighted imaging, probabilistic tractography was used to determine the architecture of white matter anatomical networks in musicians and non-musicians. Furthermore, the features of the white matter networks were analyzed using graph theory. Small-world properties of the white matter network were observed in both groups. Compared with non-musicians, the musicians exhibited significantly increased connectivity strength in the left and right supplementary motor areas, the left calcarine fissure and surrounding cortex and the right caudate nucleus, as well as a significantly larger weighted clustering coefficient in the right olfactory cortex, the left medial superior frontal gyrus, the right gyrus rectus, the left lingual gyrus, the left supramarginal gyrus, and the right pallidum. Furthermore, there were differences in the node betweenness centrality in several regions. However, no significant differences in topological properties were observed at a global level. We illustrated preliminary findings to extend the network level understanding of white matter plasticity in musicians who have had long-term musical training. These structural, network-based findings may indicate that musicians have enhanced information transmission efficiencies in local white matter networks that are related to musical training.

Tryptophan Metabolism and White Matter Integrity in Schizophrenia

PubMed Central

Chiappelli, Joshua; Postolache, Teodor T; Kochunov, Peter; Rowland, Laura M; Wijtenburg, S Andrea; Shukla, Dinesh K; Tagamets, Malle; Du, Xiaoming; Savransky, Anya; Lowry, Christopher A; Can, Adem; Fuchs, Dietmar; Hong, L Elliot

2016-01-01

Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and 1H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (p<0.001), and kynurenine/tryptophan ratios were correspondingly higher (p=0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r=0.347, p=0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r=−0.391 and −0.350 respectively, p=0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia. PMID:27143602

Alcohol Use and Cerebral White Matter Compromise in Adolescence

PubMed Central

Elofson, Jonathan; Gongvatana, Win; Carey, Kate B.

2013-01-01

Alcohol use is typically initiated during adolescence, a period known to be critical in neurodevelopment. The adolescent brain may be particularly susceptible to the harmful effects of alcohol. While the cognitive deficits associated with alcohol use during adolescence have been well-documented, the neural substrates underlying these effects remain inadequately understood. Cerebral white matter has been suggested as a primary site of alcohol-related damage and diffusion tensor imaging (DTI) allows for the quantification of white matter integrity in vivo. This review summarizes results from both cross-sectional and longitudinal studies employing DTI that indicate that white matter tracts, particularly those thought to be involved in executive functioning, continue to develop throughout adolescence and into adulthood. Numerous DTI studies reveal a positive correlation between white matter integrity and neurocognitive performance and, in adults, the detrimental effects of prolonged alcohol-dependence on white matter integrity. We provide a comprehensive review of the DTI studies exploring the relationship between alcohol use and white matter integrity in adolescents. Results from most of these studies suggest that alcohol use is associated with reduced white matter integrity, particularly in the superior longitudinal fasciculus (SLF), and some evidence suggests that this relationship may be influenced by sex. We conclude by highlighting confounds and limitations of the available research and suggesting directions for future research. PMID:23583835

Definition and quantification of acute inflammatory white matter injury in the immature brain by MRI/MRS at high magnetic field.

PubMed

Lodygensky, Gregory A; Kunz, Nicolas; Perroud, Elodie; Somm, Emmanuel; Mlynarik, Vladimir; Hüppi, Petra S; Gruetter, Rolf; Sizonenko, Stéphane V

2014-03-01

Lipopolysaccharide (LPS) injection in the corpus callosum (CC) of rat pups results in diffuse white matter injury similar to the main neuropathology of preterm infants. The aim of this study was to characterize the structural and metabolic markers of acute inflammatory injury by high-field magnetic resonance imaging (MRI) magnetic resonance spectroscopy (MRS) in vivo. Twenty-four hours after a 1-mg/kg injection of LPS in postnatal day 3 rat pups, diffusion tensor imaging and proton nuclear magnetic spectroscopy ((1)H NMR) were analyzed in conjunction to determine markers of cell death and inflammation using immunohistochemistry and gene expression. MRI and MRS in the CC revealed an increase in lactate and free lipids and a decrease of the apparent diffusion coefficient. Detailed evaluation of the CC showed a marked apoptotic response assessed by fractin expression. Interestingly, the degree of reduction in the apparent diffusion coefficient correlated strongly with the natural logarithm of fractin expression, in the same region of interest. LPS injection further resulted in increased activated microglia clustered in the cingulum, widespread astrogliosis, and increased expression of genes for interleukin (IL)-1, IL-6, and tumor necrosis factor. This model was able to reproduce the typical MRI hallmarks of acute diffuse white matter injury seen in preterm infants and allowed the evaluation of in vivo biomarkers of acute neuropathology after inflammatory challenge.

Acute white matter changes following sport-related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study.

PubMed

Lancaster, Melissa A; Olson, Daniel V; McCrea, Michael A; Nelson, Lindsay D; LaRoche, Ashley A; Muftuler, L Tugan

2016-11-01

Recent neuroimaging studies have suggested that following sport-related concussion (SRC) physiological brain alterations may persist after an athlete has shown full symptom recovery. Diffusion MRI is a versatile technique to study white matter injury following SRC, yet serial follow-up studies in the very acute stages following SRC utilizing a comprehensive set of diffusion metrics are lacking. The aim of the current study was to characterize white matter changes within 24 hours of concussion in a group of high school and collegiate athletes, using Diffusion Tensor and Diffusion Kurtosis Tensor metrics. Participants were reassessed a week later. At 24 hours post-injury, the concussed group reported significantly more concussion symptoms than a well-matched control group and demonstrated poorer performance on a cognitive screening measure, yet these differences were nonsignificant at the 8-day follow-up. Similarly, within 24-hours after injury, the concussed group exhibited a widespread decrease in mean diffusivity, increased axial kurtosis and, to a lesser extent, decreased axial and radial diffusivities compared with control subjects. At 8 days post injury, the differences in these diffusion metrics were even more widespread in the injured athletes, despite improvement of symptoms and cognitive performance. These MRI findings suggest that the athletes might not have reached full physiological recovery a week after the injury. These findings have significant implications for the management of SRC because allowing an athlete to return to play before the brain has fully recovered from injury may have negative consequences. Hum Brain Mapp 37:3821-3834, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia.

PubMed

Alba-Ferrara, L M; de Erausquin, Gabriel A

2013-01-01

Schizophrenia is a common, severe, and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI). Indices commonly derived from DTI include (1) mean diffusivity, independent of direction, (2) fractional anisotropy (FA) or relative anisotropy (RA), (3) axial diffusivity, and (4) radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes (OLG), and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased FA in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis

PubMed Central

Lin, Tsen-Hsuan; Spees, William M.; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further elucidate the interplay of underlying pathologies and functional impairments. Previously, we demonstrated a significant 27% activation-associated decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) in normal C57BL/6 mouse optic nerve with visual stimulation using diffusion fMRI. Here we apply this approach to explore the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis. Visual stimulation produced a significant 25% (vs. baseline) ADC⊥ decrease in sham EAE optic nerves, while only a 7% (vs. baseline) ADC⊥ decrease was seen in EAE mice with acute optic neuritis. The reduced activation-associated ADC⊥ response correlated with post-MRI immunohistochemistry determined pathologies (including inflammation, demyelination, and axonal injury). The negative correlation between activation-associated ADC⊥ response and visual acuity was also found when pooling EAE-affected and sham groups under our experimental criteria. Results suggest that reduction in diffusion fMRI directly reflects impaired axonal-activation in EAE mice with optic neuritis. Diffusion fMRI holds promise for directly gauging in vivo white-matter dysfunction or therapeutic responses in MS patients. PMID:24632420

Three-dimensional high-resolution diffusion tensor imaging and tractography of the developing rabbit brain.

PubMed

D'Arceuil, Helen; Liu, Christina; Levitt, Pat; Thompson, Barbara; Kosofsky, Barry; de Crespigny, Alex

2008-01-01

Diffusion tensor imaging (DTI) is sensitive to structural ordering in brain tissue particularly in the white matter tracts. Diffusion anisotropy changes with disease and also with neural development. We used high-resolution DTI of fixed rabbit brains to study developmental changes in regional diffusion anisotropy and white matter fiber tract development. Imaging was performed on a 4.7-tesla Bruker Biospec Avance scanner using custom-built solenoid coils and DTI was performed at various postnatal ages. Trace apparent diffusion coefficient, fractional diffusion anisotropy maps and fiber tracts were generated and compared across the ages. The brain was highly anisotropic at birth and white matter anisotropy increased with age. Regional DTI tractography of the internal capsule showed refinement in regional tract architecture with maturation. Interestingly, brains with congenital deficiencies of the callosal commissure showed selectively strikingly different fiber architecture compared to age-matched brains. There was also some evidence of subcortical to cortical fiber connectivity. DTI tractography of the anterior and posterior limbs of the internal capsule showed reproducibly coherent fiber tracts corresponding to known corticospinal and corticobulbar tract anatomy. There was some minor interanimal tract variability, but there was remarkable similarity between the tracts in all animals. Therefore, ex vivo DTI tractography is a potentially powerful tool for neuroscience investigations and may also reveal effects (such as fiber tract pruning during development) which may be important targets for in vivo human studies. Copyright 2007 S. Karger AG, Basel.

ApoE influences regional white-matter axonal density loss in Alzheimer's disease.

PubMed

Slattery, Catherine F; Zhang, Jiaying; Paterson, Ross W; Foulkes, Alexander J M; Carton, Amelia; Macpherson, Kirsty; Mancini, Laura; Thomas, David L; Modat, Marc; Toussaint, Nicolas; Cash, David M; Thornton, John S; Henley, Susie M D; Crutch, Sebastian J; Alexander, Daniel C; Ourselin, Sebastien; Fox, Nick C; Zhang, Hui; Schott, Jonathan M

2017-09-01

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

PubMed

Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

2017-06-01

The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

PubMed Central

Lockhart, Samuel N.; Mayda, Adriane B. V.; Roach, Alexandra E.; Fletcher, Evan; Carmichael, Owen; Maillard, Pauline; Schwarz, Christopher G.; Yonelinas, Andrew P.; Ranganath, Charan; DeCarli, Charles

2011-01-01

Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH) and fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI), differ with aging and cerebrovascular disease (CVD) and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals. PMID:22438841

Effect of cerebral spinal fluid suppression for diffusional kurtosis imaging.

PubMed

Yang, Alicia W; Jensen, Jens H; Hu, Caixia C; Tabesh, Ali; Falangola, Maria F; Helpern, Joseph A

2013-02-01

To evaluate the cerebral spinal fluid (CSF) partial volume effect on diffusional kurtosis imaging (DKI) metrics in white matter and cortical gray matter. Four healthy volunteers participated in this study. Standard DKI and fluid-attenuated inversion recovery (FLAIR) DKI experiments were performed using a twice-refocused-spin-echo diffusion sequence. The conventional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, D[symbol in text], D[symbol in text] together with DKI metrics of mean, axial, and radial kurtosis (MK, K[symbol in text], K[symbol in text], were measured and compared. Single image slices located above the lateral ventricles, with similar anatomical features for each subject, were selected to minimize the effect of CSF from the ventricles. In white matter, differences of less than 10% were observed between diffusion metrics measured with standard DKI and FLAIR-DKI sequences, suggesting minimal CSF contamination. For gray matter, conventional DTI metrics differed by 19% to 52%, reflecting significant CSF partial volume effects. Kurtosis metrics, however, changed by 11% or less, indicating greater robustness with respect to CSF contamination. Kurtosis metrics are less sensitive to CSF partial voluming in cortical gray matter than conventional diffusion metrics. The kurtosis metrics may then be more specific indicators of changes in tissue microstructure, provided the effect sizes for the changes are comparable. Copyright © 2012 Wiley Periodicals, Inc.

Central Nervous System Brucellosis Granuloma and White Matter Disease in Immunocompromised Patient

PubMed Central

Al-Ajlan, Fahad S.; Al-Hindi, Hindi; Al Semari, Abdulaziz

2017-01-01

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen. PMID:28518039

Delay of gratification is associated with white matter connectivity in the dorsal prefrontal cortex: a diffusion tensor imaging study in chimpanzees (Pan troglodytes).

PubMed

Latzman, Robert D; Taglialatela, Jared P; Hopkins, William D

2015-06-22

Individual variability in delay of gratification (DG) is associated with a number of important outcomes in both non-human and human primates. Using diffusion tensor imaging (DTI), this study describes the relationship between probabilistic estimates of white matter tracts projecting from the caudate to the prefrontal cortex (PFC) and DG abilities in a sample of 49 captive chimpanzees (Pan troglodytes). After accounting for time between collection of DTI scans and DG measurement, age and sex, higher white matter connectivity between the caudate and right dorsal PFC was found to be significantly associated with the acquisition (i.e. training phase) but not the maintenance of DG abilities. No other associations were found to be significant. The integrity of white matter connectivity between regions of the striatum and the PFC appear to be associated with inhibitory control in chimpanzees, with perturbations on this circuit potentially leading to a variety of maladaptive outcomes. Additionally, results have potential translational implications for understanding the pathophysiology of a number of psychiatric and clinical outcomes in humans. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study

PubMed Central

Mahon, Katie; Burdick, Katherine E; Wu, Jinghui; Ardekani, Babak A; Szeszko, Philip R

2012-01-01

Background Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well-investigated. Methods Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract-Based Spatial Statistics method in the FSL software package. Results Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity. Conclusions Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder. PMID:22329475

Radial Coherence of Diffusion Tractography in the Cerebral White Matter of the Human Fetus: Neuroanatomic Insights

PubMed Central

Xu, Gang; Takahashi, Emi; Folkerth, Rebecca D.; Haynes, Robin L.; Volpe, Joseph J.; Grant, P. Ellen; Kinney, Hannah C.

2014-01-01

High angular resolution diffusion imaging (HARDI) demonstrates transient radial coherence of telencephalic white matter in the human fetus. Our objective was to define the neuroanatomic basis of this radial coherence through correlative HARDI- and postmortem tissue analyses. Applying immunomarkers to radial glial fibers (RGFs), axons, and blood vessels in 18 cases (19 gestational weeks to 3 postnatal years), we compared their developmental profiles to HARDI tractography in brains of comparable ages (n = 11). At midgestation, radial coherence corresponded with the presence of RGFs. At 30–31 weeks, the transition from HARDI-defined radial coherence to corticocortical coherence began simultaneously with the transformation of RGFs to astrocytes. By term, both radial coherence and RGFs had disappeared. White matter axons were radial, tangential, and oblique over the second half of gestation, whereas penetrating blood vessels were consistently radial. Thus, radial coherence in the fetal white matter likely reflects a composite of RGFs, penetrating blood vessels, and radial axons of which its transient expression most closely matches that of RGFs. This study provides baseline information for interpreting radial coherence in tractography studies of the preterm brain in the assessment of the encephalopathy of prematurity. PMID:23131806

Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

PubMed Central

Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

2011-01-01

The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

A challenging issue: Detection of white matter hyperintensities in neonatal brain MRI.

PubMed

Morel, Baptiste; Yongchao Xu; Virzi, Alessio; Geraud, Thierry; Adamsbaum, Catherine; Bloch, Isabelle

2016-08-01

The progress of magnetic resonance imaging (MRI) allows for a precise exploration of the brain of premature infants at term equivalent age. The so-called DEHSI (diffuse excessive high signal intensity) of the white matter of premature brains remains a challenging issue in terms of definition, and thus of interpretation. We propose a semi-automatic detection and quantification method of white matter hyperintensities in MRI relying on morphological operators and max-tree representations, which constitutes a powerful tool to help radiologists to improve their interpretation. Results show better reproducibility and robustness than interactive segmentation.

Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism-like behavior in a rat model of diffuse white matter injury.

PubMed

van Tilborg, Erik; Achterberg, E J Marijke; van Kammen, Caren M; van der Toorn, Annette; Groenendaal, Floris; Dijkhuizen, Rick M; Heijnen, Cobi J; Vanderschuren, Louk J M J; Benders, Manon N J L; Nijboer, Cora H A

2018-01-01

Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism-spectrum disorders. Important risk factors include fetal or perinatal inflammatory insults and fluctuating cerebral oxygenation. However, the exact mechanisms underlying diffuse WMI are not fully understood and no treatment options are currently available. The use of clinically relevant animal models is crucial to advance knowledge on the pathophysiology of diffuse WMI, allowing the definition of novel therapeutic targets. In the present study, we developed a multiple-hit animal model of diffuse WMI by combining fetal inflammation and postnatal hypoxia in rats. We characterized the effects on white matter development and functional outcome by immunohistochemistry, MRI and behavioral paradigms. Combined fetal inflammation and postnatal hypoxia resulted in delayed cortical myelination, microglia activation and astrogliosis at P18, together with long-term changes in oligodendrocyte maturation as observed in 10 week old animals. Furthermore, rats with WMI showed impaired motor performance, increased anxiety and signs of autism-like behavior, i.e. reduced social play behavior and increased repetitive grooming. In conclusion, the combination of fetal inflammation and postnatal hypoxia in rats induces a pattern of brain injury and functional impairments that closely resembles the clinical situation of diffuse WMI. This animal model provides the opportunity to elucidate pathophysiological mechanisms underlying WMI, and can be used to develop novel treatment options for diffuse WMI in preterm infants. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism‐like behavior in a rat model of diffuse white matter injury

PubMed Central

van Tilborg, Erik; Achterberg, E. J. Marijke; van Kammen, Caren M.; van der Toorn, Annette; Groenendaal, Floris; Dijkhuizen, Rick M.; Heijnen, Cobi J.; Vanderschuren, Louk J. M. J.; Benders, Manon N. J. L.

2017-01-01

Abstract Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism‐spectrum disorders. Important risk factors include fetal or perinatal inflammatory insults and fluctuating cerebral oxygenation. However, the exact mechanisms underlying diffuse WMI are not fully understood and no treatment options are currently available. The use of clinically relevant animal models is crucial to advance knowledge on the pathophysiology of diffuse WMI, allowing the definition of novel therapeutic targets. In the present study, we developed a multiple‐hit animal model of diffuse WMI by combining fetal inflammation and postnatal hypoxia in rats. We characterized the effects on white matter development and functional outcome by immunohistochemistry, MRI and behavioral paradigms. Combined fetal inflammation and postnatal hypoxia resulted in delayed cortical myelination, microglia activation and astrogliosis at P18, together with long‐term changes in oligodendrocyte maturation as observed in 10 week old animals. Furthermore, rats with WMI showed impaired motor performance, increased anxiety and signs of autism‐like behavior, i.e. reduced social play behavior and increased repetitive grooming. In conclusion, the combination of fetal inflammation and postnatal hypoxia in rats induces a pattern of brain injury and functional impairments that closely resembles the clinical situation of diffuse WMI. This animal model provides the opportunity to elucidate pathophysiological mechanisms underlying WMI, and can be used to develop novel treatment options for diffuse WMI in preterm infants. PMID:28925578

Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age.

PubMed

Hatton, Sean N; Panizzon, Matthew S; Vuoksimaa, Eero; Hagler, Donald J; Fennema-Notestine, Christine; Rinker, Daniel; Eyler, Lisa T; Franz, Carol E; Lyons, Michael J; Neale, Michael C; Tsuang, Ming T; Dale, Anders M; Kremen, William S

2018-05-01

Two basic neuroimaging-based characterizations of white matter tracts are the magnitude of water diffusion along the principal tract orientation (axial diffusivity, AD) and water diffusion perpendicular to the principal orientation (radial diffusivity, RD). It is generally accepted that decreases in AD reflect disorganization, damage, or loss of axons, whereas increases in RD are indicative of disruptions to the myelin sheath. Previous reports have detailed the heritability of individual AD and RD measures, but have not examined the extent to which the same or different genetic or environmental factors influence these two phenotypes (except for corpus callosum). We implemented bivariate twin analyses to examine the shared and independent genetic influences on AD and RD. In the Vietnam Era Twin Study of Aging, 393 men (mean age = 61.8 years, SD = 2.6) underwent diffusion-weighted magnetic resonance imaging. We derived fractional anisotropy (FA), mean diffusivity (MD), AD, and RD estimates for 11 major bilateral white matter tracts and the mid-hemispheric corpus callosum, forceps major, and forceps minor. Separately, AD and RD were each highly heritable. In about three-quarters of the tracts, genetic correlations between AD and RD were >.50 (median = .67) and showed both unique and common variance. Genetic variance of FA and MD were predominately explained by RD over AD. These findings are important for informing genetic association studies of axonal coherence/damage and myelination/demyelination. Thus, genetic studies would benefit from examining the shared and unique contributions of AD and RD. © 2018 Wiley Periodicals, Inc.

Diffusion MRI at 25: Exploring brain tissue structure and function

PubMed Central

Bihan, Denis Le; Johansen-Berg, Heidi

2013-01-01

Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state. PMID:22120012

Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: in vivo assessment of structural changes.

PubMed

Castellano, Antonella; Papinutto, Nico; Cadioli, Marcello; Brugnara, Gianluca; Iadanza, Antonella; Scigliuolo, Graziana; Pareyson, Davide; Uziel, Graziella; Köhler, Wolfgang; Aubourg, Patrick; Falini, Andrea; Henry, Roland G; Politi, Letterio S; Salsano, Ettore

2016-06-01

Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases. Moreover, little is known about the subtle pathological changes that can characterize the brain of adrenomyeloneuropathy subjects in the early stages of the disease. We performed a cross-sectional study on 13 patients with adrenomyeloneuropathy and 12 age-matched healthy control subjects who underwent quantitative magnetic resonance imaging to assess the structural changes of the upper spinal cord and brain. Total cord areas from C2-3 to T2-3 level were measured, and diffusion tensor imaging metrics, i.e. fractional anisotropy, mean, axial and radial diffusivity values were calculated in both grey and white matter of spinal cord. In the brain, grey matter regions were parcellated with Freesurfer and average volume and thickness, and mean diffusivity and fractional anisotropy from co-registered diffusion maps were calculated in each region. Brain white matter diffusion tensor imaging metrics were assessed using whole-brain tract-based spatial statistics, and tractography-based analysis on corticospinal tracts. Correlations among clinical, structural and diffusion tensor imaging measures were calculated. In patients total cord area was reduced by 26.3% to 40.2% at all tested levels (P < 0.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P ≤ 0.0003) with a concomitant 9.7% axial diffusivity reduction (P < 0.009) and 34.5% radial diffusivity increase (P < 0.009) was observed, suggesting co-presence of axonal degeneration and demyelination. Brain tract-based spatial statistics showed a marked reduction of fractional anisotropy, increase of radial diffusivity (P < 0.001) and no axial diffusivity changes in several white matter tracts, including corticospinal tracts and optic radiations, indicating predominant demyelination. Tractography-based analysis confirmed the results within corticospinal tracts. No significant cortical volume and thickness reduction or grey matter diffusion tensor imaging values alterations were observed in patients. A correlation between radial diffusivity and disease duration along the corticospinal tracts (r = 0.806, P < 0.01) was found. In conclusion, in adrenomyeloneuropathy patients quantitative magnetic resonance imaging-derived measures identify and quantify structural changes in the upper spinal cord and brain which agree with the expected histopathology, and suggest that the disease could be primarily caused by a demyelination rather than a primitive axonal damage. The results of this study may also encourage the employment of quantitative magnetic resonance imaging in other hereditary diseases with spinal cord involvement. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron

PubMed Central

Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

2014-01-01

In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients. PMID:24899728

Epigenetic Age Acceleration Assessed with Human White-Matter Images.

PubMed

Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

2017-05-03

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age, relative to chronological age. The white matter tracts within the brain are also highly sensitive to aging processes. We show that increased biological aging (measured using epigenetic data from blood samples) is correlated with reduced integrity of white matter tracts within the human brain (measured using diffusion tensor imaging) with data from a large sample of Mexican-American families. Given the family design of the sample, we are also able to demonstrate that epigenetic aging and white matter tract integrity also share common genetic influences. Therefore, epigenetic age may be a potential, and accessible, biomarker of brain aging. Copyright © 2017 the authors 0270-6474/17/374735-09$15.00/0.

Age-related white matter integrity differences in oldest-old without dementia.

PubMed

Bennett, Ilana J; Greenia, Dana E; Maillard, Pauline; Sajjadi, S Ahmad; DeCarli, Charles; Corrada, Maria M; Kawas, Claudia H

2017-08-01

Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life. Copyright © 2017 Elsevier Inc. All rights reserved.

Coupled changes in brain white matter microstructure and fluid intelligence in later life.

PubMed

Ritchie, Stuart J; Bastin, Mark E; Tucker-Drob, Elliot M; Maniega, Susana Muñoz; Engelhardt, Laura E; Cox, Simon R; Royle, Natalie A; Gow, Alan J; Corley, Janie; Pattie, Alison; Taylor, Adele M; Valdés Hernández, Maria Del C; Starr, John M; Wardlaw, Joanna M; Deary, Ian J

2015-06-03

Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical "disconnection" partly explains cognitive aging. Copyright © 2015 Ritchie et al.

Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism.

PubMed

Pfefferbaum, Adolf; Adalsteinsson, Elfar; Sullivan, Edith V

2006-07-01

Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.

Longitudinal Processing Speed Impairments in Males with Autism and the Effects of White Matter Microstructure

PubMed Central

Travers, Brittany G.; Bigler, Erin D.; Tromp, Do P. M.; Adluru, Nagesh; Froehlich, Alyson L.; Ennis, Chad; Lange, Nicholas; Nielsen, Jared A.; Prigge, Molly B. D.; Alexander, Andrew L.; Lainhart, Janet E.

2014-01-01

The present study used an accelerated longitudinal design to examine group differences and age-related changes in processing speed in 81 individuals with Autism Spectrum Disorder (ASD) compared to 56 age-matched individuals with typical development (ages 6–39 years). Processing speed was assessed using the Wechsler Intelligence Scale for Children-3rd edition (WISC-III) and the Wechsler Adult Intelligence Scale-3rd edition (WAIS-III). Follow-up analyses examined processing speed subtest performance and relations between processing speed and white matter microstructure (as measured with diffusion tensor imaging [DTI] in a subset of these participants). After controlling for full scale IQ, the present results show that processing speed index standard scores were on average 12 points lower in the group with ASD compared to the group with typical development. There were, however, no significant group differences in standard score age-related changes within this age range. For subtest raw scores, the group with ASD demonstrated robustly slower processing speeds in the adult versions of the IQ test (i.e., WAIS-III) but not in the child versions (WISC-III), even though age-related changes were similar in both the ASD and typically developing groups. This pattern of results may reflect difficulties that become increasingly evident in ASD on more complex measures of processing speed. Finally, DTI measures of whole-brain white matter microstructure suggested that fractional anisotropy (but not mean diffusivity, radial diffusivity, or axial diffusivity) made significant but small-sized contributions to processing speed standard scores across our entire sample. Taken together, the present findings suggest that robust decreases in processing speed may be present in ASD, more pronounced in adulthood, and partially attributable to white matter microstructural integrity. PMID:24269298

Diffusion Tensor Imaging in Relation to Cognitive and Functional Outcome of Traumatic Brain Injury in Children

PubMed Central

Levin, Harvey S.; Wilde, Elisabeth A.; Chu, Zili; Yallampalli, Ragini; Hanten, Gerri R.; Li, Xiaoqi; Chia, Jon; Vasquez, Carmen; Hunter, Jill V.

2008-01-01

Objective To investigate the relation of white matter integrity using diffusion tensor imaging (DTI) to cognitive and functional outcome of moderate to severe traumatic brain injury (TBI) in children. Design Prospective observational study of children who had sustained moderate to severe TBI and a comparison group of children who had sustained orthopedic injury (OI). Participants Thirty-two children who had sustained moderate to severe TBI and 36 children with OI were studied. Methods Fiber tracking analysis of DTI acquired at 3-month postinjury and assessment of global outcome and cognitive function within 2 weeks of brain imaging. Global outcome was assessed using the Glasgow Outcome Scale and the Flanker task was used to measure cognitive processing speed and resistance to interference. Results Fractional anisotropy and apparent diffusion coefficient values differentiated the groups and both cognitive and functional outcome measures were related to the DTI findings. Dissociations were present wherein the relation of Fractional anisotropy to cognitive performance differed between the TBI and OI groups. A DTI composite measure of white matter integrity was related to global outcome in the children with TBI. Conclusions DTI is sensitive to white matter injury at 3 months following moderate to severe TBI in children, including brain regions that appear normal on conventional magnetic resonance imaging. DTI measures reflecting diffusion of water parallel and perpendicular to white matter tracts as calculated by fiber tracking analysis are related to global outcome, cognitive processing speed, and speed of resolving interference in children with moderate to severe TBI. Longitudinal data are needed to determine whether these relations between DTI and neurobehavioral outcome of TBI in children persist at longer follow-up intervals. PMID:18650764

The impact of human immune deficiency virus and hepatitis C coinfection on white matter microstructural integrity.

PubMed

Heaps-Woodruff, J M; Wright, P W; Ances, B M; Clifford, D; Paul, R H

2016-06-01

The purpose of the present study is to examine the integrity of white matter microstructure among individuals coinfected with HIV and HCV using diffusion tensor imaging (DTI). Twenty-five HIV+ patients, 21 HIV+/HCV+ patients, and 25 HIV- controls were included in this study. All HIV+ individuals were stable on combination antiretroviral therapy (cART; ≥3 months). All participants completed MRI and neuropsychological measures. Clinical variables including liver function, HIV-viral load, and CD4 count were collected from the patient groups. DTI metrics including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) from five subregions of the corpus callosum were compared across groups. The HIV+/HCV+ group and HIV+ group were similar in terms of HIV clinical variables. None of the participants met criteria for cirrhosis or fibrosis. Within the anterior corpus callosum, significant differences were observed between both HIV+ groups compared to HIV- controls on DTI measures. HIV+ and HIV+/HCV+ groups had significantly lower FA values and higher MD and RD values compared to HIV- controls; however, no differences were present between the HIV+ and HIV+/HCV+ groups. Duration of HIV infection was significantly related to DTI metrics in total corpus callosum FA only, but not other markers of HIV disease burden or neurocognitive function. Both HIV+ and HIV+/HCV+ individuals had significant alterations in white matter integrity within the corpus callosum; however, there was no evidence for an additive effect of HCV coinfection. The association between DTI metrics and duration of HIV infection suggests that HIV may continue to negatively impact white matter integrity even in well-controlled disease.

White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults.

PubMed

Oberlin, Lauren E; Verstynen, Timothy D; Burzynska, Agnieszka Z; Voss, Michelle W; Prakash, Ruchika Shaurya; Chaddock-Heyman, Laura; Wong, Chelsea; Fanning, Jason; Awick, Elizabeth; Gothe, Neha; Phillips, Siobhan M; Mailey, Emily; Ehlers, Diane; Olson, Erin; Wojcicki, Thomas; McAuley, Edward; Kramer, Arthur F; Erickson, Kirk I

2016-05-01

White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety

PubMed Central

Clewett, David; Bachman, Shelby; Mather, Mara

2014-01-01

Objective A current neuroanatomical model of anxiety posits that greater structural connectivity between the amygdala and ventral prefrontal cortex (vPFC) facilitates regulatory control over the amygdala and helps reduce anxiety. However, some neuroimaging studies have reported contradictory findings, demonstrating a positive rather than negative association between trait anxiety and amygdala-vPFC white matter integrity. To help reconcile these findings, we tested the regulatory hypothesis of anxiety circuitry using aging as a model of white matter decline in the amygdala-vPFC pathway. Methods We used probabilistic tractography to trace connections between the amygdala and vPFC in 21 younger, 18 middle-aged, and 15 healthy older adults. The resulting tract estimates were used to extract three indices of white-matter integrity: fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD). The relationship between these amygdala-vPFC structural connectivity measures and age and State-Trait Anxiety Inventory (STAI) scores were assessed. Results The tractography results revealed age-related decline in the FA (p = .005) and radial diffusivity (p = .002) of the amygdala-vPFC pathway. Contrary to the regulatory hypothesis, we found a positive rather than negative association between trait anxiety and right amygdala-vPFC FA (p = .01). Conclusion These findings argue against the notion that greater amygdala-vPFC structural integrity facilitates better anxiety outcomes in healthy adults. Instead, our results suggest that white matter degeneration in this network relates to lower anxiety in older adults. PMID:24635708

MRI and (1)H-MRS in adenosine kinase deficiency.

PubMed

Staufner, C; Blom, H J; Dionisi-Vici, C; Freisinger, P; Makhseed, N; Ballhausen, D; Kölker, S; Hoffmann, G F; Harting, I

2016-07-01

Adenosine kinase deficiency (ADK deficiency) is a recently described disorder of methionine and adenosine metabolism resulting in a neurological phenotype with developmental delay, muscular hypotonia, and epilepsy as well as variable systemic manifestations. The underlying neuropathology is poorly understood. We have investigated MRI and (1)H-MRS changes in ADK deficiency in order to better understand the in vivo neuropathologic changes of ADK deficiency. Systematic evaluation of 21 MRIs from eight patients (age range 9 days-14.6 years, mean 3.9 years, median 2.7 years) including diffusion-weighted imaging in six and (1)H-MRS in five patients. Brain maturation was delayed in the neonatal period and in infancy (6/6), but ultimately complete. White matter changes occurring in five of eight patients were discrete, periventricular, and unspecific (4/5), or diffuse with sparing of optic radiation, corona radiata, and pyramidal tracts (1/5). Choline was low in white matter spectra (3/3), while there was no indication of low creatine in white matter or basal ganglia (5/5), and diffusion was variably decreased or increased. Central tegmental tract hyperintensity was a common finding (6/8), as was supratentorial atrophy (6/8). MRI changes in ADK deficiency consist of delayed but ultimately completed brain maturation with later onset of mostly unspecific white matter changes and potentially transient central tegmental tract hyperintensity. Immaturity on neonatal MRI is consistent with prenatal onset of disease and reduced choline with lower membrane turnover resulting in delayed myelination and deficient myelin maintenance.

Toward Precision and Reproducibility of Diffusion Tensor Imaging: A Multicenter Diffusion Phantom and Traveling Volunteer Study.

PubMed

Palacios, E M; Martin, A J; Boss, M A; Ezekiel, F; Chang, Y S; Yuh, E L; Vassar, M J; Schnyer, D M; MacDonald, C L; Crawford, K L; Irimia, A; Toga, A W; Mukherjee, P

2017-03-01

Precision medicine is an approach to disease diagnosis, treatment, and prevention that relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of this study was to assess the intersite variability after harmonization of a high-angular-resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury multisite study. Diffusion MR imaging was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology and from the brain of a traveling volunteer on thirteen 3T MR imaging scanners representing 3 major vendors (GE Healthcare, Philips Healthcare, and Siemens). Means of the DTI parameters and their coefficients of variation across scanners were calculated for each DTI metric and white matter tract. For the National Institute of Standards and Technology diffusion phantom, the coefficients of variation of the apparent diffusion coefficient across the 13 scanners was <3.8% for a range of diffusivities from 0.4 to 1.1 × 10 -6 mm 2 /s. For the volunteer, the coefficients of variations across scanners of the 4 primary DTI metrics, each averaged over the entire white matter skeleton, were all <5%. In individual white matter tracts, large central pathways showed good reproducibility with the coefficients of variation consistently below 5%. However, smaller tracts showed more variability, with the coefficients of variation of some DTI metrics reaching 10%. The results suggest the feasibility of standardizing DTI across 3T scanners from different MR imaging vendors in a large-scale neuroimaging research study. © 2017 by American Journal of Neuroradiology.

White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

PubMed

Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

2014-07-01

The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

Cortico-Cortical White Matter Motor Pathway Microstructure Is Related to Psychomotor Retardation in Major Depressive Disorder

PubMed Central

Bracht, Tobias; Federspiel, Andrea; Schnell, Susanne; Horn, Helge; Höfle, Oliver; Wiest, Roland; Dierks, Thomas; Strik, Werner; Müller, Thomas J.; Walther, Sebastian

2012-01-01

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD. PMID:23284950

Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder.

PubMed

Bracht, Tobias; Federspiel, Andrea; Schnell, Susanne; Horn, Helge; Höfle, Oliver; Wiest, Roland; Dierks, Thomas; Strik, Werner; Müller, Thomas J; Walther, Sebastian

2012-01-01

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.

PubMed

Duncan, Jhodie Rubina; Dick, Alec Lindsay Ward; Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

2012-01-01

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T₂-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence.

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

PubMed Central

Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

2012-01-01

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T2-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence. PMID:23028622

High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

DTIC Science & Technology

2011-12-01

interpreted in standard neuropsychological assessment. Given the relevance of this finding to the hypothesis, we further examined the mechanisms ... mechanism behind this finding. Figure 6.Tractography used to differentiate short and long-range white matter fiber tracts. Figure 7...further investigated as a mechanism underlying impairment. This is shown in Figure 9. 15 Figure 9. Relationship between thalamic FA and cognition

Spatial coherence of oriented white matter microstructure: Applications to white matter regions associated with genetic similarity.

PubMed

Hallgrímsson, Haraldur T; Cieslak, Matthew; Foschini, Luca; Grafton, Scott T; Singh, Ambuj K

2018-05-15

We present a method to discover differences between populations with respect to the spatial coherence of their oriented white matter microstructure in arbitrarily shaped white matter regions. This method is applied to diffusion MRI scans of a subset of the Human Connectome Project dataset: 57 pairs of monozygotic and 52 pairs of dizygotic twins. After controlling for morphological similarity between twins, we identify 3.7% of all white matter as being associated with genetic similarity (35.1 k voxels, p<10 -4 , false discovery rate 1.5%), 75% of which spatially clusters into twenty-two contiguous white matter regions. Furthermore, we show that the orientation similarity within these regions generalizes to a subset of 47 pairs of non-twin siblings, and show that these siblings are on average as similar as dizygotic twins. The regions are located in deep white matter including the superior longitudinal fasciculus, the optic radiations, the middle cerebellar peduncle, the corticospinal tract, and within the anterior temporal lobe, as well as the cerebellum, brain stem, and amygdalae. These results extend previous work using undirected fractional anisotrophy for measuring putative heritable influences in white matter. Our multidirectional extension better accounts for crossing fiber connections within voxels. This bottom up approach has at its basis a novel measurement of coherence within neighboring voxel dyads between subjects, and avoids some of the fundamental ambiguities encountered with tractographic approaches to white matter analysis that estimate global connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Pathways to Seeing Music: Enhanced Structural Connectivity in Colored-Music Synesthesia

PubMed Central

Zamm, Anna; Schlaug, Gottfried; Eagleman, David M.; Loui, Psyche

2013-01-01

Synesthesia, a condition in which a stimulus in one sensory modality consistently and automatically triggers concurrent percepts in another modality, provides a window into the neural correlates of cross-modal associations. While research on grapheme-color synesthesia has provided evidence for both hyperconnectivity/hyperbinding and disinhibited feedback as possible underlying mechanisms, less research has explored the neuroanatomical basis of other forms of synesthesia. In the current study we investigated the white matter correlates of colored-music synesthesia. As these synesthetes report seeing colors upon hearing musical sounds, we hypothesized they might show different patterns of connectivity between visual and auditory association areas. We used diffusion tensor imaging to trace the white matter tracts in temporal and occipital lobe regions in 10 synesthetes and 10 matched non-synesthete controls. Results showed that synesthetes possessed different hemispheric patterns of fractional anisotropy, an index of white matter integrity, in the inferior fronto-occipital fasciculus (IFOF), a major white matter pathway that connects visual and auditory association areas to frontal regions. Specifically, white matter integrity within the right IFOF was significantly greater in synesthetes than controls. Furthermore, white matter integrity in synesthetes was correlated with scores on audiovisual tests of the Synesthesia Battery, especially in white matter underlying the right fusiform gyrus. Our findings provide the first evidence of a white matter substrate of colored-music synesthesia, and suggest that enhanced white matter connectivity is involved in enhanced cross-modal associations. PMID:23454047

A probabilistic atlas of the cerebellar white matter.

PubMed

van Baarsen, K M; Kleinnijenhuis, M; Jbabdi, S; Sotiropoulos, S N; Grotenhuis, J A; van Cappellen van Walsum, A M

2016-01-01

Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study.

PubMed

van der Eerden, Anke W; Khalilzadeh, Omid; Perlbarg, Vincent; Dinkel, Julien; Sanchez, Paola; Vos, Pieter E; Luyt, Charles-Edouard; Stevens, Robert D; Menjot de Champfleur, Nicolas; Delmaire, Christine; Tollard, Eleonore; Gupta, Rajiv; Dormont, Didier; Laureys, Steven; Benali, Habib; Vanhaudenhuyse, Audrey; Galanaud, Damien; Puybasset, Louis

2014-02-01

To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ⊥) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ⊥ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ⊥ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ⊥ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans. © RSNA, 2013

Diffusion Tensor Imaging of the Cerebellum and Eyeblink Conditioning in Fetal Alcohol Spectrum Disorder

PubMed Central

Spottiswoode, B.S.; Meintjes, E.M.; Anderson, A.W.; Molteno, C.D.; Stanton, M.E.; Dodge, N.C.; Gore, J.C.; Peterson, B.S.; Jacobson, J.L.; Jacobson, S.W.

2011-01-01

Background Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique which has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol-related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles. Methods 13 children with fetal alcohol spectrum disorder (FASD) and 12 matched controls were scanned using DTI and structural MRI sequences. The DTI data were processed using a voxelwise technique, and the structural data were used for volumetric analyses. Prenatal alcohol exposure group and EBC performance were examined in relation to brain volumes and outputs from the DTI analysis. Results FA and perpendicular diffusivity group differences between alcohol-exposed and nonexposed children were identified in the left middle cerebellar peduncle. Alcohol exposure correlated with lower fractional anisotropy (FA) and greater perpendicular diffusivity in this region, and these correlations remained significant even after controlling for total brain and cerebellar volume. Conversely, trace conditioning performance was related to higher FA and lower perpendicular diffusivity in the left middle peduncle. The effect of prenatal alcohol exposure on trace conditioning was partially mediated by lower FA in this region. Conclusions This study extends recent findings that have used DTI to reveal microstructural deficits in white matter in children with FASD. This is the first DTI study to demonstrate mediation of a fetal alcohol-related effect on neuropsychological function by deficits in white matter integrity. PMID:21790667

Diffusion-tensor imaging of major white matter tracts and their role in language processing in aphasia.

PubMed

Ivanova, Maria V; Isaev, Dmitry Yu; Dragoy, Olga V; Akinina, Yulia S; Petrushevskiy, Alexey G; Fedina, Oksana N; Shklovsky, Victor M; Dronkers, Nina F

2016-12-01

A growing literature is pointing towards the importance of white matter tracts in understanding the neural mechanisms of language processing, and determining the nature of language deficits and recovery patterns in aphasia. Measurements extracted from diffusion-weighted (DW) images provide comprehensive in vivo measures of local microstructural properties of fiber pathways. In the current study, we compared microstructural properties of major white matter tracts implicated in language processing in each hemisphere (these included arcuate fasciculus (AF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), inferior frontal-occipital fasciculus (IFOF), uncinate fasciculus (UF), and corpus callosum (CC), and corticospinal tract (CST) for control purposes) between individuals with aphasia and healthy controls and investigated the relationship between these neural indices and language deficits. Thirty-seven individuals with aphasia due to left hemisphere stroke and eleven age-matched controls were scanned using DW imaging sequences. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) values for each major white matter tract were extracted from DW images using tract masks chosen from standardized atlases. Individuals with aphasia were also assessed with a standardized language test in Russian targeting comprehension and production at the word and sentence level. Individuals with aphasia had significantly lower FA values for left hemisphere tracts and significantly higher values of MD, RD and AD for both left and right hemisphere tracts compared to controls, all indicating profound impairment in tract integrity. Language comprehension was predominantly related to integrity of the left IFOF and left ILF, while language production was mainly related to integrity of the left AF. In addition, individual segments of these three tracts were differentially associated with language production and comprehension in aphasia. Our findings highlight the importance of fiber pathways in supporting different language functions and point to the importance of temporal tracts in language processing, in particular, comprehension. Copyright © 2016 Elsevier Ltd. All rights reserved.

White matter pathways and social cognition.

PubMed

Wang, Yin; Metoki, Athanasia; Alm, Kylie H; Olson, Ingrid R

2018-04-20

There is a growing consensus that social cognition and behavior emerge from interactions across distributed regions of the "social brain". Researchers have traditionally focused their attention on functional response properties of these gray matter networks and neglected the vital role of white matter connections in establishing such networks and their functions. In this article, we conduct a comprehensive review of prior research on structural connectivity in social neuroscience and highlight the importance of this literature in clarifying brain mechanisms of social cognition. We pay particular attention to three key social processes: face processing, embodied cognition, and theory of mind, and their respective underlying neural networks. To fully identify and characterize the anatomical architecture of these networks, we further implement probabilistic tractography on a large sample of diffusion-weighted imaging data. The combination of an in-depth literature review and the empirical investigation gives us an unprecedented, well-defined landscape of white matter pathways underlying major social brain networks. Finally, we discuss current problems in the field, outline suggestions for best practice in diffusion-imaging data collection and analysis, and offer new directions for future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis

PubMed Central

Miura, Akiko; Kumabe, Yuri; Kimura, En; Yamashita, Satoshi; Ueda, Akihiko; Hirano, Teruyuki; Uchino, Makoto

2010-01-01

Adult-onset metachromatic leukodystrophy (MLD) often shows schizophrenia- or encephalopathy-like symptoms at an early stage, such as behavioural abnormalities, cognitive impairment, mood disorders and hallucinations. The authors report the case of an adult woman with MLD who had been given antipsychotic medication for schizophrenia. In the differential diagnosis, screening of auto-antibodies was important for ruling out other encephalopathies as she had a euthyroid Hashimoto thyroiditis. Diagnosis was based the results of MRI, nerve conduction velocity, sensory evoked potential, motor evoked potential, lysosomal enzyme activity and gene analysis studies. Brain MRI showed diffuse demyelination spreading from the deep white matter to subcortical area as high signals at the edges of these lesions in diffusion and apparent diffusion coefficient-map images with the U-fibres conserved. The authors diagnosed adult-onset MLD coexisting with euthyroid autoimmune Hashimoto thyroiditis. PMID:22798296

White matter pathology in ALS and lower motor neuron ALS variants: a diffusion tensor imaging study using tract-based spatial statistics.

PubMed

Prudlo, Johannes; Bißbort, Charlotte; Glass, Aenne; Grossmann, Annette; Hauenstein, Karlheinz; Benecke, Reiner; Teipel, Stefan J

2012-09-01

The aim of this work was to investigate white-matter microstructural changes within and outside the corticospinal tract in classical amyotrophic lateral sclerosis (ALS) and in lower motor neuron (LMN) ALS variants by means of diffusion tensor imaging (DTI). We investigated 22 ALS patients and 21 age-matched controls utilizing a whole-brain approach with a 1.5-T scanner for DTI. The patient group was comprised of 15 classical ALS- and seven LMN ALS-variant patients (progressive muscular atrophy, flail arm and flail leg syndrome). Disease severity was measured by the revised version of the functional rating scale. White matter fractional anisotropy (FA) was assessed using tract-based spatial statistics (TBSS) and a region of interest (ROI) approach. We found significant FA reductions in motor and extra-motor cerebral fiber tracts in classical ALS and in the LMN ALS-variant patients compared to controls. The voxel-based TBSS results were confirmed by the ROI findings. The white matter damage correlated with the disease severity in the patient group and was found in a similar distribution, but to a lesser extent, among the LMN ALS-variant subgroup. ALS and LMN ALS variants are multisystem degenerations. DTI shows the potential to determine an earlier diagnosis, particularly in LMN ALS variants. The statistically identical findings of white matter lesions in classical ALS and LMN variants as ascertained by DTI further underline that these variants should be regarded as part of the ALS spectrum.

White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging

PubMed Central

Jung, Rex E.; Grazioplene, Rachael; Caprihan, Arvind; Chavez, Robert S.; Haier, Richard J.

2010-01-01

That creativity and psychopathology are somehow linked remains a popular but controversial idea in neuroscience research. Brain regions implicated in both psychosis-proneness and creative cognition include frontal projection zones and association fibers. In normal subjects, we have previously demonstrated that a composite measure of divergent thinking (DT) ability exhibited significant inverse relationships in frontal lobe areas with both cortical thickness and metabolite concentration of N-acetyl-aspartate (NAA). These findings support the idea that creativity may reside upon a continuum with psychopathology. Here we examine whether white matter integrity, assessed by Fractional Anisotropy (FA), is related to two measures of creativity (Divergent Thinking and Openness to Experience). Based on previous findings, we hypothesize inverse correlations within fronto-striatal circuits. Seventy-two healthy, young adult (18–29 years) subjects were scanned on a 3 Tesla scanner with Diffusion Tensor Imaging. DT measures were scored by four raters (α = .81) using the Consensual Assessment Technique, from which a composite creativity index (CCI) was derived. We found that the CCI was significantly inversely related to FA within the left inferior frontal white matter (t = 5.36, p = .01), and Openness was inversely related to FA within the right inferior frontal white matter (t = 4.61, p = .04). These findings demonstrate an apparent overlap in specific white matter architecture underlying the normal variance of divergent thinking, openness, and psychotic-spectrum traits, consistent with the idea of a continuum. PMID:20339554

Prenatal exposure to maternal and paternal depressive symptoms and white matter microstructure in children.

PubMed

El Marroun, Hanan; Zou, Runyu; Muetzel, Ryan L; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Tiemeier, Henning

2018-04-01

Prenatal maternal depression has been associated with multiple problems in offspring involving affect, cognition, and neuroendocrine functioning. This suggests that prenatal depression influences neurodevelopment. However, the underlying neurodevelopmental mechanism remains unclear. We prospectively assessed whether maternal depressive symptoms during pregnancy and at the child's age 3 years are related to white matter microstructure in 690 children. The association of paternal depressive symptoms with childhood white matter microstructure was assessed to evaluate genetic or familial confounding. Parental depressive symptoms were measured using the Brief Symptom Inventory. In children aged 6-9 years, we used diffusion tensor imaging to assess white matter microstructure characteristics including fractional anisotropy (FA) and mean diffusivity (MD). Exposure to maternal depressive symptoms during pregnancy was associated with higher MD in the uncinate fasciculus and to lower FA and higher MD in the cingulum bundle. No associations of maternal depressive symptoms at the child's age of 3 years with white matter characteristics were observed. Paternal depressive symptoms also showed a trend toward significance for a lower FA in the cingulum bundle. Prenatal maternal depressive symptoms were associated with higher MD in the uncinate fasciculus and the cingulum bundle. These structures are part of the limbic system, which is involved in motivation, emotion, learning, and memory. As paternal depressive symptoms were also related to lower FA in the cingulum, the observed effect may partly reflect a genetic predisposition and shared environmental family factors and to a lesser extent a specific intrauterine effect. © 2018 Wiley Periodicals, Inc.

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

PubMed Central

Provenzale, James M.; Nestrasil, Igor; Chen, Steven; Kan, Shih-hsin; Le, Steven Q.; Jens, Jacqueline K.; Snella, Elizabeth M.; Vondrak, Kristen N.; Yee, Jennifer K.; Vite, Charles H.; Elashoff, David; Duan, Lewei; Wang, Raymond Y.; Ellinwood, N. Matthew; Guzman, Miguel A.; Shapiro, Elsa G.; Dickson, Patricia I.

2015-01-01

Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus.

PubMed

Del Bigio, Marc R; Slobodian, Ili; Schellenberg, Angela E; Buist, Richard J; Kemp-Buors, Tanya L

2011-08-11

Hydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR) imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB) permeability would be detected. Hydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2) and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA) tracer and microscopically by detection of fluorescent dextran conjugates. In nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers. MR characteristics cannot be used as direct surrogates for water content in the immature rat model of hydrocephalus, probably because they are also influenced by other changes in tissue composition that occur during brain maturation. There is no evidence for widespread persistent opening of BBB as a consequence of hydrocephalus in young rats. However, increase in focal BBB permeability suggests that periventricular blood vessels may be disrupted.

White Matter Maturation Supports the Development of Reasoning Ability Through its Influence on Processing Speed

PubMed Central

Ferrer, E.; Whitaker, K.J.; Steele, J.; Green, C.T.; Wendelken, C.; Bunge, S.A.

2013-01-01

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability. PMID:24118718

Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat.

PubMed

Bowman, Elizabeth A; Velakoulis, Dennis; Desmond, Patricia; Walterfang, Mark

2018-01-01

Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.

Structural changes in white matter are uniquely related to children’s reading development

PubMed Central

Myers, Chelsea A.; Vandermosten, Maaike; Farris, Emily A.; Hancock, Roeland; Gimenez, Paul; Black, Jessica M.; Casto, Brandi; Drahos, Miroslav; Tumber, Mandeep; Hendren, Robert L.; Hulme, Charles; Hoeft, Fumiko

2014-01-01

This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at the latter time point. Structural MRI measurements indicated that increases in volume of two left temporo-parietal white matter clusters are unique predictors of reading outcome at Grade 3. Using diffusion MRI, the larger of these two clusters was identified as a location where fibers of the long segment of arcuate fasciculus and superior corona radiata intersect, and the smaller cluster as the posterior arcuate fasciculus. Bias-free regression analyses using regions-of-interest from prior literature revealed white matter volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. PMID:25212581

Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.

PubMed

Boss, H Myrthe; Van Schaik, Sander M; Witkamp, Theo D; Geerlings, Mirjam I; Weinstein, Henry C; Van den Berg-Vos, Renske M

2017-10-01

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

Development of a Human Brain Diffusion Tensor Template

PubMed Central

Peng, Huiling; Orlichenko, Anton; Dawe, Robert J.; Agam, Gady; Zhang, Shengwei; Arfanakis, Konstantinos

2009-01-01

The development of a brain template for diffusion tensor imaging (DTI) is crucial for comparisons of neuronal structural integrity and brain connectivity across populations, as well as for the development of a white matter atlas. Previous efforts to produce a DTI brain template have been compromised by factors related to image quality, the effectiveness of the image registration approach, the appropriateness of subject inclusion criteria, the completeness and accuracy of the information summarized in the final template. The purpose of this work was to develop a DTI human brain template using techniques that address the shortcomings of previous efforts. Therefore, data containing minimal artifacts were first obtained on 67 healthy human subjects selected from an age-group with relatively similar diffusion characteristics (20–40 years of age), using an appropriate DTI acquisition protocol. Non-linear image registration based on mean diffusion-weighted and fractional anisotropy images was employed. DTI brain templates containing median and mean tensors were produced in ICBM-152 space and made publicly available. The resulting set of DTI templates is characterized by higher image sharpness, provides the ability to distinguish smaller white matter fiber structures, contains fewer image artifacts, than previously developed templates, and to our knowledge, is one of only two templates produced based on a relatively large number of subjects. Furthermore, median tensors were shown to better preserve the diffusion characteristics at the group level than mean tensors. Finally, white matter fiber tractography was applied on the template and several fiber-bundles were traced. PMID:19341801

Development of a human brain diffusion tensor template.

PubMed

Peng, Huiling; Orlichenko, Anton; Dawe, Robert J; Agam, Gady; Zhang, Shengwei; Arfanakis, Konstantinos

2009-07-15

The development of a brain template for diffusion tensor imaging (DTI) is crucial for comparisons of neuronal structural integrity and brain connectivity across populations, as well as for the development of a white matter atlas. Previous efforts to produce a DTI brain template have been compromised by factors related to image quality, the effectiveness of the image registration approach, the appropriateness of subject inclusion criteria, and the completeness and accuracy of the information summarized in the final template. The purpose of this work was to develop a DTI human brain template using techniques that address the shortcomings of previous efforts. Therefore, data containing minimal artifacts were first obtained on 67 healthy human subjects selected from an age-group with relatively similar diffusion characteristics (20-40 years of age), using an appropriate DTI acquisition protocol. Non-linear image registration based on mean diffusion-weighted and fractional anisotropy images was employed. DTI brain templates containing median and mean tensors were produced in ICBM-152 space and made publicly available. The resulting set of DTI templates is characterized by higher image sharpness, provides the ability to distinguish smaller white matter fiber structures, contains fewer image artifacts, than previously developed templates, and to our knowledge, is one of only two templates produced based on a relatively large number of subjects. Furthermore, median tensors were shown to better preserve the diffusion characteristics at the group level than mean tensors. Finally, white matter fiber tractography was applied on the template and several fiber-bundles were traced.

Fiberprint: A subject fingerprint based on sparse code pooling for white matter fiber analysis.

PubMed

Kumar, Kuldeep; Desrosiers, Christian; Siddiqi, Kaleem; Colliot, Olivier; Toews, Matthew

2017-09-01

White matter characterization studies use the information provided by diffusion magnetic resonance imaging (dMRI) to draw cross-population inferences. However, the structure, function, and white matter geometry vary across individuals. Here, we propose a subject fingerprint, called Fiberprint, to quantify the individual uniqueness in white matter geometry using fiber trajectories. We learn a sparse coding representation for fiber trajectories by mapping them to a common space defined by a dictionary. A subject fingerprint is then generated by applying a pooling function for each bundle, thus providing a vector of bundle-wise features describing a particular subject's white matter geometry. These features encode unique properties of fiber trajectories, such as their density along prominent bundles. An analysis of data from 861 Human Connectome Project subjects reveals that a fingerprint based on approximately 3000 fiber trajectories can uniquely identify exemplars from the same individual. We also use fingerprints for twin/sibling identification, our observations consistent with the twin data studies of white matter integrity. Our results demonstrate that the proposed Fiberprint can effectively capture the variability in white matter fiber geometry across individuals, using a compact feature vector (dimension of 50), making this framework particularly attractive for handling large datasets. Copyright © 2017 Elsevier Inc. All rights reserved.

Alterations in Cortical Thickness and White Matter Integrity in Mild Cognitive Impairment Measured by Whole Brain Cortical Thickness Mapping and Diffusion Tensor Imaging

PubMed Central

Wang, Liya; Goldstein, Felicia C.; Veledar, Emir; Levey, Allan I.; Lah, James J.; Meltzer, Carolyn C.; Holder, Chad A.; Mao, Hui

2010-01-01

Background and Purpose Mild cognitive impairment (MCI) is a risk factor for Alzheimer's disease (AD) and can be difficult to diagnose due to the subtlety of symptoms. This work attempted to examine gray and white matter changes with cortical thickness analysis and diffusion tensor imaging (DTI) in MCI patients and demographically-matched comparison subjects in order to test these measurements as possible imaging markers for diagnosis. Materials and Methods Subjects with amnestic MCI (n=10; age 72.2±7.1) and normal cognition (n=10; age 70.1±7.7) underwent DTI and T1 weighted MRI at 3T. Fractional anisotropy, apparent diffusion coefficient and cortical thickness were measured and compared between MCI and control groups. The diagnostic accuracy of two methods, either in combination or separately, was evaluated using binary logistic regression and nonparametric statistical analyses for sensitivity, specificity and accuracy. Results Decreased FA and increased ADC in white matter regions of frontal and temporal lobes and corpus callosum were observed in MCI patients. Cortical thickness was decreased in gray matter regions of the frontal, temporal, parietal lobes in MCI patients. Changes in white matter and cortical thickness appeared to be more pronounced in the left hemisphere than in the right hemisphere. Furthermore the combination of cortical thickness and DTI measurements in left temporal areas improved the accuracy of differentiating MCI patients from controls compared to either measure alone. Conclusion DTI and cortical thickness analyses may both serve imaging markers for differentiating MCI from normal aging. Combined use of two methods may improve the accuracy of MCI diagnosis. PMID:19279272

Leading non-Gaussian corrections for diffusion orientation distribution function.

PubMed

Jensen, Jens H; Helpern, Joseph A; Tabesh, Ali

2014-02-01

An analytical representation of the leading non-Gaussian corrections for a class of diffusion orientation distribution functions (dODFs) is presented. This formula is constructed from the diffusion and diffusional kurtosis tensors, both of which may be estimated with diffusional kurtosis imaging (DKI). By incorporating model-independent non-Gaussian diffusion effects, it improves on the Gaussian approximation used in diffusion tensor imaging (DTI). This analytical representation therefore provides a natural foundation for DKI-based white matter fiber tractography, which has potential advantages over conventional DTI-based fiber tractography in generating more accurate predictions for the orientations of fiber bundles and in being able to directly resolve intra-voxel fiber crossings. The formula is illustrated with numerical simulations for a two-compartment model of fiber crossings and for human brain data. These results indicate that the inclusion of the leading non-Gaussian corrections can significantly affect fiber tractography in white matter regions, such as the centrum semiovale, where fiber crossings are common. 2013 John Wiley & Sons, Ltd.

Leading Non-Gaussian Corrections for Diffusion Orientation Distribution Function

PubMed Central

Jensen, Jens H.; Helpern, Joseph A.; Tabesh, Ali

2014-01-01

An analytical representation of the leading non-Gaussian corrections for a class of diffusion orientation distribution functions (dODFs) is presented. This formula is constructed out of the diffusion and diffusional kurtosis tensors, both of which may be estimated with diffusional kurtosis imaging (DKI). By incorporating model-independent non-Gaussian diffusion effects, it improves upon the Gaussian approximation used in diffusion tensor imaging (DTI). This analytical representation therefore provides a natural foundation for DKI-based white matter fiber tractography, which has potential advantages over conventional DTI-based fiber tractography in generating more accurate predictions for the orientations of fiber bundles and in being able to directly resolve intra-voxel fiber crossings. The formula is illustrated with numerical simulations for a two-compartment model of fiber crossings and for human brain data. These results indicate that the inclusion of the leading non-Gaussian corrections can significantly affect fiber tractography in white matter regions, such as the centrum semiovale, where fiber crossings are common. PMID:24738143

Mapping of ApoE4 related white matter damage using diffusion MRI

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Gajawelli, Niharika; Hwang, Darryl H.; Kriger, Stephen; Law, Meng; Chui, Helena; Weiner, Michael; Lepore, Natasha

2014-04-01

ApoliopoproteinE Ɛ4 (ApoE-Ɛ4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE 4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Aβ. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-Ɛ4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE Ɛ4 allele. We found potentially significant regions (Puncorrected < 0:05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).

Decreased white matter integrity in fronto-occipital fasciculus bundles: relation to visual information processing in alcohol-dependent subjects.

PubMed

Bagga, Deepika; Sharma, Aakansha; Kumari, Archana; Kaur, Prabhjot; Bhattacharya, Debajyoti; Garg, Mohan Lal; Khushu, Subash; Singh, Namita

2014-02-01

Chronic alcohol abuse is characterized by impaired cognitive abilities with a more severe deficit in visual than in verbal functions. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The present study sought to increase current understanding of the impairment of visual processing abilities in alcohol-dependent subjects, and its correlation with white matter microstructural alterations, using diffusion tensor imaging (DTI). To that end, a DTI study was carried out on 35 alcohol-dependent subjects and 30 healthy male control subjects. Neuropsychological tests were assessed for visual processing skills and deficits were reported as raw dysfunction scores (rDyS). Reduced FA (fractional anisotropy) and increased MD (mean diffusivity) were observed bilaterally in inferior and superior fronto-occipital fasciculus (FOF) fiber bundles. A significant inverse correlation in rDyS and FA values was observed in these fiber tracts whereas a positive correlation of these scores was found with the MD values. Our results suggest that FOF fiber bundles linking the frontal lobe to occipital lobe might be related to visual processing skills. This is the first report of an alteration of the white matter microstructure of FOF fiber bundles that might have functional consequences for visual processing in alcohol-dependent subjects who exhibit no neurological complications. Copyright © 2014 Elsevier Inc. All rights reserved.

Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

PubMed

Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

2014-12-01

In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

In Vivo Evaluation of White Matter Integrity and Anterograde Transport in Visual System After Excitotoxic Retinal Injury With Multimodal MRI and OCT

PubMed Central

Ho, Leon C.; Wang, Bo; Conner, Ian P.; van der Merwe, Yolandi; Bilonick, Richard A.; Kim, Seong-Gi; Wu, Ed X.; Sigal, Ian A.; Wollstein, Gadi; Schuman, Joel S.; Chan, Kevin C.

2015-01-01

Purpose. Excitotoxicity has been linked to the pathogenesis of ocular diseases and injuries and may involve early degeneration of both anterior and posterior visual pathways. However, their spatiotemporal relationships remain unclear. We hypothesized that the effects of excitotoxic retinal injury (ERI) on the visual system can be revealed in vivo by diffusion tensor magnetic resonance imagining (DTI), manganese-enhanced magnetic resonance imagining (MRI), and optical coherence tomography (OCT). Methods. Diffusion tensor MRI was performed at 9.4 Tesla to monitor white matter integrity changes after unilateral N-methyl-D-aspartate (NMDA)-induced ERI in six Sprague-Dawley rats and six C57BL/6J mice. Additionally, four rats and four mice were intravitreally injected with saline to compare with NMDA-injected animals. Optical coherence tomography of the retina and manganese-enhanced MRI of anterograde transport were evaluated and correlated with DTI parameters. Results. In the rat optic nerve, the largest axial diffusivity decrease and radial diffusivity increase occurred within the first 3 and 7 days post ERI, respectively, suggestive of early axonal degeneration and delayed demyelination. The optic tract showed smaller directional diffusivity changes and weaker DTI correlations with retinal thickness compared with optic nerve, indicative of anterograde degeneration. The splenium of corpus callosum was also reorganized at 4 weeks post ERI. The DTI profiles appeared comparable between rat and mouse models. Furthermore, the NMDA-injured visual pathway showed reduced anterograde manganese transport, which correlated with diffusivity changes along but not perpendicular to optic nerve. Conclusions. Diffusion tensor MRI, manganese-enhanced MRI, and OCT provided an in vivo model system for characterizing the spatiotemporal changes in white matter integrity, the eye–brain relationships and structural–physiological relationships in the visual system after ERI. PMID:26066747

Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Christopher H., E-mail: chchap@umich.edu; Nagesh, Vijaya; Sundgren, Pia C.

Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results:more » In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.« less

Recovery of White Matter following Pediatric Traumatic Brain Injury Depends on Injury Severity.

PubMed

Genc, Sila; Anderson, Vicki; Ryan, Nicholas P; Malpas, Charles B; Catroppa, Cathy; Beauchamp, Miriam H; Silk, Timothy J

2017-02-15

Previous studies in pediatric traumatic brain injury (TBI) have been variable in describing the effects of injury severity on white-matter development. The present study used diffusion tensor imaging to investigate prospective sub-acute and longitudinal relationships between early clinical indicators of injury severity, diffusion metrics, and neuropsychological outcomes. Pediatric patients with TBI underwent magnetic resonance imaging (MRI) (n = 78, mean [M] = 10.56, standard deviation [SD] = 2.21 years) at the sub-acute stage after injury (M = 5.55, SD = 3.05 weeks), and typically developing children were also included and imaged (n = 30, M = 10.60, SD = 2.88 years). A sub-set of the patients with TBI (n = 15) was followed up with MRI 2 years post-injury. Diffusion MRI images were acquired at sub-acute and 2-year follow-up time points and analyzed using Tract-Based Spatial Statistics. At the sub-acute stage, mean diffusivity and axial diffusivity were significantly higher in the TBI group compared with matched controls (p < 0.05). TBI severity significantly predicted diffusion profiles at the sub-acute and 2-year post-injury MRI. Patients with more severe TBI also exhibited poorer information processing speed at 6-months post-injury, which in turn correlated with their diffusion metrics. These findings highlight that the severity of the injury not only has an impact on white-matter microstructure, it also impacts its recovery over time. Moreover, findings suggest that sub-acute microstructural changes may represent a useful prognostic marker to identify children at elevated risk for longer term deficits.

Fully-integrated framework for the segmentation and registration of the spinal cord white and gray matter.

PubMed

Dupont, Sara M; De Leener, Benjamin; Taso, Manuel; Le Troter, Arnaud; Nadeau, Sylvie; Stikov, Nikola; Callot, Virginie; Cohen-Adad, Julien

2017-04-15

The spinal cord white and gray matter can be affected by various pathologies such as multiple sclerosis, amyotrophic lateral sclerosis or trauma. Being able to precisely segment the white and gray matter could help with MR image analysis and hence be useful in further understanding these pathologies, and helping with diagnosis/prognosis and drug development. Up to date, white/gray matter segmentation has mostly been done manually, which is time consuming, induces a bias related to the rater and prevents large-scale multi-center studies. Recently, few methods have been proposed to automatically segment the spinal cord white and gray matter. However, no single method exists that combines the following criteria: (i) fully automatic, (ii) works on various MRI contrasts, (iii) robust towards pathology and (iv) freely available and open source. In this study we propose a multi-atlas based method for the segmentation of the spinal cord white and gray matter that addresses the previous limitations. Moreover, to study the spinal cord morphology, atlas-based approaches are increasingly used. These approaches rely on the registration of a spinal cord template to an MR image, however the registration usually doesn't take into account the spinal cord internal structure and thus lacks accuracy. In this study, we propose a new template registration framework that integrates the white and gray matter segmentation to account for the specific gray matter shape of each individual subject. Validation of segmentation was performed in 24 healthy subjects using T 2 * -weighted images, in 8 healthy subjects using diffusion weighted images (exhibiting inverted white-to-gray matter contrast compared to T 2 *-weighted), and in 5 patients with spinal cord injury. The template registration was validated in 24 subjects using T 2 *-weighted data. Results of automatic segmentation on T 2 *-weighted images was in close correspondence with the manual segmentation (Dice coefficient in the white/gray matter of 0.91/0.71 respectively). Similarly, good results were obtained in data with inverted contrast (diffusion-weighted image) and in patients. When compared to the classical template registration framework, the proposed framework that accounts for gray matter shape significantly improved the quality of the registration (comparing Dice coefficient in gray matter: p=9.5×10 -6 ). While further validation is needed to show the benefits of the new registration framework in large cohorts and in a variety of patients, this study provides a fully-integrated tool for quantitative assessment of white/gray matter morphometry and template-based analysis. All the proposed methods are implemented in the Spinal Cord Toolbox (SCT), an open-source software for processing spinal cord multi-parametric MRI data. Copyright © 2017 Elsevier Inc. All rights reserved.

9 CFR 590.510 - Classifications of shell eggs used in the processing of egg products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... to include black rots, white rots, mixed rots, green whites, eggs with diffused blood in the albumen... any other filthy and decomposed eggs including the following: (1) Any egg with visible foreign matter...

9 CFR 590.510 - Classifications of shell eggs used in the processing of egg products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... to include black rots, white rots, mixed rots, green whites, eggs with diffused blood in the albumen... any other filthy and decomposed eggs including the following: (1) Any egg with visible foreign matter...

Left-Hemispheric Microstructural Abnormalities in Children With High Functioning Autism Spectrum Disorder

PubMed Central

Peterson, Daniel; Mahajan, Rajneesh; Crocetti, Deana; Mejia, Amanda; Mostofsky, Stewart

2014-01-01

Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. PMID:25256103

The effects of puberty on white matter development in boys.

PubMed

Menzies, Lara; Goddings, Anne-Lise; Whitaker, Kirstie J; Blakemore, Sarah-Jayne; Viner, Russell M

2015-02-01

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7-16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n=22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n=39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty×age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effects of puberty on white matter development in boys

PubMed Central

Menzies, Lara; Goddings, Anne-Lise; Whitaker, Kirstie J.; Blakemore, Sarah-Jayne; Viner, Russell M.

2015-01-01

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7–16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n = 39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty × age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone. PMID:25454416

White matter tractography by means of Turboprop diffusion tensor imaging.

PubMed

Arfanakis, Konstantinos; Gui, Minzhi; Lazar, Mariana

2005-12-01

White matter fiber-tractography by means of diffusion tensor imaging (DTI) is a noninvasive technique that provides estimates of the structural connectivity of the brain. However, conventional fiber-tracking methods using DTI are based on echo-planar image acquisitions (EPI), which suffer from image distortions and artifacts due to magnetic susceptibility variations and eddy currents. Thus, a large percentage of white matter fiber bundles that are mapped using EPI-based DTI data are distorted, and/or terminated early, while others are completely undetected. This severely limits the potential of fiber-tracking techniques. In contrast, Turboprop imaging is a multiple-shot gradient and spin-echo (GRASE) technique that provides images with significantly fewer susceptibility and eddy current-related artifacts than EPI. The purpose of this work was to evaluate the performance of fiber-tractography techniques when using data obtained with Turboprop-DTI. All fiber pathways that were mapped were found to be in agreement with the anatomy. There were no visible distortions in any of the traced fiber bundles, even when these were located in the vicinity of significant magnetic field inhomogeneities. Additionally, the Turboprop-DTI data used in this research were acquired in less than 19 min of scan time. Thus, Turboprop appears to be a promising DTI data acquisition technique for tracing white matter fibers.

Longitudinal changes in white matter microstructure after heavy cannabis use

PubMed Central

Becker, Mary P.; Collins, Paul F.; Lim, Kelvin O.; Muetzel, R.L.; Luciana, M.

2015-01-01

Diffusion tensor imaging (DTI) studies of cannabis users report alterations in brain white matter microstructure, primarily based on cross-sectional research, and etiology of the alterations remains unclear. We report findings from longitudinal voxelwise analyses of DTI data collected at baseline and at a 2-year follow-up on 23 young adult (18-20 years old at baseline) regular cannabis users and 23 age-, sex-, and IQ-matched non-using controls with limited substance use histories. Onset of cannabis use was prior to age 17. Cannabis users displayed reduced longitudinal growth in fractional anisotropy in the central and parietal regions of the right and left superior longitudinal fasciculus, in white matter adjacent to the left superior frontal gyrus, in the left corticospinal tract, and in the right anterior thalamic radiation lateral to the genu of the corpus callosum, along with less longitudinal reduction of radial diffusion in the right central/posterior superior longitudinal fasciculus, corticospinal tract, and posterior cingulum. Greater amounts of cannabis use were correlated with reduced longitudinal growth in FA as was relatively impaired performance on a measure of verbal learning. These findings suggest that continued heavy cannabis use during adolescence and young adulthood alters ongoing development of white matter microstructure, contributing to functional impairment. PMID:26602958

Can musical training influence brain connectivity? Evidence from diffusion tensor MRI.

PubMed

Moore, Emma; Schaefer, Rebecca S; Bastin, Mark E; Roberts, Neil; Overy, Katie

2014-06-10

In recent years, musicians have been increasingly recruited to investigate grey and white matter neuroplasticity induced by skill acquisition. The development of Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) has allowed more detailed investigation of white matter connections within the brain, addressing questions about the effect of musical training on connectivity between specific brain regions. Here, current DT-MRI analysis techniques are discussed and the available evidence from DT-MRI studies into differences in white matter architecture between musicians and non-musicians is reviewed. Collectively, the existing literature tends to support the hypothesis that musical training can induce changes in cross-hemispheric connections, with significant differences frequently reported in various regions of the corpus callosum of musicians compared with non-musicians. However, differences found in intra-hemispheric fibres have not always been replicated, while findings regarding the internal capsule and corticospinal tracts appear to be contradictory. There is also recent evidence to suggest that variances in white matter structure in non-musicians may correlate with their ability to learn musical skills, offering an alternative explanation for the structural differences observed between musicians and non-musicians. Considering the inconsistencies in the current literature, possible reasons for conflicting results are offered, along with suggestions for future research in this area.

Variations in the neurobiology of reading in children and adolescents born full term and preterm

PubMed Central

Travis, Katherine E.; Ben-Shachar, Michal; Myall, Nathaniel J.; Feldman, Heidi M.

2016-01-01

Diffusion properties of white matter tracts have been associated with individual differences in reading. Individuals born preterm are at risk of injury to white matter. In this study we compared the associations between diffusion properties of white matter and reading skills in children and adolescents born full term and preterm. 45 participants, aged 9–17 years, included 26 preterms (born < 36 weeks' gestation) and 19 full-terms. Tract fractional anisotropy (FA) profiles were generated for five bilateral white matter tracts previously associated with reading: anterior superior longitudinal fasciculus (aSLF), arcuate fasciculus (Arc), corticospinal tract (CST), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). Mean scores on reading for the two groups were in the normal range and were not statistically different. In both groups, FA was associated with measures of single word reading and comprehension in the aSLF, AF, CST, and UF. However, correlations were negative in the full term group and positive in the preterm group. These results demonstrate variations in the neurobiology of reading in children born full term and preterm despite comparable reading skills. Findings suggest that efficient information exchange required for strong reading abilities may be accomplished via a different balance of neurobiological mechanisms in different groups of readers. PMID:27158588

Development of white matter microstructure in relation to verbal and visuospatial working memory—A longitudinal study

PubMed Central

Fjell, Anders M.; Tamnes, Christian K.; Grydeland, Håkon; Due-Tønnessen, Paulina; Bjørnerud, Atle; Sampaio-Baptista, Cassandra; Andersson, Jesper; Johansen-Berg, Heidi; Walhovd, Kristine B.

2018-01-01

Working memory capacity is pivotal for a broad specter of cognitive tasks and develops throughout childhood. This must in part rely on development of neural connections and white matter microstructure maturation, but there is scarce knowledge of specific relations between this and different aspects of working memory. Diffusion tensor imaging (DTI) enables us to study development of brain white matter microstructure. In a longitudinal DTI study of 148 healthy children between 4 and 11 years scanned twice with an on average 1.6 years interval, we characterized change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD) in 10 major white matter tracts hypothesized to be of importance for working memory. The results showed relationships between change in several tracts and change in visuospatial working memory. Specifically, improvement in visuospatial working memory capacity was significantly associated with decreased MD, RD and AD in inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in the right hemisphere, as well as forceps major (FMaj). No significant relationships were found between change in DTI metrics and change in verbal working memory capacity. These findings yield new knowledge about brain development and corresponding working memory improvements in childhood. PMID:29689058

White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study.

PubMed

Ota, Miho; Noda, Takamasa; Sato, Noriko; Hattori, Kotaro; Hori, Hiroaki; Sasayama, Daimei; Teraishi, Toshiya; Nagashima, Anna; Obu, Satoko; Higuchi, Teruhiko; Kunugi, Hiroshi

2015-06-01

The DSM-IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes. Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel-by-voxel basis among the two diagnostic groups and healthy subjects. There were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD. Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.

PubMed

Cole, James H; Farmer, Ruth E; Rees, Elin M; Johnson, Hans J; Frost, Chris; Scahill, Rachael I; Hobbs, Nicola Z

2014-03-21

Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls). T1 data was used to generate further ROIs for analysis in a reduced sample of 18 participants. The results suggest that fractional anisotropy (FA) and other diffusivity metrics are generally highly reliable, with ICCs indicating considerably lower within-subject compared to between-subject variability in both HD patients and controls. Where ICC was low, particularly for the diffusivity measures in the caudate and putamen, this was partly influenced by outliers. The analysis suggests that the specific DTI methods used here are appropriate for cross-sectional research in HD, and give confidence that they can also be applied longitudinally, although this requires further investigation. An important caveat for DTI studies is that test-retest reliability may not be evenly distributed throughout the brain whereby highly anisotropic white matter regions tended to show lower relative within-subject variability than other white or grey matter regions.

Longitudinal changes in white matter integrity among adolescent substance users.

PubMed

Bava, Sunita; Jacobus, Joanna; Thayer, Rachel E; Tapert, Susan F

2013-01-01

The influence of repeated substance use during adolescent neurodevelopment remains unclear as there have been few prospective investigations. The aims of this study were to identify longitudinal changes in fiber tract integrity associated with alcohol- and marijuana-use severity over the course of 1.5 years. Adolescents with extensive marijuana- and alcohol-use histories by mid-adolescence (n = 41) and youth with consistently minimal if any substance use (n = 51) were followed over 18 months. Teens received diffusion tensor imaging and detailed substance-use assessments with toxicology screening at baseline and 18-month follow-ups (i.e., 182 scans in all), as well as interim substance-use interviews each 6 months. At an 18-month follow-up, substance users showed poorer white matter integrity in 7 tracts: (i) right superior longitudinal fasciculus, (ii) left superior longitudinal fasciculus, (iii) right posterior thalamic radiations, (iv) right prefrontal thalamic fibers, (v) right superior temporal gyrus white matter, (vi) right inferior longitudinal fasciculus, and (vii) left posterior corona radiata (ps < 0.01). More alcohol use during the interscan interval predicted higher mean diffusivity (i.e., worsened integrity) in right (p < 0.05) and left (p = 0.06) superior longitudinal fasciculi, above and beyond baseline values in these bundles. Marijuana use during the interscan interval did not predict change over time. More externalizing behaviors at Time 1 predicted lower fractional anisotropy and higher radial diffusivity (i.e., poorer integrity) of the right prefrontal thalamic fibers (p < 0.025). Findings add to previous cross-sectional studies reporting white matter disadvantages in youth with substance-use histories. In particular, alcohol use during adolescent neurodevelopment may be linked to reductions in white matter quality in association fiber tracts with frontal connections. In contrast, youth who engage in a variety of risk-taking behaviors may have unique neurodevelopmental trajectories characterized by truncated development in fronto-thalamic tracts, which could have functional and clinical consequences in young adulthood. Copyright © 2012 by the Research Society on Alcoholism.

Memory binding and white matter integrity in familial Alzheimer’s disease

PubMed Central

Saarimäki, Heini; Bastin, Mark E.; Londoño, Ana C.; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

2015-01-01

Binding information in short-term and long-term memory are functions sensitive to Alzheimer’s disease. They have been found to be affected in patients who meet criteria for familial Alzheimer’s disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer’s disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer’s disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer’s disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer’s disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer’s disease. PMID:25762465

Memory binding and white matter integrity in familial Alzheimer's disease.

PubMed

Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

2015-05-01

Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study.

PubMed

Mengotti, Paola; D'Agostini, Serena; Terlevic, Robert; De Colle, Cristina; Biasizzo, Elsa; Londero, Danielle; Ferro, Adele; Rambaldelli, Gianluca; Balestrieri, Matteo; Zanini, Sergio; Fabbro, Franco; Molteni, Massimo; Brambilla, Paolo

2011-02-01

A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. Twenty children with autism (mean age= 7 ± 2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values. Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits. Copyright © 2010 Elsevier Inc. All rights reserved.

Abnormal white matter properties in adolescent girls with anorexia nervosa

PubMed Central

Travis, Katherine E.; Golden, Neville H.; Feldman, Heidi M.; Solomon, Murray; Nguyen, Jenny; Mezer, Aviv; Yeatman, Jason D.; Dougherty, Robert F.

2015-01-01

Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN. PMID:26740918

Abnormalities in white matter microstructure associated with chronic ketamine use.

PubMed

Edward Roberts, R; Curran, H Valerie; Friston, Karl J; Morgan, Celia J A

2014-01-01

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use-on brain structure in humans-remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences. These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use.

White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning

PubMed Central

Fan, Jia; Meintjes, Ernesta M.; Molteno, Christopher D.; Spottiswoode, Bruce S.; Dodge, Neil C.; Alhamud, Alkathafi A.; Stanton, Mark E.; Peterson, Bradley S.; Jacobson, Joseph L.; Jacobson, Sandra W.

2015-01-01

Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1±1.0 yrs, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles. PMID:25783559

Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.

PubMed

Pettit, Lewis D; Bastin, Mark E; Smith, Colin; Bak, Thomas H; Gillingwater, Thomas H; Abrahams, Sharon

2013-11-01

Cognitive impairment in amyotrophic lateral sclerosis is characterized by deficits on tests of executive function; however, the contribution of abnormal processing speed is unknown. Methods are confounded by tasks that depend on motor speed in patients with physical disability. Structural and functional magnetic resonance imaging studies have revealed multi-system cerebral involvement, with evidence of reduced white matter volume and integrity in predominant frontotemporal regions. The current study has two aims. First, to investigate whether cognitive impairments in amyotrophic lateral sclerosis are due to executive dysfunction or slowed processing speed using methodology that accommodates motor disability. This is achieved using a dual-task paradigm and tasks that manipulate stimulus presentation times and do not rely on response motor speed. Second, to identify relationships between specific cognitive impairments and the integrity of distinct white matter tracts. Thirty patients with amyotrophic lateral sclerosis and 30 age- and education-matched control subjects were administered an experimental dual-task procedure that combined a visual inspection time task and digit recall. In addition, measures of executive function (including letter fluency) and processing speed (visual inspection time and rapid serial letter identification) were administered. Integrity of white matter tracts was determined using region of interest analyses of diffusion tensor magnetic resonance imaging data. Patients with amyotrophic lateral sclerosis did not show impairments on tests of processing speed, but executive deficits were revealed once visual inspection time was combined with digit recall (dual-task) and in letter fluency. In addition to the corticospinal tracts, significant differences in fractional anisotropy and mean diffusivity were found between groups in a number of prefrontal and temporal white matter tracts including the anterior cingulate, anterior thalamic radiation, uncinate fasciculus and hippocampal portion of the cingulum bundles. Significant differences also emerged in the anterior corona radiata as well as in white matter underlying the superior, medial and inferior frontal gyri and the temporal gyri. Dual-task performance significantly correlated with fractional anisotropy measures in the middle frontal gyrus white matter and anterior corona radiata. Letter fluency indices significantly correlated with fractional anisotropy measures of the inferior frontal gyrus white matter and corpus callosum in addition to the corticospinal tracts and mean diffusivity measures in the white matter of the superior frontal gyrus. The current study demonstrates that cognitive impairment in amyotrophic lateral sclerosis is not due to generic slowing of processing speed. Moreover, different executive deficits are related to distinct prefrontal tract involvement in amyotrophic lateral sclerosis with dual-task impairment associating with dorsolateral prefrontal dysfunction and letter fluency showing greater dependence on inferolateral prefrontal dysfunction.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

PubMed Central

Baker, Simon T.; Cropley, Vanessa L.; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M.; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T.; Loughland, Carmel; Catts, Stanley V.; Mowry, Bryan; Weickert, Thomas W.; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

2017-01-01

Abstract White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain’s fiber bundles. PMID:27535082

White matter structure changes as adults learn a second language.

PubMed

Schlegel, Alexander A; Rudelson, Justin J; Tse, Peter U

2012-08-01

Traditional models hold that the plastic reorganization of brain structures occurs mainly during childhood and adolescence, leaving adults with limited means to learn new knowledge and skills. Research within the last decade has begun to overturn this belief, documenting changes in the brain's gray and white matter as healthy adults learn simple motor and cognitive skills [Lövdén, M., Bodammer, N. C., Kühn, S., Kaufmann, J., Schütze, H., Tempelmann, C., et al. Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia, 48, 3878-3883, 2010; Taubert, M., Draganski, B., Anwander, A., Müller, K., Horstmann, A., Villringer, A., et al. Dynamic properties of human brain structure: Learning-related changes in cortical areas and associated fiber connections. The Journal of Neuroscience, 30, 11670-11677, 2010; Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. Training induces changes in white-matter architecture. Nature Neuroscience, 12, 1370-1371, 2009; Draganski, B., Gaser, C., Busch, V., Schuirer, G., Bogdahn, U., & May, A. Changes in grey matter induced by training. Nature, 427, 311-312, 2004]. Although the significance of these changes is not fully understood, they reveal a brain that remains plastic well beyond early developmental periods. Here we investigate the role of adult structural plasticity in the complex, long-term learning process of foreign language acquisition. We collected monthly diffusion tensor imaging scans of 11 English speakers who took a 9-month intensive course in written and spoken Modern Standard Chinese as well as from 16 control participants who did not study a language. We show that white matter reorganizes progressively across multiple sites as adults study a new language. Language learners exhibited progressive changes in white matter tracts associated with traditional left hemisphere language areas and their right hemisphere analogs. Surprisingly, the most significant changes occurred in frontal lobe tracts crossing the genu of the corpus callosum-a region not generally included in current neural models of language processing. These results indicate that plasticity of white matter plays an important role in adult language learning and additionally demonstrate the potential of longitudinal diffusion tensor imaging as a new tool to yield insights into cognitive processes.

Effects of motion and b-matrix correction for high resolution DTI with short-axis PROPELLER-EPI

PubMed Central

Aksoy, Murat; Skare, Stefan; Holdsworth, Samantha; Bammer, Roland

2010-01-01

Short-axis PROPELLER-EPI (SAP-EPI) has been proven to be very effective in providing high-resolution diffusion-weighted and diffusion tensor data. The self-navigation capabilities of SAP-EPI allow one to correct for motion, phase errors, and geometric distortion. However, in the presence of patient motion, the change in the effective diffusion-encoding direction (i.e. the b-matrix) between successive PROPELLER ‘blades’ can decrease the accuracy of the estimated diffusion tensors, which might result in erroneous reconstruction of white matter tracts in the brain. In this study, we investigate the effects of alterations in the b-matrix as a result of patient motion on the example of SAP-EPI DTI and eliminate these effects by incorporating our novel single-step non-linear diffusion tensor estimation scheme into the SAP-EPI post-processing procedure. Our simulations and in-vivo studies showed that, in the presence of patient motion, correcting the b-matrix is necessary in order to get more accurate diffusion tensor and white matter pathway reconstructions. PMID:20222149

Diffusion MRI and its role in neuropsychology

PubMed Central

Mueller, Bryon A; Lim, Kelvin O; Hemmy, Laura; Camchong, Jazmin

2015-01-01

Diffusion Magnetic Resonance Imaging (dMRI) is a popular method used by neuroscientists to uncover unique information about the structural connections within the brain. dMRI is a non-invasive imaging methodology in which image contrast is based on the diffusion of water molecules in tissue. While applicable to many tissues in the body, this review focuses exclusively on the use of dMRI to examine white matter in the brain. In this review, we begin with a definition of diffusion and how diffusion is measured with MRI. Next we introduce the diffusion tensor model, the predominant model used in dMRI. We then describe acquisition issues related to acquisition parameters and scanner hardware and software. Sources of artifacts are then discussed, followed by a brief review of analysis approaches. We provide an overview of the limitations of the traditional diffusion tensor model, and highlight several more sophisticated non-tensor models that better describe the complex architecture of the brain’s white matter. We then touch on reliability and validity issues of diffusion measurements. Finally, we describe examples of ways in which dMRI has been applied to studies of brain disorders and how identified alterations relate to symptomatology and cognition. PMID:26255305

[From Brownian motion to mind imaging: diffusion MRI].

PubMed

Le Bihan, Denis

2006-11-01

The success of diffusion MRI, which was introduced in the mid 1980s is deeply rooted in the powerful concept that during their random, diffusion-driven movements water molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. The observation of these movements thus provides valuable information on the structure and the geometric organization of tissues. The most successful application of diffusion MRI has been in brain ischemia, following the discovery that water diffusion drops at a very early stage of the ischemic event. Diffusion MRI provides some patients with the opportunity to receive suitable treatment at a very acute stage when brain tissue might still be salvageable. On the other hand, diffusion is modulated by the spatial orientation of large bundles of myelinated axons running in parallel through in brain white matter. This feature can be exploited to map out the orientation in space of the white matter tracks and to visualize the connections between different parts of the brain on an individual basis. Furthermore, recent data suggest that diffusion MRI may also be used to visualize rapid dynamic tissue changes, such as neuronal swelling, associated with cortical activation, offering a new and direct approach to brain functional imaging.

Raymond de Vieussens and his contribution to the study of white matter anatomy: historical vignette.

PubMed

Vergani, Francesco; Morris, Christopher M; Mitchell, Patrick; Duffau, Hugues

2012-12-01

In recent years, there has been a renewed interest in the study of white matter anatomy, both with the use of postmortem dissections and diffusion tensor imaging tractography. One of the precursors in the study of white matter anatomy was Raymond de Vieussens (1641-1716), a French anatomist born in Le Vigan. He studied medicine at the University of Montpellier in southern France, one of the most ancient and lively schools of medicine in Europe. In 1684 Vieussens published his masterpiece, the Neurographia Universalis, which is still considered one of the most complete and accurate descriptions of the nervous system provided in the 17th century. He described the white matter of the centrum ovale and was the first to demonstrate the continuity of the white matter fibers from the centrum ovale to the brainstem. He also described the dentate nuclei, the pyramids, and the olivary nuclei. According to the theory of Galen, Vieussens considered that the function of the white matter was to convey the "animal spirit" from the centrum ovale to the spinal cord. Although neglected, Vieussens' contribution to the study of white matter is relevant. His pioneering work showed that the white matter is not a homogeneous substance, but rather a complex structure rich in fibers that are interconnected with different parts of the brain. These initial results paved the way to advancements observed in later centuries that eventually led to modern hodology.

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

In vivo quantification of demyelination and recovery using compartment-specific diffusion MRI metrics validated by electron microscopy.

PubMed

Jelescu, Ileana O; Zurek, Magdalena; Winters, Kerryanne V; Veraart, Jelle; Rajaratnam, Anjali; Kim, Nathanael S; Babb, James S; Shepherd, Timothy M; Novikov, Dmitry S; Kim, Sungheon G; Fieremans, Els

2016-05-15

There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T2, magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment-specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6weeks) and chronic (12weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T2, magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6-week intoxication produced a significant decrease in axonal water fraction (p<0.001), with only mild changes in extra-axonal radial diffusivity, consistent with patchy demyelination, while a 12-week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p=0.0135), consistent with more severe demyelination and clearance of the extra-axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (ρ=0.66; p=0.0014) but not with the g-ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (ρ=0.48; p=0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter. Copyright © 2016 Elsevier Inc. All rights reserved.

Comprehensive Investigation of White Matter Tracts in Professional Chess Players and Relation to Expertise: Region of Interest and DMRI Connectometry.

PubMed

Mayeli, Mahsa; Rahmani, Farzaneh; Aarabi, Mohammad Hadi

2018-01-01

Purpose: Expertise is the product of training. Few studies have used functional connectivity or conventional diffusometric methods to identify neural underpinnings of chess expertise. Diffusometric variables of white matter might reflect these adaptive changes, along with changes in structural connectivity, which is a sensitive measure of microstructural changes. Method: Diffusometric variables of 29 professional chess players and 29 age-sex matched controls were extracted for white matter regions based on John Hopkin's Mori white matter atlas and partially correlated against professional training time and level of chess proficiency. Diffusion MRI connectometry was implemented to identify changes in structural connectivity in professional players compared to novices. Result: Compared to novices, higher planar anisotropy (CP) was observed in inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) and cingulate gyrus, in professional chess players, which correlated with higher RPM score in this group. Higher fractional anisotropy (FA) was observed in ILF, uncinate fasciculus (UF) and hippocampus and correlated with better scores in Raven's progressive matrices (RPM) score and longer duration of chess training in professional players. Consistently, radial diffusivity in bilateral IFOF, bilateral ILF and bilateral SLF was inversely correlated with level of training in professional players. DMRI connectometry analysis identified increased connectivity in bilateral UF, bilateral IFOF, bilateral cingulum, and corpus callosum in chess player's compared to controls. Conclusion: Structural connectivity of major associational subcortical white matter fibers are increased in professional chess players. FA and CP of ILF, SLF and UF directly correlates with duration of professional training and RPM score, in professional chess players.

Comprehensive Investigation of White Matter Tracts in Professional Chess Players and Relation to Expertise: Region of Interest and DMRI Connectometry

PubMed Central

Mayeli, Mahsa; Rahmani, Farzaneh; Aarabi, Mohammad Hadi

2018-01-01

Purpose: Expertise is the product of training. Few studies have used functional connectivity or conventional diffusometric methods to identify neural underpinnings of chess expertise. Diffusometric variables of white matter might reflect these adaptive changes, along with changes in structural connectivity, which is a sensitive measure of microstructural changes. Method: Diffusometric variables of 29 professional chess players and 29 age-sex matched controls were extracted for white matter regions based on John Hopkin's Mori white matter atlas and partially correlated against professional training time and level of chess proficiency. Diffusion MRI connectometry was implemented to identify changes in structural connectivity in professional players compared to novices. Result: Compared to novices, higher planar anisotropy (CP) was observed in inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) and cingulate gyrus, in professional chess players, which correlated with higher RPM score in this group. Higher fractional anisotropy (FA) was observed in ILF, uncinate fasciculus (UF) and hippocampus and correlated with better scores in Raven's progressive matrices (RPM) score and longer duration of chess training in professional players. Consistently, radial diffusivity in bilateral IFOF, bilateral ILF and bilateral SLF was inversely correlated with level of training in professional players. DMRI connectometry analysis identified increased connectivity in bilateral UF, bilateral IFOF, bilateral cingulum, and corpus callosum in chess player's compared to controls. Conclusion: Structural connectivity of major associational subcortical white matter fibers are increased in professional chess players. FA and CP of ILF, SLF and UF directly correlates with duration of professional training and RPM score, in professional chess players. PMID:29773973

Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

PubMed

Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

2015-12-03

Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. Copyright © 2015. Published by Elsevier Inc.

Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study.

PubMed

Inder, Terrie E; Wells, Scott J; Mogridge, Nina B; Spencer, Carole; Volpe, Joseph J

2003-08-01

The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Women's Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse white matter atrophy, ventriculomegaly, immature gyral development, and enlarged subarachnoid space was found in 10 of 11 infants with birth gestation <26 weeks. Given the later outcome of these infants, this pattern may have very high risk for later global neurodevelopmental disability. This MRI study confirms a high incidence of cerebral white matter abnormality at term in an unselected population of premature infants, which is predominantly a result of noncystic injury in the extremely immature infant. We confirm that the major perinatal risk factors for white matter abnormality are related to perinatal infection, particularly maternal fever and infant sepsis, and hypotension with inotrope use. We have defined a distinct pattern of diffuse white and gray matter abnormality in the extremely immature infant.

Evidence for Functional Networks within the Human Brain's White Matter.

PubMed

Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

2017-07-05

Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry. SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders. Copyright © 2017 the authors 0270-6474/17/376394-14$15.00/0.

Early life predictors of brain development at term-equivalent age in infants born across the gestational age spectrum.

PubMed

Thompson, Deanne K; Kelly, Claire E; Chen, Jian; Beare, Richard; Alexander, Bonnie; Seal, Marc L; Lee, Katherine; Matthews, Lillian G; Anderson, Peter J; Doyle, Lex W; Spittle, Alicia J; Cheong, Jeanie L Y

2018-04-13

It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32-33 weeks' GA) and late (LP; 34-36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38-44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT). Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing. Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values. Early life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum. Copyright © 2018. Published by Elsevier Inc.

Extensive piano practicing has regionally specific effects on white matter development.

PubMed

Bengtsson, Sara L; Nagy, Zoltán; Skare, Stefan; Forsman, Lea; Forssberg, Hans; Ullén, Fredrik

2005-09-01

Using diffusion tensor imaging, we investigated effects of piano practicing in childhood, adolescence and adulthood on white matter, and found positive correlations between practicing and fiber tract organization in different regions for each age period. For childhood, practicing correlations were extensive and included the pyramidal tract, which was more structured in pianists than in non-musicians. Long-term training within critical developmental periods may thus induce regionally specific plasticity in myelinating tracts.

Brain white matter microstructure is associated with susceptibility to motion-induced nausea.

PubMed

Napadow, V; Sheehan, J; Kim, J; Dassatti, A; Thurler, A H; Surjanhata, B; Vangel, M; Makris, N; Schaechter, J D; Kuo, B

2013-05-01

Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion-induced nausea are due to microstructural differences in the inferior fronto-occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between-group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P < 0.001) higher nausea intensity to visual motion stimuli and had significantly (P < 0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea-processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes. © 2013 Blackwell Publishing Ltd.

Director Field Analysis (DFA): Exploring Local White Matter Geometric Structure in Diffusion MRI.

PubMed

Cheng, Jian; Basser, Peter J

2018-01-01

In Diffusion Tensor Imaging (DTI) or High Angular Resolution Diffusion Imaging (HARDI), a tensor field or a spherical function field (e.g., an orientation distribution function field), can be estimated from measured diffusion weighted images. In this paper, inspired by the microscopic theoretical treatment of phases in liquid crystals, we introduce a novel mathematical framework, called Director Field Analysis (DFA), to study local geometric structural information of white matter based on the reconstructed tensor field or spherical function field: (1) We propose a set of mathematical tools to process general director data, which consists of dyadic tensors that have orientations but no direction. (2) We propose Orientational Order (OO) and Orientational Dispersion (OD) indices to describe the degree of alignment and dispersion of a spherical function in a single voxel or in a region, respectively; (3) We also show how to construct a local orthogonal coordinate frame in each voxel exhibiting anisotropic diffusion; (4) Finally, we define three indices to describe three types of orientational distortion (splay, bend, and twist) in a local spatial neighborhood, and a total distortion index to describe distortions of all three types. To our knowledge, this is the first work to quantitatively describe orientational distortion (splay, bend, and twist) in general spherical function fields from DTI or HARDI data. The proposed DFA and its related mathematical tools can be used to process not only diffusion MRI data but also general director field data, and the proposed scalar indices are useful for detecting local geometric changes of white matter for voxel-based or tract-based analysis in both DTI and HARDI acquisitions. The related codes and a tutorial for DFA will be released in DMRITool. Copyright © 2017 Elsevier B.V. All rights reserved.

Edge Density Imaging: Mapping the Anatomic Embedding of the Structural Connectome Within the White Matter of the Human Brain

PubMed Central

Owen, Julia P.; Chang, Yi-Shin; Mukherjee, Pratik

2015-01-01

The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge betweenness centrality, we identify specific white matter regions involved in a large number of shortest paths, some containing highly connected rich club edges while others are relatively isolated within individual modules. Overall, these findings reveal an intricate relationship between white matter anatomy and the structural connectome, motivating further exploration of EDI for biomarkers of cognition and behavior. PMID:25592996

Presence of lacunar infarctions is associated with the spatial navigation impairment in patients with mild cognitive impairment: a DTI study

PubMed Central

Liu, Qing-Ping; He, Wen-Wen; Ding, Hong; Nedelska, Zuzana; Hort, Jakub; Zhang, Bing; Xu, Yun

2016-01-01

Lacunar cerebral infarction (LI) is one of risk factors of vascular dementia and correlates with progression of cognitive impairment including the executive functions. However, little is known on spatial navigation impairment and its underlying microstructural alteration of white matter in patients with LI and with or without mild cognitive impairment (MCI). Our aim was to investigate whether the spatial navigation impairment correlated with the white matter integrity in LI patients with MCI (LI-MCI). Thirty patients with LI were included in the study and were divided into LI-MCI (n=17) and non MCI (LI-Non MCI) groups (n=13) according neuropsychological tests.The microstructural integrity of white matter was assessed by calculating a fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) scans. The spatial navigation accuracy, separately evaluated as egocentric and allocentric, was assessed by a computerized human analogue of the Morris Water Maze tests Amunet. LI-MCI performed worse than the CN and LI-NonMCI groups on egocentric and delayed spatial navigation subtests. LI-MCI patients have spatial navigation deficits. The microstructural abnormalities in diffuse brain regions, including hippocampus, uncinate fasciculus and other brain regions may contribute to the spatial navigation impairment in LI-MCI patients at follow-up. PMID:27861154

A diffusion tensor imaging study of suicide attempters

PubMed Central

Thapa-Chhetry, Binod; Sublette, M. Elizabeth; Sullivan, Gregory M.; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

2014-01-01

Background Few studies have examined white matter abnormalities in suicide attempters using diffusion tensor imaging (DTI). This study sought to identify white matter regions altered in individuals with a prior suicide attempt. Methods DTI scans were acquired in 13 suicide attempters with major depressive disorder (MDD), 39 non-attempters with MDD, and 46 healthy participants (HP). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) was determined in the brain using two methods: region of interest (ROI) and tract-based spatial statistics (TBSS). ROIs were limited a priori to white matter adjacent to the caudal anterior cingulate cortex, rostral anterior cingulate cortex, dorsomedial prefrontal cortex, and medial orbitofrontal cortex. Results Using the ROI approach, suicide attempters had lower FA than MDD non-attempters and HP in the dorsomedial prefrontal cortex. Uncorrected TBSS results confirmed a significant cluster within the right dorsomedial prefrontal cortex indicating lower FA in suicide attempters compared to non-attempters. There were no differences in ADC when comparing suicide attempters, non-attempters and HP groups using ROI or TBSS methods. Conclusions Low FA in the dorsomedial prefrontal cortex was associated with a suicide attempt history. Converging findings from other imaging modalities support this finding, making this region of potential interest in determining the diathesis for suicidal behavior. PMID:24462041

Sex differences in adolescent white matter architecture.

PubMed

Bava, Sunita; Boucquey, Veronique; Goldenberg, Diane; Thayer, Rachel E; Ward, Megan; Jacobus, Joanna; Tapert, Susan F

2011-02-23

Sex-specific trajectories in white matter development during adolescence may help explain cognitive and behavioral divergences between males and females. Knowledge of sex differences in typically developing adolescents can provide a basis for interpreting sexual dimorphisms in abilities and actions. We examined 58 healthy adolescents (12-14years of age) with diffusion tensor imaging (DTI). Diffusion parameters fractional anisotropy (FA), and mean (MD), radial (RD), and axial diffusivities (AD) were subjected to whole-brain voxel-wise group comparisons using tract-based spatial statistics. Sex differences in white matter microstructure were examined in relation to pubertal development. Early adolescent females (n=29) evidenced higher FA in the right superior corona radiata, higher FA and AD in bilateral corticospinal tracts (≥164μl, p<.01), and lower MD in the right inferior longitudinal fasciculus (ILF) and left forceps major (≥164μl, p<.01) than age-matched males (n=29). Males did not show any areas of higher FA or lower MD than females, but had higher AD in the right superior longitudinal fasciculus, ILF, and forceps minor (≥ 164μl, p<.01). Pubertal stage did not account for sex disparities. In early adolescence, females' motor tracts may reflect widespread changes, while males may undergo relatively more microstructural change in projection and association fibers. Copyright © 2010 Elsevier B.V. All rights reserved.

Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging.

PubMed

Chaker, Layal; Cremers, Lotte G M; Korevaar, Tim I M; de Groot, Marius; Dehghan, Abbas; Franco, Oscar H; Niessen, Wiro J; Ikram, M Arfan; Peeters, Robin P; Vernooij, Meike W

2018-01-01

Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (β = 6.73 mL, 95% confidence interval = 2.94-9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

On Facilitating the use of HARDI in population studies by creating Rotation-Invariant Markers

PubMed Central

Caruyer, Emmanuel; Verma, Ragini

2014-01-01

We design and evaluate a novel method to compute rotationally invariant features using High Angular Resolution Diffusion Imaging (HARDI) data. These measures quantify the complexity of the angular diffusion profile modeled using a higher order model, thereby giving more information than classical diffusion tensor-derived parameters. The method is based on the spherical harmonic (SH) representation of the angular diffusion information, and is generalizable to a range of HARDI reconstruction models. These scalars are obtained as homogeneous polynomials of the SH representation of a HARDI reconstruction model. We show that finding such polynomials is equivalent to solving a large linear system of equations, and present a numerical method based on sparse matrices to efficiently solve this system. Among the solutions, we only keep a subset of algebraically independent polynomials, using an algorithm based on a numerical implementation of the Jacobian criterion. We compute a set of 12 or 25 rotationally invariant measures representative of the underlying white matter for the rank-4 or rank-6 spherical harmonics (SH) representation of the apparent diffusion coefficient (ADC) profile, respectively. Synthetic data was used to investigate and quantify the difference in contrast. Real data acquired with multiple repetitions showed that within subject variation in the invariants was less than the difference across subjects - facilitating their use to study population differences. These results demonstrate that our measures are able to characterize white matter, especially complex white matter found in regions of fiber crossings and hence can be used to derive new biomarkers for HARDI and can be used for HARDI-based population analysis. PMID:25465846

Twin-singleton developmental study of brain white matter anatomy.

PubMed

Sadeghi, Neda; Gilmore, John H; Gerig, Guido

2017-02-01

Twin studies provide valuable insights into the analysis of genetic and environmental factors influencing human brain development. However, these findings may not generalize to singletons due to differences in pre- and postnatal environments. One would expect the effect of these differences to be greater during the early years of life. To address this concern, we compare longitudinal diffusion data of white matter regions for 26 singletons and 76 twins (monozygotic and dizygotic) from birth to 2 years of age. We use nonlinear mixed effect modeling where the temporal changes in the diffusion parameters are described by the Gompertz function. The Gompertz function describes growth trajectory in terms of intuitive parameters: asymptote, delay, and speed. We analyzed fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) for 21 regions of interest (ROIs). These ROIs included areas in the association, projection, and commissural fiber tracts. We did not find any differences in the diffusion parameters between monozygotic and dizygotic twins. In addition, FA and RD showed no developmental differences between singletons and twins for the regions analyzed. However, the delay parameter of the Gompertz function of AD for the anterior limb of the internal capsule and anterior corona radiata was significantly different between singletons and twins. Further analysis indicated that the differences are small, and twins "catch up" by the first few months of life. These results suggest that the effects of differences of pre- and postnatal environments between twins and singletons are minimal on white matter development and disappear early in life. Hum Brain Mapp 38:1009-1024, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

PubMed Central

Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

2015-01-01

Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

Optimization of white matter tractography for pre-surgical planning and image-guided surgery.

PubMed

Arfanakis, Konstantinos; Gui, Minzhi; Lazar, Mariana

2006-01-01

Accurate localization of white matter fiber tracts in relation to brain tumors is a goal of critical importance to the neurosurgical community. White matter fiber tractography by means of diffusion tensor magnetic resonance imaging (DTI) is the only non-invasive method that can provide estimates of brain connectivity. However, conventional tractography methods are based on data acquisition techniques that suffer from image distortions and artifacts. Thus, a large percentage of white matter fiber bundles are distorted, and/or terminated early, while others are completely undetected. This severely limits the potential of fiber tractography in pre-surgical planning and image-guided surgery. In contrast, Turboprop-DTI is a technique that provides images with significantly fewer distortions and artifacts than conventional DTI data acquisition methods. The purpose of this study was to evaluate fiber tracking results obtained from Turboprop-DTI data. It was demonstrated that Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers than conventional DTI methods, especially in applications such as pre-surgical planning and image-guided surgery.

Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

PubMed

Hubbard, Nicholas A; Turner, Monroe; Hutchison, Joanna L; Ouyang, Austin; Strain, Jeremy; Oasay, Larry; Sundaram, Saranya; Davis, Scott; Remington, Gina; Brigante, Ryan; Huang, Hao; Hart, John; Frohman, Teresa; Frohman, Elliot; Biswal, Bharat B; Rypma, Bart

2016-11-01

Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences. © The Author(s) 2015.

The role of tissue microstructure and water exchange in biophysical modelling of diffusion in white matter.

PubMed

Nilsson, Markus; van Westen, Danielle; Ståhlberg, Freddy; Sundgren, Pia C; Lätt, Jimmy

2013-08-01

Biophysical models that describe the outcome of white matter diffusion MRI experiments have various degrees of complexity. While the simplest models assume equal-sized and parallel axons, more elaborate ones may include distributions of axon diameters and axonal orientation dispersions. These microstructural features can be inferred from diffusion-weighted signal attenuation curves by solving an inverse problem, validated in several Monte Carlo simulation studies. Model development has been paralleled by microscopy studies of the microstructure of excised and fixed nerves, confirming that axon diameter estimates from diffusion measurements agree with those from microscopy. However, results obtained in vivo are less conclusive. For example, the amount of slowly diffusing water is lower than expected, and the diffusion-encoded signal is apparently insensitive to diffusion time variations, contrary to what may be expected. Recent understandings of the resolution limit in diffusion MRI, the rate of water exchange, and the presence of microscopic axonal undulation and axonal orientation dispersions may, however, explain such apparent contradictions. Knowledge of the effects of biophysical mechanisms on water diffusion in tissue can be used to predict the outcome of diffusion tensor imaging (DTI) and of diffusion kurtosis imaging (DKI) studies. Alterations of DTI or DKI parameters found in studies of pathologies such as ischemic stroke can thus be compared with those predicted by modelling. Observations in agreement with the predictions strengthen the credibility of biophysical models; those in disagreement could provide clues of how to improve them. DKI is particularly suited for this purpose; it is performed using higher b-values than DTI, and thus carries more information about the tissue microstructure. The purpose of this review is to provide an update on the current understanding of how various properties of the tissue microstructure and the rate of water exchange between microenvironments are reflected in diffusion MRI measurements. We focus on the use of biophysical models for extracting tissue-specific parameters from data obtained with single PGSE sequences on clinical MRI scanners, but results obtained with animal MRI scanners are also considered. While modelling of white matter is the central theme, experiments on model systems that highlight important aspects of the biophysical models are also reviewed.

A New Approach for Deep Gray Matter Analysis Using Partial-Volume Estimation.

PubMed

Bonnier, Guillaume; Kober, Tobias; Schluep, Myriam; Du Pasquier, Renaud; Krueger, Gunnar; Meuli, Reto; Granziera, Cristina; Roche, Alexis

2016-01-01

The existence of partial volume effects in brain MR images makes it challenging to understand physio-pathological alterations underlying signal changes due to pathology across groups of healthy subjects and patients. In this study, we implement a new approach to disentangle gray and white matter alterations in the thalamus and the basal ganglia. The proposed method was applied to a cohort of early multiple sclerosis (MS) patients and healthy subjects to evaluate tissue-specific alterations related to diffuse inflammatory or neurodegenerative processes. Forty-three relapsing-remitting MS patients and nineteen healthy controls underwent 3T MRI including: (i) fluid-attenuated inversion recovery, double inversion recovery, magnetization-prepared gradient echo for lesion count, and (ii) T1 relaxometry. We applied a partial volume estimation algorithm to T1 relaxometry maps to gray and white matter local concentrations as well as T1 values characteristic of gray and white matter in the thalamus and the basal ganglia. Statistical tests were performed to compare groups in terms of both global T1 values, tissue characteristic T1 values, and tissue concentrations. Significant increases in global T1 values were observed in the thalamus (p = 0.038) and the putamen (p = 0.026) in RRMS patients compared to HC. In the Thalamus, the T1 increase was associated with a significant increase in gray matter characteristic T1 (p = 0.0016) with no significant effect in white matter. The presented methodology provides additional information to standard MR signal averaging approaches that holds promise to identify the presence and nature of diffuse pathology in neuro-inflammatory and neurodegenerative diseases.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs.

PubMed

Klauser, Paul; Baker, Simon T; Cropley, Vanessa L; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T; Loughland, Carmel; Catts, Stanley V; Mowry, Bryan; Weickert, Thomas W; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

2017-03-01

White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy.

PubMed

Keller, Simon S; Glenn, G Russell; Weber, Bernd; Kreilkamp, Barbara A K; Jensen, Jens H; Helpern, Joseph A; Wagner, Jan; Barker, Gareth J; Richardson, Mark P; Bonilha, Leonardo

2017-01-01

Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe. However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle. Using receiver operating characteristic curves, diffusion characteristics of these regions could classify individual patients according to outcome with 84% sensitivity and 89% specificity. Pathological changes in the dorsal fornix were beyond the margins of resection, and contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Furthermore, diffusion characteristics of the ipsilateral uncinate could classify patients from controls with a sensitivity of 98%; importantly, by co-registering the preoperative fibre maps to postoperative surgical lacuna maps, we observed that the extent of uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network. These results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

PubMed Central

Keller, Simon S; Glenn, G Russell; Weber, Bernd; Kreilkamp, Barbara A K; Jensen, Jens H; Helpern, Joseph A; Wagner, Jan; Barker, Gareth J; Richardson, Mark P; Bonilha, Leonardo

2017-01-01

Abstract Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe. However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle. Using receiver operating characteristic curves, diffusion characteristics of these regions could classify individual patients according to outcome with 84% sensitivity and 89% specificity. Pathological changes in the dorsal fornix were beyond the margins of resection, and contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Furthermore, diffusion characteristics of the ipsilateral uncinate could classify patients from controls with a sensitivity of 98%; importantly, by co-registering the preoperative fibre maps to postoperative surgical lacuna maps, we observed that the extent of uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network. These results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures. PMID:28031219

Vascular Dysfunction in Leukoaraiosis.

PubMed

Sam, K; Crawley, A P; Poublanc, J; Conklin, J; Sobczyk, O; Mandell, D M; Duffin, J; Venkatraghavan, L; Fisher, J A; Black, S E; Mikulis, D J

2016-12-01

The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis. © 2016 by American Journal of Neuroradiology.

Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

PubMed

Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

2011-08-01

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors.

PubMed

Dean, Justin M; Riddle, Art; Maire, Jennifer; Hansen, Kelly D; Preston, Marnie; Barnes, Anthony P; Sherman, Larry S; Back, Stephen A

2011-07-05

CNS myelination disturbances commonly occur in chronic white matter lesions in neurodevelopmental and adult neurological disorders. Recent studies support that myelination failure can involve a disrupted cellular repair mechanism where oligodendrocyte (OL) progenitor cells (OPCs) proliferate in lesions with diffuse astrogliosis, but fail to fully differentiate to mature myelinating OLs. There are no in vitro models that reproduce these features of myelination failure. Forebrain coronal slices from postnatal day (P) 0.5/1 rat pups were cultured for 1, 5, or 9 days in vitro (DIV). Slices rapidly exhibited diffuse astrogliosis and accumulation of the extracellular matrix glycosaminoglycan hyaluronan (HA), an inhibitor of OPC differentiation and re-myelination. At 1 DIV ~1.5% of Olig2+ OLs displayed caspase-3 activation, which increased to ~11.5% by 9 DIV. At 1 DIV the density of PDGFRα+ and PDGFRα+/Ki67+ OPCs were significantly elevated compared to 0 DIV (P < 0.01). Despite this proliferative response, at 9 DIV ~60% of white matter OLs were late progenitors (preOLs), compared to ~7% in the postnatal day 10 rat (P < 0.0001), consistent with preOL maturation arrest. Addition of HA to slices significantly decreased the density of MBP+ OLs at 9 DIV compared to controls (217 ± 16 vs. 328 ± 17 cells/mm2, respectively; P = 0.0003), supporting an inhibitory role of HA in OL lineage progression in chronic lesions. Diffuse white matter astrogliosis and early OPC proliferation with impaired OL maturation were reproduced in this model of myelination failure. This system may be used to define mechanisms of OPC maturation arrest and myelination failure related to astrogliosis and HA accumulation.

Imaging White Matter in Human Brainstem

PubMed Central

Ford, Anastasia A.; Colon-Perez, Luis; Triplett, William T.; Gullett, Joseph M.; Mareci, Thomas H.; FitzGerald, David B.

2013-01-01

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo. PMID:23898254

Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications.

PubMed

Newcombe, Virginia F J; Williams, Guy B; Scoffings, Daniel; Cross, Justin; Carpenter, T Adrian; Pickard, John D; Menon, David K

2010-05-01

An improved in vivo understanding of variations in neuropathology in the vegetative state (VS) may aid diagnosis, improve prognostication and help refine the selection of patients for particular treatment regimes. The authors have used diffusion tensor imaging (DTI) to characterise the extent and location of white matter loss in VS secondary to traumatic brain injury (TBI) and ischaemic-hypoxic injury. Twelve patients with VS (seven TBI, five ischaemic/hypoxic injuries) underwent MRI including DTI at a minimum of 3 months postinjury. Mean apparent diffusion coefficient, fractional anisotropy and eigenvalues were obtained for whole-brain grey and white matter, the pons, thalamus, ventral midbrain, dorsal midbrain and the corpus callosum. DTI measures of supratentorial damage were compared with a summed measure from the JFK modified Coma Recovery Scale (CRS-R) and with a three-point scale of functional magnetic resonance imaging (fMRI) response to an auditory paradigm to assess whether residual integrity of supratentorial white matter connectivity correlated with cortical processing. Conventional radiological approaches did not detect lesions in regions where quantitative DTI demonstrated abnormalities. There was evidence of marked, broadly similar, abnormalities in the supratentorial grey- and white-matter compartments from both aetiologies. In contrast, discordant findings were found in the infratentorial compartment, with DTI abnormalities in the brainstem confined to the TBI group. Supratentorial DTI abnormalities correlated with the CRS-R as well as responses to an fMRI paradigm that detected convert cognitive processing. DTI may help to characterise differences in patients in VS. These findings may have implications for response to therapies, and should be taken into account in trials of interventions aimed at arousal in VS.

Imaging white matter in human brainstem.

PubMed

Ford, Anastasia A; Colon-Perez, Luis; Triplett, William T; Gullett, Joseph M; Mareci, Thomas H; Fitzgerald, David B

2013-01-01

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.

White matter integrity in polydrug users in relation to attachment and personality: a controlled diffusion tensor imaging study.

PubMed

Unterrainer, H F; Hiebler, M; Ragger, K; Froehlich, L; Koschutnig, K; Schoeggl, H; Kapfhammer, H P; Papousek, I; Weiss, E M; Fink, A

2016-12-01

The relationship between substance use disorders (SUD) and brain deficits has been studied extensively. However, there is still a lack of research focusing on the structural neural connectivity in long-term polydrug use disorder (PUD). Since a deficiency in white matter integrity has been reported as being related to various parameters of increased psychopathology, it might be considered an aggravating factor in the treatment of SUD. In this study we compared two groups of PUD inpatients (abstinent: n = 18, in maintenance treatment: n = 15) to healthy controls (n = 16) with respect to neural connectivity in white matter, and their relation to behavioral parameters of personality factors/organization and attachment styles. Diffusion Tensor Imaging was used to investigate white matter structure. Compared with healthy controls, the PUD patients showed reduced fractional anisotropy (FA) and increased radial diffusivity (RD) mainly in the superior fasciculus longitudinalis and the superior corona radiata. These findings suggest diminished neural connectivity as a result of myelin pathology in PUD patients. In line with our assumptions, we observed FA in the biggest cluster as negatively correlated with anxious attachment (r = 0.36, p < 0.05), personality dysfunctioning (r = -0.41; p < 0.01) as well positively correlated with personality factors Openness (r = 0.34; p < 0.05) and Agreeableness (r = 0.28; p < 0.05). Correspondingly these findings were inversely mirrored by RD. Further research employing enhanced samples and addressing longitudinally neuronal plastic effects of SUD treatment in relation to changes in personality and attachment is recommended.

Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder.

PubMed

Schweren, L J S; Hartman, C A; Zwiers, M P; Heslenfeld, D J; Franke, B; Oosterlaan, J; Buitelaar, J K; Hoekstra, P J

2016-04-01

Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity within the frontal-striatal and mesolimbic pathways, in a large sample of children, adolescents and young adults with ADHD. Participants with ADHD (N=172; mean age 17, range 9-26) underwent diffusion-weighted MRI scanning, along with an age- and gendermatched group of 96 control participants. Five study-specific white matter tract masks (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medialprefrontal-striatal) were created. First we analyzed case-control differences in fractional anisotropy (FA) and mean diffusivity (MD) within each tract. Second, FA and MD in each tract was predicted from cumulative stimulant intake within the ADHD group. After correction for multiple testing, participants with ADHD showed reduced FA in the orbitofrontal-striatal pathway (p=0.010, effect size=0.269). Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway (p=0.011, effect size=-0.164), but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. It fell short of significance after adding ADHD severity or ADHD type to the model (p=0.036 and p=0.094, respectively), while the effect size changed little. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD. Longitudinal studies including a drug-naïve baseline assessment are needed to distinguish between-subject variability in ADHD severity from treatment effects. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event.

PubMed

Li, Lei; Lei, Du; Li, Lingjiang; Huang, Xiaoqi; Suo, Xueling; Xiao, Fenglai; Kuang, Weihong; Li, Jin; Bi, Feng; Lui, Su; Kemp, Graham J; Sweeney, John A; Gong, Qiyong

2016-02-01

Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.

Exploring the neural substrates of attentional control and human intelligence: Diffusion tensor imaging of prefrontal white matter tractography in healthy cognition.

PubMed

Ohtani, Toshiyuki; Nestor, Paul G; Bouix, Sylvain; Newell, Dominick; Melonakos, Eric D; McCarley, Robert W; Shenton, Martha E; Kubicki, Marek

2017-01-26

We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition. Copyright © 2016. Published by Elsevier Ltd.

Relationship between white matter integrity and serum cortisol levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics.

PubMed

Liu, Xiaodan; Watanabe, Keita; Kakeda, Shingo; Yoshimura, Reiji; Abe, Osamu; Ide, Satoru; Hayashi, Kenji; Katsuki, Asuka; Umene-Nakano, Wakako; Watanabe, Rieko; Ueda, Issei; Nakamura, Jun; Korogi, Yukunori

2016-06-01

Higher daytime cortisol levels because of a hyperactive hypothalamic-pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts. To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method. The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement. Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected). Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal-subcortical and frontal-limbic circuits. © The Royal College of Psychiatrists 2016.

Alterations of white matter integrity in adults with major depressive disorder: a magnetic resonance imaging study

PubMed Central

Zou, Ke; Huang, Xiaoqi; Li, Tao; Gong, Qiyong; Li, Zhe; Ou-yang, Luo; Deng, Wei; Chen, Qin; Li, Chunxiao; Ding, Yi; Sun, Xueli

2008-01-01

Objective The purpose of our study was to investigate alterations of white matter integrity in adults with major depressive disorder (MDD) using magnetic resonance imaging (MRI). Methods We performed diffusion tensor imaging with a 3T MRI scanner on 45 patients with major depression and 45 healthy controls matched for age, sex and education. Using a voxel-based analysis, we measured the fractional anisotropy (FA), and we investigated the differences between the patient and control groups. We examined the correlations between the microstructure abnormalities of white matter and symptom severity, age of illness onset and cumulative illness duration, respectively. Results We found a significant decrease in FA in the left hemisphere, including the anterior limb of the internal capsule and the inferior parietal portion of the superior longitudinal fasciculus, in patients with MDD compared with healthy controls. Diffusion tensor imaging measures in the left anterior limb of the internal capsule were negatively related to the severity of depressive symptoms, even after we controlled for age and sex. Conclusion Our findings provide new evidence of microstructural changes of white matter in non–late-onset adult depression. Our results complement those observed in late-life depression and support the hypothesis that the disruption of cortical– subcortical circuit integrity may be involved in the etiology of major depressive disorder. PMID:18982175

Susceptibility Tensor Imaging (STI) of the Brain

PubMed Central

Li, Wei; Liu, Chunlei; Duong, Timothy Q.; van Zijl, Peter C.M.; Li, Xu

2016-01-01

Susceptibility tensor imaging (STI) is a recently developed MRI technique that allows quantitative determination of orientation-independent magnetic susceptibility parameters from the dependence of gradient echo signal phase on the orientation of biological tissues with respect to the main magnetic field. By modeling the magnetic susceptibility of each voxel as a symmetric rank-2 tensor, individual magnetic susceptibility tensor elements as well as the mean magnetic susceptibility (MMS) and magnetic susceptibility anisotropy (MSA) can be determined for brain tissues that would still show orientation dependence after conventional scalar-based quantitative susceptibility mapping (QSM) to remove such dependence. Similar to diffusion tensor imaging (DTI), STI allows mapping of brain white matter fiber orientations and reconstruction of 3D white matter pathways using the principal eigenvectors of the susceptibility tensor. In contrast to diffusion anisotropy, the main determinant factor of susceptibility anisotropy in brain white matter is myelin. Another unique feature of susceptibility anisotropy of white matter is its sensitivity to gadolinium-based contrast agents. Mechanistically, MRI-observed susceptibility anisotropy is mainly attributed to the highly ordered lipid molecules in myelin sheath. STI provides a consistent interpretation of the dependence of phase and susceptibility on orientation at multiple scales. This article reviews the key experimental findings and physical theories that led to the development of STI, its practical implementations, and its applications for brain research. PMID:27120169

White matter microstructure in boys with persistent depressive disorder.

PubMed

Vilgis, Veronika; Vance, Alasdair; Cunnington, Ross; Silk, Timothy J

2017-10-15

Persistent depressive symptoms in children and adolescents are considered a risk factor for the development of major depressive disorder (MDD) later in life. Previous research has shown alterations in white matter microstructure in pediatric MDD but discrepancies exist as to the specific tracts affected. The current study aimed to improve upon previous methodology and address the question whether previous findings of lower fractional anisotropy (FA) replicate in a sample of children with persistent depressive disorder characterized by mild but more chronic symptoms of depression. White matter microstructure was examined in 25 boys with persistent depressive disorder and 25 typically developing children. Tract specific analysis implemented with the Diffusion Tensor Imaging - ToolKit (DTI-TK) was used to probe fractional anisotropy (FA) in eleven major white matter tracts. Clusters within the left uncinate, inferior fronto-occipital and cerebrospinal tracts showed lower FA in the clinical group. FA in the left uncinate showed a negative association with self-reported symptoms of depression. The results demonstrate lower FA in several white matter tracts in children with persistent depressive disorder. These findings support the contention that early onset depression is associated with altered white matter microstructure, which may contribute to the maintenance and recurrence of symptoms. Copyright © 2017. Published by Elsevier B.V.

White Matter Integrity Deficit Associated with Betel Quid Dependence.

PubMed

Yuan, Fulai; Zhu, Xueling; Kong, Lingyu; Shen, Huaizhen; Liao, Weihua; Jiang, Canhua

2017-01-01

Betel quid (BQ) is a commonly consumed psychoactive substance, which has been regarded as a human carcinogen. Long-term BQ chewing may cause Diagnostic and Statistical Manual of Mental Disorders-IV dependence symptoms, which can lead to decreased cognitive functions, such as attention and inhibition control. Although betel quid dependence (BQD) individuals have been reported with altered brain structure and function, there is little evidence showing white matter microstructure alternation in BQD individuals. The present study aimed to investigate altered white matter microstructure in BQD individuals using diffusion tensor imaging. Tract-based spatial statistics was used to analyze the data. Compared with healthy controls, BQD individuals exhibited higher mean diffusivity (MD) in anterior thalamic radiation (ATR). Further analysis revealed that the ATR in BQD individuals showed less fractional anisotropy (FA) than that in healthy controls. Correlation analysis showed that both the increase of MD and reduction of FA in BQD individuals were associated with severity of BQ dependence. These results suggested that BQD would disrupt the balance between prefrontal cortex and subcortical areas, causing declined inhibition control.

Traumatic brain injury impairs small-world topology

PubMed Central

Pandit, Anand S.; Expert, Paul; Lambiotte, Renaud; Bonnelle, Valerie; Leech, Robert; Turkheimer, Federico E.

2013-01-01

Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a “small-world” organization following traumatic brain injury (TBI). Methods: We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging. Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions: We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. PMID:23596068

Diffusion-weighted MRI measures suggest increased white-matter integrity in Internet gaming disorder: Evidence from the comparison with recreational Internet game users.

PubMed

Dong, Guangheng; Wu, Lingdan; Wang, Ziliang; Wang, Yifan; Du, Xiaoxia; Potenza, Marc N

2018-06-01

Several studies have suggested that Internet gaming disorder (IGD) is related to altered brain white matter integrity. However, seeming inconsistencies exist and may reflect comparison groups not matched well for certain gaming characteristics. In order to address this possible concern, we recruited in the present study individuals with recreational Internet game use (RGU) comprised of individuals who spend similar amounts of time as IGD subjects playing online games without developing IGD. Diffusion tensor imaging data were collected from 42 IGD and 44 RGU subjects. Whole-brain comparisons showed that IGD subjects demonstrated increased fractional anisotropy (FA) in the bilateral anterior thalamic radiation, anterior limb of the internal capsule, bilateral corticospinal tract, bilateral inferior fronto-occipital fasciculus, corpus callosum, and bilateral inferior longitudinal fasciculus. In addition, Internet-addiction severity was positively correlated with FA values. Taken together, we conclude that IGD is associated with measures of increased white-matter integrity in tracts linking reward circuitry and sensory and motor control systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

White matter lesions relate to tract-specific reductions in functional connectivity.

PubMed

Langen, Carolyn D; Zonneveld, Hazel I; White, Tonya; Huizinga, Wyke; Cremers, Lotte G M; de Groot, Marius; Ikram, Mohammad Arfan; Niessen, Wiro J; Vernooij, Meike W

2017-03-01

White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections. Copyright © 2016 Elsevier Inc. All rights reserved.

Impaired empathic abilities and reduced white matter integrity in schizophrenia.

PubMed

Fujino, Junya; Takahashi, Hidehiko; Miyata, Jun; Sugihara, Genichi; Kubota, Manabu; Sasamoto, Akihiko; Fujiwara, Hironobu; Aso, Toshihiko; Fukuyama, Hidenao; Murai, Toshiya

2014-01-03

Empathic abilities are impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, the relationship between empathic disabilities and altered white matter in the disorder remains unclear. The present study tested associations between empathic disabilities and white matter integrity in order to investigate the neural basis of impaired empathy in schizophrenia. Sixty-nine patients with schizophrenia and 69 age-, gender-, handedness-, education- and IQ level-matched healthy controls underwent diffusion-weighted imaging. Empathic abilities were assessed using the Interpersonal Reactivity Index (IRI). Using tract-based spatial statistics (TBSS), the associations between empathic abilities and white matter fractional anisotropy (FA), a measure of white matter integrity, were examined in the patient group within brain areas that showed a significant FA reduction compared with the controls. The patients with schizophrenia reported lower perspective taking and higher personal distress according to the IRI. The patients showed a significant FA reduction in bilateral deep white matter in the frontal, temporal, parietal and occipital lobes, a large portion of the corpus callosum, and the corona radiata. In schizophrenia patients, fantasy subscales positively correlated with FA in the left inferior fronto-occipital fasciculi and anterior thalamic radiation, and personal distress subscales negatively correlated with FA in the splenium of the corpus callosum. These results suggest that disrupted white matter integrity in these regions constitutes a pathology underpinning specific components of empathic disabilities in schizophrenia, highlighting that different aspects of empathic impairments in the disorder would have, at least partially, distinct neuropathological bases. © 2013.

Atypical Frontal-Striatal-Thalamic Circuit White Matter Development in Pediatric Obsessive Compulsive Disorder

PubMed Central

Fitzgerald, Kate D.; Liu, Yanni; Reamer, Elyse N.; Taylor, Stephan F.; Welsh, Robert C.

2015-01-01

Objective Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients. Method To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. Results Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. Conclusions Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth, but confirmation of these possibilities awaits longitudinal work. PMID:25440312

Plasticity of left perisylvian white-matter tracts is associated with individual differences in math learning.

PubMed

Jolles, Dietsje; Wassermann, Demian; Chokhani, Ritika; Richardson, Jennifer; Tenison, Caitlin; Bammer, Roland; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2016-04-01

Plasticity of white matter tracts is thought to be essential for cognitive development and academic skill acquisition in children. However, a dearth of high-quality diffusion tensor imaging (DTI) data measuring longitudinal changes with learning, as well as methodological difficulties in multi-time point tract identification have limited our ability to investigate plasticity of specific white matter tracts. Here, we examine learning-related changes of white matter tracts innervating inferior parietal, prefrontal and temporal regions following an intense 2-month math tutoring program. DTI data were acquired from 18 third grade children, both before and after tutoring. A novel fiber tracking algorithm based on a White Matter Query Language (WMQL) was used to identify three sections of the superior longitudinal fasciculus (SLF) linking frontal and parietal (SLF-FP), parietal and temporal (SLF-PT) and frontal and temporal (SLF-FT) cortices, from which we created child-specific probabilistic maps. The SLF-FP, SLF-FT, and SLF-PT tracts identified with the WMQL method were highly reliable across the two time points and showed close correspondence to tracts previously described in adults. Notably, individual differences in behavioral gains after 2 months of tutoring were specifically correlated with plasticity in the left SLF-FT tract. Our results extend previous findings of individual differences in white matter integrity, and provide important new insights into white matter plasticity related to math learning in childhood. More generally, our quantitative approach will be useful for future studies examining longitudinal changes in white matter integrity associated with cognitive skill development.

Glycogen accumulation in the central nervous system in the cerebro-hepato-renal syndrome. Report of a case with ultrastructural studies.

PubMed

Agamanolis, D P; Patre, S

1979-05-01

We found marked accumulation of glycogen in the brain in one case of the cerebro-hepato-renal syndrome (CHRS). Glycogen in the form of beta-particles was deposited freely within the nucleus, perikaryon and cell processes of neurons and glial cells. The changes involved the gray matter diffusely but were more prominent in the cerebral cortex. The patient died at the age of 4 months after a clinical course characterized by severe hypotonia, seizures, and apneic episodes. Other neuropathologic findings were developmental malformations of the central nervous systen (CNS) (pachygyria, polymicrogyria, and hypoplasia of the inferior olives), white matter abnormalities (deficiency in myelination and diffuse accumulation of sudanophilic droplets within glial cells), clusters of peculiar "globoid" histiocytes with pleomorphic lipid inclusions, and microglial nodules in gray and white matter. This unusual combination of findings is regarded as characteristic of the CHRS.

Imaging Effects of Neurotrophic Factor Genes on Brain Plasticity and Repair in Multiple Sclerosis

DTIC Science & Technology

2011-07-01

focal and diffuse effects in brain (including cortical thickness and subcortical volume measures, lesion volumetry , and voxel-based morphometry and...to both focal and diffuse effects in gray and white matter, including cortical thickness and subcortical volume measures, lesion volumetry , and

The relationship between white matter abnormalities and cognitive functions in new-onset juvenile myoclonic epilepsy.

PubMed

Ekmekci, Burcu; Bulut, Hacı Taner; Gümüştaş, Funda; Yıldırım, Adem; Kuştepe, Ali

2016-09-01

Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the corticothalamic pathway have been detected in adult patients with JME. It has been demonstrated that, in adult patients with JME, frontal dysfunction is related to subcortical white matter damage and decreased volume in frontal cortical gray matter and the thalamus. Many studies have focused on adult patients. Twenty-four patients and 28 controls were evaluated. The group with JME had significantly worse results for the word fluency, trail-B, and Stroop tests that assessed executive functions. A significant decrease in FA values in the dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the right thalamus, the posterior cingulate, the corpus callosum anterior, the corona radiata, and the middle frontal white matter (MFWM) and an increase in ADC values in patients with JME were detected. The correlation between FA values in DLPFC and the letter fluency test results was positive, and the correlation with the Stroop and trail-B test results was negative. We found a negative correlation between SMA, anterior thalamus, and MFWM FA values and the trail-B test results and a positive correlation between the SMA, anterior thalamus, and MFWM FA values and the letter fluency test results. We detected white matter and gray matter abnormalities in patients with new-onset JME using DTI. In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters. We evaluated newly diagnosed patients with JME in our study. That leads us to believe that microstructural abnormalities exist from the very beginning of the disease and that they result from the genetic basis of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

White matter correlates of sensory processing in autism spectrum disorders

PubMed Central

Pryweller, Jennifer R.; Schauder, Kimberly B.; Anderson, Adam W.; Heacock, Jessica L.; Foss-Feig, Jennifer H.; Newsom, Cassandra R.; Loring, Whitney A.; Cascio, Carissa J.

2014-01-01

Autism spectrum disorder (ASD) has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure. PMID:25379451

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults.

PubMed

Moore, Elizabeth E; Liu, Dandan; Pechman, Kimberly R; Terry, James G; Nair, Sangeeta; Cambronero, Francis E; Bell, Susan P; Gifford, Katherine A; Anderson, Adam W; Hohman, Timothy J; Carr, John Jeffrey; Jefferson, Angela L

2018-06-26

Left ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment. Vanderbilt Memory & Aging Project participants free of clinical stroke, dementia, and heart failure (n=318, 73±7 years, 58% male, 39% mild cognitive impairment) underwent brain magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological assessment. Voxelwise analyses related LV mass index (g/m 2 ) to diffusion tensor imaging metrics. Models adjusted for age, sex, education, race/ethnicity, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E-ε4 status. Secondary analyses included a LV mass index×diagnosis interaction term with follow-up models stratified by diagnosis. With identical covariates, linear regression models related LV mass index to neuropsychological performances. Increased LV mass index related to altered white matter microstructure ( P <0.05). In models stratified by diagnosis, associations between LV mass index and diffusion tensor imaging were present among mild cognitive impairment participants only ( P <0.05). LV mass index was related only to worse visuospatial memory performance (β=-0.003, P =0.036), an observation that would not withstand correction for multiple testing. In the absence of prevalent heart failure and clinical stroke, increased LV mass index corresponds to altered white matter microstructure, particularly among older adults with clinical symptoms of prodromal dementia. Findings highlight the potential link between subclinical LV remodeling and cerebral white matter microstructure vulnerability. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

PubMed

Fitzgerald, Jacqueline; Leemans, Alexander; Kehoe, Elizabeth; O'Hanlon, Erik; Gallagher, Louise; McGrath, Jane

2018-03-01

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Adult cerebral adrenoleukodystrophy and Addison's disease in a female carrier.

PubMed

Chen, Xiaoyan; Chen, Zhiye; Huang, Dehui; Liu, Xiaofeng; Gui, Qiuping; Yu, Shengyuan

2014-07-10

We described a 38-year-old woman of rapidly progressive dementia with white matter encephalopathy and death. She had Addison's disease but the adrenal glands were hyperplastic. Brain magnetic resonance imaging revealed diffuse white matter lesion predominantly in the frontal lobe with band-like contrast enhancement. l-Methyl-11C-methionine positron emission tomography revealed accumulation of tracer in bilateral frontal lobes. Stereotactic biopsy demonstrated demyelination changes. A number of urinary organic acids were elevated. Adrenoleukodystrophy was diagnosed by elevated plasma very long chain fatty acid and ABCD1 gene mutation (C1544C/T). Adrenoleukodystrophy should be considered as a differential diagnosis in women with rapidly progressive white matter encephalopathy. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness.

PubMed

Rayhan, Rakib U; Stevens, Benson W; Timbol, Christian R; Adewuyi, Oluwatoyin; Walitt, Brian; VanMeter, John W; Baraniuk, James N

2013-01-01

Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.

Minocycline protects the immature white matter against hyperoxia.

PubMed

Schmitz, Thomas; Krabbe, Grietje; Weikert, Georg; Scheuer, Till; Matheus, Friederike; Wang, Yan; Mueller, Susanne; Kettenmann, Helmut; Matyash, Vitali; Bührer, Christoph; Endesfelder, Stefanie

2014-04-01

Poor neurological outcome in preterm infants is associated with periventricular white matter damage and hypomyelination, often caused by perinatal inflammation, hypoxia-ischemia, and hyperoxia. Minocycline has been demonstrated in animal models to protect the immature brain against inflammation and hypoxia-ischemia by microglial inhibition. Here we studied the effect of minocycline on white matter damage caused by hyperoxia. To mimic the 3- to 4-fold increase of oxygen tension caused by preterm birth, we have used the hyperoxia model in neonatal rats providing 24h exposure to 4-fold increased oxygen concentration (80% instead of 21% O2) from P6 to P7. We analyzed whether minocycline prevents activation of microglia and damage of oligodendroglial precursor cell development, and whether acute treatment of hyperoxia-exposed rats with minocycline improves long term white matter integrity. Minocycline administration during exposure to hyperoxia resulted in decreased apoptotic cell death and in improved proliferation and maturation of oligodendroglial precursor cells (OPC). Minocycline blocked changes in microglial morphology and IL-1β release induced by hyperoxia. In primary microglial cell cultures, minocycline inhibited cytokine release while in mono-cultures of OPCs, it improved survival and proliferation. Long term impairment of white matter diffusivity in MRI/DTI in P30 and P60 animals after neonatal hyperoxia was attenuated by minocycline. Minocycline protects white matter development against oxygen toxicity through direct protection of oligodendroglia and by microglial inhibition. This study moreover demonstrates long term benefits of minocycline on white matter integrity. Copyright © 2014 Elsevier Inc. All rights reserved.

White Matter Integrity, Substance Use, and Risk Taking in Adolescence

PubMed Central

Jacobus, Joanna; Thayer, Rachel E.; Trim, Ryan S.; Bava, Sunita; Frank, Lawrence R.; Tapert, Susan F.

2012-01-01

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n=47) and demographically similar non-users (n=49) received diffusion tensor imaging at baseline (ages 16–19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17–20). Brain regions of interest were: fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance using youth (n=47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 =10–12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic system fibers and future substance use frequency. Subcortical white matter coherence along with an imbalance between the maturation levels in cognitive control and reward systems may disadvantage the resistance to engage in risk taking behaviors during adolescence. PMID:22564204

White matter integrity, substance use, and risk taking in adolescence.

PubMed

Jacobus, Joanna; Thayer, Rachel E; Trim, Ryan S; Bava, Sunita; Frank, Lawrence R; Tapert, Susan F

2013-06-01

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence. 2013 APA, all rights reserved

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

PubMed

Sheikh, Haroon I; Joanisse, Marc F; Mackrell, Sarah M; Kryski, Katie R; Smith, Heather J; Singh, Shiva M; Hayden, Elizabeth P

2014-01-01

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

Surface Based Analysis of Diffusion Orientation for Identifying Architectonic Domains in the In Vivo Human Cortex

PubMed Central

McNab, Jennifer A.; Polimeni, Jonathan R.; Wang, Ruopeng; Augustinack, Jean C.; Fujimoto, Kyoko; Player, Allison; Janssens, Thomas; Farivar, Reza; Folkerth, Rebecca D.; Vanduffel, Wim; Wald, Lawrence L.

2012-01-01

Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in grey matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical grey matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1. PMID:23247190

Imaging Effects of Neurotrophic Factor Genes on Brain Plasticity and Repair in Multiple Sclerosis

DTIC Science & Technology

2012-07-01

sensitive to focal and diffuse changes in brain tissue (including cortical thickness and subcortical volume measures, lesion volumetry , and voxel-based...sensitive to both focal and diffuse effects in gray and white matter, including cortical thickness and subcortical volume measures, lesion volumetry , and

Microstructural Integrity of the Corpus Callosum Linked with Neuropsychological Performance in Adolescents

ERIC Educational Resources Information Center

Fryer, Susanna L.; Frank, Lawrence R.; Spadoni, Andrea D.; Theilmann, Rebecca J.; Nagel, Bonnie J.; Schweinsburg, Alecia D.; Tapert, Susan F.

2008-01-01

Background: Diffusion tensor imaging (DTI) has revealed microstructural aspects of adolescent brain development, the cognitive correlates of which remain relatively uncharacterized. Methods: DTI was used to assess white matter microstructure in 18 typically developing adolescents (ages 16-18). Fractional anisotropy (FA) and mean diffusion (MD)…

Analysis of longitudinal diffusion-weighted images in healthy and pathological aging: An ADNI study.

PubMed

Kruggel, Frithjof; Masaki, Fumitaro; Solodkin, Ana

2017-02-15

The widely used framework of voxel-based morphometry for analyzing neuroimages is extended here to model longitudinal imaging data by exchanging the linear model with a linear mixed-effects model. The new approach is employed for analyzing a large longitudinal sample of 756 diffusion-weighted images acquired in 177 subjects of the Alzheimer's Disease Neuroimaging initiative (ADNI). While sample- and group-level results from both approaches are equivalent, the mixed-effect model yields information at the single subject level. Interestingly, the neurobiological relevance of the relevant parameter at the individual level describes specific differences associated with aging. In addition, our approach highlights white matter areas that reliably discriminate between patients with Alzheimer's disease and healthy controls with a predictive power of 0.99 and include the hippocampal alveus, the para-hippocampal white matter, the white matter of the posterior cingulate, and optic tracts. In this context, notably the classifier includes a sub-population of patients with minimal cognitive impairment into the pathological domain. Our classifier offers promising features for an accessible biomarker that predicts the risk of conversion to Alzheimer's disease. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how to apply/ADNI Acknowledgement List.pdf. Significance statement This study assesses neuro-degenerative processes in the brain's white matter as revealed by diffusion-weighted imaging, in order to discriminate healthy from pathological aging in a large sample of elderly subjects. The analysis of time-series examinations in a linear mixed effects model allowed the discrimination of population-based aging processes from individual determinants. We demonstrate that a simple classifier based on white matter imaging data is able to predict the conversion to Alzheimer's disease with a high predictive power. Copyright © 2017 Elsevier B.V. All rights reserved.

Normative development of white matter tracts: similarities and differences in relation to age, gender, and intelligence.

PubMed

Clayden, Jonathan D; Jentschke, Sebastian; Muñoz, Mónica; Cooper, Janine M; Chadwick, Martin J; Banks, Tina; Clark, Chris A; Vargha-Khadem, Faraneh

2012-08-01

The white matter of the brain undergoes a range of structural changes throughout development; from conception to birth, in infancy, and onwards through childhood and adolescence. Several studies have used diffusion magnetic resonance imaging (dMRI) to investigate these changes, but a consensus has not yet emerged on which white matter tracts undergo changes in the later stages of development or what the most important driving factors are behind these changes. In this study of typically developing 8- to 16-year-old children, we use a comprehensive data-driven approach based on principal components analysis to identify effects of age, gender, and brain volume on dMRI parameters, as well as their relative importance. We also show that secondary components of these parameters predict full-scale IQ, independently of the age- and gender-related effects. This overarching assessment of the common factors and gender differences in normal white matter tract development will help to advance understanding of this process in late childhood and adolescence.

Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study.

PubMed

Tylee, Daniel S; Kikinis, Zora; Quinn, Thomas P; Antshel, Kevin M; Fremont, Wanda; Tahir, Muhammad A; Zhu, Anni; Gong, Xue; Glatt, Stephen J; Coman, Ioana L; Shenton, Martha E; Kates, Wendy R; Makris, Nikos

2017-01-01

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1) white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2) the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF), and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.

Structural abnormality of the corticospinal tract in major depressive disorder

PubMed Central

2014-01-01

Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

Maternal adiposity negatively influences infant brain white matter development.

PubMed

Ou, Xiawei; Thakali, Keshari M; Shankar, Kartik; Andres, Aline; Badger, Thomas M

2015-05-01

To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Diffusion tensor imaging (DTI) was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age (AGA) infants from uncomplicated pregnancies of normal-weight (BMI < 25 at conception) or obese ( BMI = 30 at conception) and otherwise healthy mothers. Tract-based spatial statistics (TBSS) analyses were used for voxel-wise group comparison of fractional anisotropy (FA), a sensitive measure of white matter integrity. DNA methylation analyses of umbilical cord tissue focused on genes known to be important in CNS development were also performed. Newborns from obese women had significantly lower FA values in multiple white matter regions than those born of normal-weight mothers. Global and regional FA values negatively correlated (P < 0.05) with maternal fat mass percentage. Linear regression analysis followed by gene ontology enrichment showed that methylation status of 68 CpG sites representing 57 genes with GO terms related to CNS development was significantly associated with maternal adiposity status. These results suggest a negative association between maternal adiposity and white matter development in offspring. © 2015 The Obesity Society.

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

PubMed Central

Gillen, Kelly M.; Mubarak, Mayyan; Nguyen, Thanh D.; Pitt, David

2018-01-01

Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i.e., the rim and normal adjacent white matter of chronic active lesions. In chronic active lesions, microglia and macrophages may contain high amounts of iron, express markers of proinflammatory polarization, are activated for an extended period of time (years), and drive chronic tissue damage. Iron-positive myeloid cells can be visualized and quantified with quantitative susceptibility mapping (QSM), a magnetic resonance imaging technique. Thus, QSM has potential as an in vivo biomarker for chronic inflammatory activity in established white matter MS lesions. Reducing chronic inflammation associated with iron accumulation using existing or novel MS therapies may impact disease severity and progression. PMID:29515576

Automatic segmentation of white matter hyperintensities robust to multicentre acquisition and pathological variability

NASA Astrophysics Data System (ADS)

Samaille, T.; Colliot, O.; Cuingnet, R.; Jouvent, E.; Chabriat, H.; Dormont, D.; Chupin, M.

2012-02-01

White matter hyperintensities (WMH), commonly seen on FLAIR images in elderly people, are a risk factor for dementia onset and have been associated with motor and cognitive deficits. We present here a method to fully automatically segment WMH from T1 and FLAIR images. Iterative steps of non linear diffusion followed by watershed segmentation were applied on FLAIR images until convergence. Diffusivity function and associated contrast parameter were carefully designed to adapt to WMH segmentation. It resulted in piecewise constant images with enhanced contrast between lesions and surrounding tissues. Selection of WMH areas was based on two characteristics: 1) a threshold automatically computed for intensity selection, 2) main location of areas in white matter. False positive areas were finally removed based on their proximity with cerebrospinal fluid/grey matter interface. Evaluation was performed on 67 patients: 24 with amnestic mild cognitive impairment (MCI), from five different centres, and 43 with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoaraiosis (CADASIL) acquired in a single centre. Results showed excellent volume agreement with manual delineation (Pearson coefficient: r=0.97, p<0.001) and substantial spatial correspondence (Similarity Index: 72%+/-16%). Our method appeared robust to acquisition differences across the centres as well as to pathological variability.

Traumatic Brain Injury: Hope Through Research

MedlinePlus

... last decade to image milder TBI damage. For example, diffusion tensor imaging (DTI) can image white matter tracts, more sensitive tests like fluid-attenuated inversion recovery (FLAIR) can detect ...

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia.

PubMed

Nugent, Katie L; Chiappelli, Joshua; Sampath, Hemalatha; Rowland, Laura M; Thangavelu, Kavita; Davis, Beshaun; Du, Xiaoming; Muellerklein, Florian; Daughters, Stacey; Kochunov, Peter; Hong, L Elliot

2015-09-01

Although acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Acute and prolonged salivary cortisol response was measured outside the scanner at pretest and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n = 45) and controls (n = 53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n = 30) and controls (n = 33). Patients who did not tolerate the psychological stress task and quit had greater acute (t = 2.52 [p = .016] and t = 3.51 [p = .001] at 0 and 20 minutes) and prolonged (t = 3.62 [p = .001] at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r = -0.468, p = .009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.

White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.

PubMed

Liu, Fang; Scantlebury, Nadia; Tabori, Uri; Bouffet, Eric; Laughlin, Suzanne; Strother, Douglas; McConnell, Dina; Hukin, Juliette; Fryer, Chris; Brière, Marie-Eve; Montour-Proulx, Isabelle; Keene, Daniel; Wang, Frank; Mabbott, Donald J

2015-04-01

While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Patient-Specific Anisotropic Diffusion Model for Brain Tumour Spread.

PubMed

Swan, Amanda; Hillen, Thomas; Bowman, John C; Murtha, Albert D

2018-05-01

Gliomas are primary brain tumours arising from the glial cells of the nervous system. The diffuse nature of spread, coupled with proximity to critical brain structures, makes treatment a challenge. Pathological analysis confirms that the extent of glioma spread exceeds the extent of the grossly visible mass, seen on conventional magnetic resonance imaging (MRI) scans. Gliomas show faster spread along white matter tracts than in grey matter, leading to irregular patterns of spread. We propose a mathematical model based on Diffusion Tensor Imaging, a new MRI imaging technique that offers a methodology to delineate the major white matter tracts in the brain. We apply the anisotropic diffusion model of Painter and Hillen (J Thoer Biol 323:25-39, 2013) to data from 10 patients with gliomas. Moreover, we compare the anisotropic model to the state-of-the-art Proliferation-Infiltration (PI) model of Swanson et al. (Cell Prolif 33:317-329, 2000). We find that the anisotropic model offers a slight improvement over the standard PI model. For tumours with low anisotropy, the predictions of the two models are virtually identical, but for patients whose tumours show higher anisotropy, the results differ. We also suggest using the data from the contralateral hemisphere to further improve the model fit. Finally, we discuss the potential use of this model in clinical treatment planning.

Empirical single sample quantification of bias and variance in Q-ball imaging.

PubMed

Hainline, Allison E; Nath, Vishwesh; Parvathaneni, Prasanna; Blaber, Justin A; Schilling, Kurt G; Anderson, Adam W; Kang, Hakmook; Landman, Bennett A

2018-02-06

The bias and variance of high angular resolution diffusion imaging methods have not been thoroughly explored in the literature and may benefit from the simulation extrapolation (SIMEX) and bootstrap techniques to estimate bias and variance of high angular resolution diffusion imaging metrics. The SIMEX approach is well established in the statistics literature and uses simulation of increasingly noisy data to extrapolate back to a hypothetical case with no noise. The bias of calculated metrics can then be computed by subtracting the SIMEX estimate from the original pointwise measurement. The SIMEX technique has been studied in the context of diffusion imaging to accurately capture the bias in fractional anisotropy measurements in DTI. Herein, we extend the application of SIMEX and bootstrap approaches to characterize bias and variance in metrics obtained from a Q-ball imaging reconstruction of high angular resolution diffusion imaging data. The results demonstrate that SIMEX and bootstrap approaches provide consistent estimates of the bias and variance of generalized fractional anisotropy, respectively. The RMSE for the generalized fractional anisotropy estimates shows a 7% decrease in white matter and an 8% decrease in gray matter when compared with the observed generalized fractional anisotropy estimates. On average, the bootstrap technique results in SD estimates that are approximately 97% of the true variation in white matter, and 86% in gray matter. Both SIMEX and bootstrap methods are flexible, estimate population characteristics based on single scans, and may be extended for bias and variance estimation on a variety of high angular resolution diffusion imaging metrics. © 2018 International Society for Magnetic Resonance in Medicine.

Robust MR-based approaches to quantifying white matter structure and structure/function alterations in Huntington's disease

PubMed Central

Steventon, Jessica J.; Trueman, Rebecca C.; Rosser, Anne E.; Jones, Derek K.

2016-01-01

Background Huge advances have been made in understanding and addressing confounds in diffusion MRI data to quantify white matter microstructure. However, there has been a lag in applying these advances in clinical research. Some confounds are more pronounced in HD which impedes data quality and interpretability of patient-control differences. This study presents an optimised analysis pipeline and addresses specific confounds in a HD patient cohort. Method 15 HD gene-positive and 13 matched control participants were scanned on a 3T MRI system with two diffusion MRI sequences. An optimised post processing pipeline included motion, eddy current and EPI correction, rotation of the B matrix, free water elimination (FWE) and tractography analysis using an algorithm capable of reconstructing crossing fibres. The corpus callosum was examined using both a region-of-interest and a deterministic tractography approach, using both conventional diffusion tensor imaging (DTI)-based and spherical deconvolution analyses. Results Correcting for CSF contamination significantly altered microstructural metrics and the detection of group differences. Reconstructing the corpus callosum using spherical deconvolution produced a more complete reconstruction with greater sensitivity to group differences, compared to DTI-based tractography. Tissue volume fraction (TVF) was reduced in HD participants and was more sensitive to disease burden compared to DTI metrics. Conclusion Addressing confounds in diffusion MR data results in more valid, anatomically faithful white matter tract reconstructions with reduced within-group variance. TVF is recommended as a complementary metric, providing insight into the relationship with clinical symptoms in HD not fully captured by conventional DTI metrics. PMID:26335798

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Li, Yimei

Purpose: To determine whether radiation-induced changes in white matter tracts are uniform across the brainstem. Methods and Materials: We analyzed serial diffusion tensor imaging data, acquired before radiation therapy and over 48 to 72 months of follow-up, from 42 pediatric patients (age 6-20 years) with medulloblastoma. FSL software (FMRIB, Oxford, UK) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivities. For a consistent identification of volumes of interest (VOIs), the parametric maps of each patient were transformed to a standard brain space (MNI152), on which we identified VOIs including corticospinal tract (CST), medial lemniscus (ML), transversemore » pontine fiber (TPF), and middle cerebellar peduncle (MCP) at the level of pons. Temporal changes of DTI parameters in VOIs were compared using a linear mixed effect model. Results: Radiation-induced white matter injury was marked by a decline in FA after treatment. The decline was often accompanied by decreased axial diffusivity, increased radial diffusivity, or both. This implied axonal damage and demyelination. We observed that the magnitude of the changes was not always uniform across substructures of the brainstem. Specifically, the changes in DTI parameters for TPF were more pronounced than in other regions (P<.001 for FA) despite similarities in the distribution of dose. We did not find a significant difference among CST, ML, and MCP in these patients (P>.093 for all parameters). Conclusions: Changes in the structural integrity of white matter tracts, assessed by DTI, were not uniform across the brainstem after radiation therapy. These results support a role for tract-based assessment in radiation treatment planning and determination of brainstem tolerance.« less

Robust MR-based approaches to quantifying white matter structure and structure/function alterations in Huntington's disease.

PubMed

Steventon, Jessica J; Trueman, Rebecca C; Rosser, Anne E; Jones, Derek K

2016-05-30

Huge advances have been made in understanding and addressing confounds in diffusion MRI data to quantify white matter microstructure. However, there has been a lag in applying these advances in clinical research. Some confounds are more pronounced in HD which impedes data quality and interpretability of patient-control differences. This study presents an optimised analysis pipeline and addresses specific confounds in a HD patient cohort. 15 HD gene-positive and 13 matched control participants were scanned on a 3T MRI system with two diffusion MRI sequences. An optimised post processing pipeline included motion, eddy current and EPI correction, rotation of the B matrix, free water elimination (FWE) and tractography analysis using an algorithm capable of reconstructing crossing fibres. The corpus callosum was examined using both a region-of-interest and a deterministic tractography approach, using both conventional diffusion tensor imaging (DTI)-based and spherical deconvolution analyses. Correcting for CSF contamination significantly altered microstructural metrics and the detection of group differences. Reconstructing the corpus callosum using spherical deconvolution produced a more complete reconstruction with greater sensitivity to group differences, compared to DTI-based tractography. Tissue volume fraction (TVF) was reduced in HD participants and was more sensitive to disease burden compared to DTI metrics. Addressing confounds in diffusion MR data results in more valid, anatomically faithful white matter tract reconstructions with reduced within-group variance. TVF is recommended as a complementary metric, providing insight into the relationship with clinical symptoms in HD not fully captured by conventional DTI metrics. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach.

PubMed

Cui, Zaixu; Xia, Zhichao; Su, Mengmeng; Shu, Hua; Gong, Gaolang

2016-04-01

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. © 2016 Wiley Periodicals, Inc.

Brain white matter structure and information processing speed in healthy older age.

PubMed

Kuznetsova, Ksenia A; Maniega, Susana Muñoz; Ritchie, Stuart J; Cox, Simon R; Storkey, Amos J; Starr, John M; Wardlaw, Joanna M; Deary, Ian J; Bastin, Mark E

2016-07-01

Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (g speed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the g speed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and g speed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.

A longitudinal study of computerized cognitive training in stroke patients - effects on cognitive function and white matter.

PubMed

Nyberg, Claudia Kim; Nordvik, Jan Egil; Becker, Frank; Rohani, Darius A; Sederevicius, Donatas; Fjell, Anders M; Walhovd, Kristine B

2018-05-01

Background Computerized cognitive training is suggested to enhance attention and working memory functioning following stroke, but effects on brain and behavior are not sufficiently studied and longitudinal studies assessing brain and behavior relationships are scarce. Objective The study objectives were to investigate relations between neuropsychological performance post-stroke and white matter microstructure measures derived from diffusion tensor imaging (DTI), including changes after 6 weeks of working memory training. Methods In this experimental training study, 26 stroke patients underwent DTI and neuropsychological tests at 3 time points - before and after a passive phase of 6 weeks, and again after 6 weeks of working memory training (Cogmed QM). Fractional anisotropy (FA) was extracted from stroke-free brain areas to assess the white matter microstructure. Twenty-two participants completed the majority of training (≥18/25 sessions) and were entered into longitudinal analyses. Results Significant correlations between FA and baseline cognitive functions were observed (r = 0.58, p = 0.004), however, no evidence was found of generally improved cognitive functions following training or of changes in white matter microstructure. Conclusions While white matter microstructure related to baseline cognitive function in stroke patients, the study revealed no effect on cognitive functions or microstructural changes in white matter in relation to computerized working memory training.

Recent-onset schizophrenia and adolescent cannabis use: MRI evidence for structural hyperconnectivity?

PubMed

Peters, Bart D; de Haan, Lieuwe; Vlieger, Erik-Jan; Majoie, Charles B; den Heeten, Gerard J; Linszen, Don H

2009-01-01

There is growing evidence that brain white matter abnormalities are implicated in the pathophysiology of schizophrenia. Cannabis use is an independent risk factor for schizophrenia.We tested the hypothesis that cannabis use during early adolescence is associated with white matter abnormalities in schizophrenia patients. Thirtyfive male recent-onset schizophrenia patients, with and without a history of cannabis use before age 17, and twenty-one matched healthy comparison men without illicit drug use were assessed with diffusion tensor imaging (DTI).White matter regions of interest were examined in co-registered DTI images. Compared to controls, patients with cannabis use before age 17 showed increased directional coherence in the bilateral uncinate fasciculus, anterior internal capsule and frontal white matter. These abnormalities were absent in patients without cannabis use before age 17. The abnormalities were not related to lifetime doses of cannabis or other illicit drugs.We could not exclude confounding effects of other illicit drugs. Recent-onset schizophrenia patients with start of cannabis use during early adolescence use may represent a subgroup of schizophrenia patients with increased white matter directional coherence, which may reflect structural hyperconnectivity. This is in contrast with most DTI studies in schizophrenia, which have produced evidence for hypoconnectivity. Further studies are necessary to assess the effect of adolescent cannabis and other illicit drug use on brain white matter in schizophrenia.

Rat brain digital stereotaxic white matter atlas with fine tract delineation in Paxinos space and its automated applications in DTI data analysis.

PubMed

Liang, Shengxiang; Wu, Shang; Huang, Qi; Duan, Shaofeng; Liu, Hua; Li, Yuxiao; Zhao, Shujun; Nie, Binbin; Shan, Baoci

2017-11-01

To automatically analyze diffusion tensor images of the rat brain via both voxel-based and ROI-based approaches, we constructed a new white matter atlas of the rat brain with fine tracts delineation in the Paxinos and Watson space. Unlike in previous studies, we constructed a digital atlas image from the latest edition of the Paxinos and Watson. This atlas contains 111 carefully delineated white matter fibers. A white matter network of rat brain based on anatomy was constructed by locating the intersection of all these tracts and recording the nuclei on the pathway of each white matter tract. Moreover, a compatible rat brain template from DTI images was created and standardized into the atlas space. To evaluate the automated application of the atlas in DTI data analysis, a group of rats with right-side middle cerebral artery occlusion (MCAO) and those without were enrolled in this study. The voxel-based analysis result shows that the brain region showing significant declines in signal in the MCAO rats was consistent with the occlusion position. We constructed a stereotaxic white matter atlas of the rat brain with fine tract delineation and a compatible template for the data analysis of DTI images of the rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

White matter injury induced by diabetes in acute stroke is clinically relevant: A preliminary study.

PubMed

Yu, Xinfeng; Song, Ruirui; Jiaerken, Yerfan; Yuan, Lixia; Huang, Peiyu; Lou, Min; Jiang, Quan; Zhang, Minming

2017-01-01

The importance of white matter injury induced by diabetes in stroke severity and prognosis is largely unknown. We aimed to investigate the relationship between diabetes-related white matter injury beyond stroke lesions with acute neurological deficits and clinical outcome after stroke. In total, 36 stroke patients within 3-7 days after onset were enrolled. Neurological deficits on admission were assessed by National Institute of Health Stroke Score, and poor outcome at 3 months was defined as modified Rankin score >2. White matter tracts were compared between patients with diabetic and non-diabetic stroke using fractional anisotropy from diffusion tensor imaging. Regional white matter abnormality with decreased fractional anisotropy was observed in diabetic patients (n = 18) when compared to non-diabetic patients (n = 18). Decreased fractional anisotropy in ipsilesional distal corticospinal tract was independently associated with higher National Institute of Health Stroke Score motor component score (β = -0.444, p = 0.005), and decreased fractional anisotropy in contralesional superior longitudinal fasciculus I was independently related to poor outcome (odds ratio, 0.900; p = 0.033). Our findings suggested that only white matter injury induced by diabetes in specific tracts like corticospinal tract and superior longitudinal fasciculus beyond stroke lesions has clinically relevant, providing insight into the mechanism of stroke recovery under the diabetic condition. © The Author(s) 2016.

White matter pathway supporting phonological encoding in speech production: a multi-modal imaging study of brain damage patients.

PubMed

Han, Zaizhu; Ma, Yujun; Gong, Gaolang; Huang, Ruiwang; Song, Luping; Bi, Yanchao

2016-01-01

In speech production, an important step before motor programming is the retrieval and encoding of the phonological elements of target words. It has been proposed that phonological encoding is supported by multiple regions in the left frontal, temporal and parietal regions and their underlying white matter, especially the left arcuate fasciculus (AF) or superior longitudinal fasciculus (SLF). It is unclear, however, whether the effects of AF/SLF are indeed related to phonological encoding for output and whether there are other white matter tracts that also contribute to this process. We comprehensively investigated the anatomical connectivity supporting phonological encoding in production by studying the relationship between the integrity of all major white matter tracts across the entire brain and phonological encoding deficits in a group of 69 patients with brain damage. The integrity of each white matter tract was measured both by the percentage of damaged voxels (structural imaging) and the mean fractional anisotropy value (diffusion tensor imaging). The phonological encoding deficits were assessed by various measures in two oral production tasks that involve phonological encoding: the percentage of nonword (phonological) errors in oral picture naming and the accuracy of word reading aloud with word comprehension ability regressed out. We found that the integrity of the left SLF in both the structural and diffusion tensor imaging measures consistently predicted the severity of phonological encoding impairment in the two phonological production tasks. Such effects of the left SLF on phonological production remained significant when a range of potential confounding factors were considered through partial correlation, including total lesion volume, demographic factors, lesions on phonological-relevant grey matter regions, or effects originating from the phonological perception or semantic processes. Our results therefore conclusively demonstrate the central role of the left SLF in phonological encoding in speech production.

Metronidazole-induced encephalopathy: not always a reversible situation.

PubMed

Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna

2015-06-01

Metronidazole is a nitroimidazole antimicrobial drug prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system (CNS) toxicity manifesting as metronidazole-induced encephalopathy (MIE). Case report. A 65-year-old woman with hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive encephalopathy to GCS 4 during a 3-week course of metronidazole for cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with symmetrical T2 hyperintensity and generally restricted diffusion in bilateral dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles, internal capsules, and cerebral white matter. Laboratory values did not demonstrate significant electrolyte shifts, and continuous EEG was without seizure. High-dose thiamine was empirically administered. Lumbar puncture was not performed due to coagulopathy and thrombocytopenia. Despite discontinuation of metronidazole and keeping ammonia levels near normal, the patient did not improve. MRI was repeated 1 week after discontinuation of metronidazole. Although there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2 hyperintensity persisted and even progressed in the brainstem, basal ganglia, and subcortical white matter. Petechial hemorrhages developed in bilateral corticospinal tracts and subcortical white matter. T1 hypointensity appeared in the corpus callosum. She was transitioned to comfort measures only and died 12 days later. MIE is an uncommon adverse effect of treatment with metronidazole that characteristically affects the dentate nuclei but may also involve the brainstem, corpus callosum, subcortical white matter, and basal ganglia. While the clinical symptoms and neuroimaging changes are usually reversible, persistent encephalopathy with poor outcome may occur.

White Matter Integrity in High-Altitude Pilots Exposed to Hypobaria

PubMed Central

McGuire, Stephen A.; Boone, Goldie R.E.; Sherman, Paul M.; Tate, David F.; Wood, Joe D.; Patel, Beenish; Eskandar, George; Wijtenburg, S. Andrea; Rowland, Laura M.; Clarke, Geoffrey D.; Grogan, Patrick M.; Sladky, John H.; Kochunov, Peter V.

2017-01-01

Introduction Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. Methods There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. Results Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. Discussion Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes. PMID:28323582

Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection.

PubMed

Cordero, Daniella M; Towe, Sheri L; Chen, Nan-Kuei; Robertson, Kevin R; Madden, David J; Huettel, Scott A; Meade, Christina S

2017-06-01

This study investigated the association of HIV infection and cocaine dependence with cerebral white matter integrity using diffusion tensor imaging (DTI). One hundred thirty-five participants stratified by HIV and cocaine status (26 HIV+/COC+, 37 HIV+/COC-, 37 HIV-/COC+, and 35 HIV-/COC-) completed a comprehensive substance abuse assessment, neuropsychological testing, and MRI with DTI. Among HIV+ participants, all were receiving HIV care and 46% had an AIDS diagnosis. All COC+ participants were current users and met criteria for cocaine use disorder. We used tract-based spatial statistics (TBSS) to assess the relation of HIV and cocaine to fractional anisotropy (FA) and mean diffusivity (MD). In whole-brain analyses, HIV+ participants had significantly reduced FA and increased MD compared to HIV- participants. The relation of HIV and FA was widespread throughout the brain, whereas the HIV-related MD effects were restricted to the corpus callosum and thalamus. There were no significant cocaine or HIV-by-cocaine effects. These DTI metrics correlated significantly with duration of HIV disease, nadir CD4+ cell count, and AIDS diagnosis, as well as some measures of neuropsychological functioning. These results suggest that HIV is related to white matter integrity throughout the brain, and that HIV-related effects are more pronounced with increasing duration of infection and greater immune compromise. We found no evidence for independent effects of cocaine dependence on white matter integrity, and cocaine dependence did not appear to exacerbate the effects of HIV.

Changes of migraine-related white matter hyperintensities after 3 years: a longitudinal MRI study.

PubMed

Erdélyi-Bótor, Szilvia; Aradi, Mihály; Kamson, David Olayinka; Kovács, Norbert; Perlaki, Gábor; Orsi, Gergely; Nagy, Szilvia Anett; Schwarcz, Attila; Dóczi, Tamás; Komoly, Sámuel; Deli, Gabriella; Trauninger, Anita; Pfund, Zoltán

2015-01-01

The aim of this longitudinal study was to investigate changes of migraine-related brain white matter hyperintensities 3 years after an initial study. Baseline quantitative magnetic resonance imaging (MRI) studies of migraine patients with hemispheric white matter hyperintensities performed in 2009 demonstrated signs of tissue damage within the hyperintensities. The hyperintensities appeared most frequently in the deep white matter of the frontal lobe with a similar average hyperintensity size in all hemispheric lobes. Since in this patient group the repeated migraine attacks were the only known risk factors for the development of white matter hyperintensities, the remeasurements of migraineurs after a 3-year long follow-up may show changes in the status of these structural abnormalities as the effects of the repeated headaches. The same patient group was reinvestigated in 2012 using the same MRI scanner and acquisition protocol. MR measurements were performed on a 3.0-Tesla clinical MRI scanner. Beyond the routine T1-, T2-weighted, and fluid-attenuated inversion recovery imaging, diffusion and perfusion-weighted imaging, proton magnetic resonance spectroscopy, and T1 and T2 relaxation time measurements were also performed. Findings of the baseline and follow-up studies were compared with each other. The follow-up proton magnetic resonance spectroscopy studies of white matter hyperintensities showed significantly decreased N-acetyl-aspartate (median values 8.133 vs 7.153 mmol/L, P=.009) and creatine/phosphocreatine (median values 4.970 vs 4.641 mmol/L, P=.015) concentrations compared to the baseline, indicating a more severe axonal loss and glial hypocellularity with decreased intracellular energy production. The diffusion values, the T1 and T2 relaxation times, and the cerebral blood flow and volume measurements presented only mild changes between the studies. The number (median values 21 vs 25, P<.001) and volume (median values 0.896 vs 1.140 mL, P<.001) of hyperintensities were significantly higher in the follow-up study. No changes were found in the hemispheric and lobar distribution of hyperintensities. An increase in the hyperintensity size of preexisting lesions was much more common than a decrease (median values 14 vs 5, P=.004). A higher number of newly developed hyperintensities were detected than disappeared ones (130 vs 22), and most of them were small (<.034 mL). Small white matter hyperintensities in patients with a low migraine attack frequency had a higher chance to disappear than large white matter hyperintensities or white matter hyperintensities in patients with a high attack frequency (coefficient: -0.517, P=.034). This longitudinal MRI study found clinically silent brain white matter hyperintensities to be predominantly progressive in nature. The absence of a control group precludes definitive conclusions about the nature of these changes or if their degree is beyond normal aging. © 2014 American Headache Society.

Right-to-left shunt may be prone to affect the white matter integrity of posterior circulation in migraine without aura.

PubMed

Xie, Hui; Bian, Yitong; Jian, Zhijie; Huo, Kang; Liu, Rui; Zhu, Dan; Zhang, Lihui; Wu, Jun; Yang, Jian; Liu, Jixin; Luo, Guogang

2018-01-01

Numerous studies have indicated an association between migraine and right-to-left shunt. However, little is known about whether right-to-left shunt has an effect on the migraine brain. This observational study aims to explore the impact of right-to-left shunt on the brain of migraine without aura on microstructural level. Thirty-five patients with migraine without aura were enrolled in this study. Contrast-enhanced Transcranial Doppler was performed to evaluate the status of right-to-left shunt. Three-dimensional T1-weighted and diffusion tensor images were acquired for data analysis. We employed voxel-based morphometry and tract-based spatial statistical analyses to assess the differences of gray and white matter between migraineurs with and without right-to-left shunt, respectively. Among the 35 patients, 19 (54.3%) patients had right-to-left shunt. There were no significant differences in headache features between migraineurs with and without right-to-left shunt. There were significant increases of mean and radial diffusivity in migraineurs with right-to-left shunt compared with migraineurs without right-to-left shunt. The alterations were primarily located in the right posterior thalamic radiation, secondly in the body of corpus callosum and the right superior corona radiata. No significant differences were observed in values of fractional anisotropy and axial diffusivity. No significant between-group differences were found in gray matter volume. Right-to-left shunt may cause alterations of white matter integrity in migraine without aura, and the alterations are more likely to be located at the posterior circulation.

White Matter Microstructure in Subjects with Attention-Deficit/Hyperactivity Disorder and Their Siblings

ERIC Educational Resources Information Center

Lawrence, Katherine E.; Levitt, Jennifer G.; Loo, Sandra K.; Ly, Ronald; Yee, Victor; O'Neill, Joseph; Alger, Jeffry; Narr, Katherine L.

2013-01-01

Objective: Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed, and few studies have examined the contribution of ADHD…

Diffusion Tensor Imaging Correlates of Reading Ability in Dysfluent and Non-Impaired Readers

ERIC Educational Resources Information Center

Lebel, Catherine; Shaywitz, Bennett; Holahan, John; Shaywitz, Sally; Marchione, Karen; Beaulieu, Christian

2013-01-01

Many children and adults have specific reading disabilities; insight into the brain structure underlying these difficulties is evolving from imaging. Previous research highlights the left temporal-parietal white matter as important in reading, yet the degree of involvement of other areas remains unclear. Diffusion tensor imaging (DTI) and…

Analysis of alterations in white matter integrity of adult patients with comitant exotropia.

PubMed

Li, Dan; Li, Shenghong; Zeng, Xianjun

2018-05-01

Objective This study was performed to investigate structural abnormalities of the white matter in patients with comitant exotropia using the tract-based spatial statistics (TBSS) method. Methods Diffusion tensor imaging data from magnetic resonance images of the brain were collected from 20 patients with comitant exotropia and 20 age- and sex-matched healthy controls. The FMRIB Software Library was used to compute the diffusion measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). These measures were obtained using voxel-wise statistics with threshold-free cluster enhancement. Results The FA values in the right inferior fronto-occipital fasciculus (IFO) and right inferior longitudinal fasciculus were significantly higher and the RD values in the bilateral IFO, forceps minor, left anterior corona radiata, and left anterior thalamic radiation were significantly lower in the comitant exotropia group than in the healthy controls. No significant differences in the MD or AD values were found between the two groups. Conclusions Alterations in FA and RD values may indicate the underlying neuropathologic mechanism of comitant exotropia. The TBSS method can be a useful tool to investigate neuronal tract participation in patients with this disease.

Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes.

PubMed

King, Tricia Z; Wang, Liya; Mao, Hui

2015-01-01

Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use. PMID:24131511

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

PubMed

Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

2013-10-17

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

Frontostriatal anatomical connections predict age- and difficulty-related differences in reinforcement learning.

PubMed

van de Vijver, Irene; Ridderinkhof, K Richard; Harsay, Helga; Reneman, Liesbeth; Cavanagh, James F; Buitenweg, Jessika I V; Cohen, Michael X

2016-10-01

Reinforcement learning (RL) is supported by a network of striatal and frontal cortical structures that are connected through white-matter fiber bundles. With age, the integrity of these white-matter connections declines. The role of structural frontostriatal connectivity in individual and age-related differences in RL is unclear, although local white-matter density and diffusivity have been linked to individual differences in RL. Here we show that frontostriatal tract counts in young human adults (aged 18-28), as assessed noninvasively with diffusion-weighted magnetic resonance imaging and probabilistic tractography, positively predicted individual differences in RL when learning was difficult (70% valid feedback). In older adults (aged 63-87), in contrast, learning under both easy (90% valid feedback) and difficult conditions was predicted by tract counts in the same frontostriatal network. Furthermore, network-level analyses showed a double dissociation between the task-relevant networks in young and older adults, suggesting that older adults relied on different frontostriatal networks than young adults to obtain the same task performance. These results highlight the importance of successful information integration across striatal and frontal regions during RL, especially with variable outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Progression of white matter damage in progressive supranuclear palsy with predominant parkinsonism.

PubMed

Caso, Francesca; Agosta, Federica; Ječmenica-Lukić, Milica; Petrović, Igor; Meani, Alessandro; Kostic, Vladimir S; Filippi, Massimo

2018-04-01

Progressive supranuclear palsy with predominant parkinsonism (PSP-P) accounts for 14-35% of all PSP cases. A few cross-sectional MRI studies in PSP-P showed a remarkable white matter (WM) damage. Progression of brain structural damage in these patients remains unknown. Longitudinal clinical, cognitive and diffusion tensor (DT) MRI data were obtained over a mean 1.6 year follow up in 10 PSP-P patients. At study entry, patients were compared with 36 healthy controls. Voxelwise statistical analysis of white matter DT MRI data (mean, axial and radial diffusivity, and fractional anisotropy) was carried out using tract-based spatial statistics. During the 1.6 year follow up, PSP-P patients showed significant decline of motor, cognitive and mood disturbances. DT MRI analysis revealed at baseline a widespread pattern of WM alterations. Over time, PSP-P patients exhibited progression of WM damage in supratentorial tracts compared to baseline. No WM changes were detected in cerebellar WM. In PSP-P patients, WM damage significantly progressed over time. Longitudinal DT MRI measures are a potential in vivo marker of disease progression in PSP-P. Copyright © 2018 Elsevier Ltd. All rights reserved.

[CADASIL with cysteine-sparing NOTCH3 mutation manifesting as dissociated progression between cognitive impairment and brain image findings in 3 years: A case report].

PubMed

Tachiyama, Keisuke; Shiga, Yuji; Shimoe, Yutaka; Mizuta, Ikuko; Mizuno, Toshiki; Kuriyama, Masaru

2018-04-25

A 55-year-old man with no history of stroke or migraine presented to the clinic with cognitive impairment and depression that had been experiencing for two years. Neurological examination showed bilateral pyramidal signs, and impairments in cognition and attention. Brain MRI revealed multiple lacunar lesions and microbleeds in the deep cerebral white matter, subcortical regions, and brainstem, as well as diffuse white matter hyperintensities without anterior temporal pole involvement. Cerebral single-photon emission computed tomography (SPECT) revealed bilateral hypoperfusion in the basal ganglia. Gene analysis revealed an arginine-to-proline missense mutation in the NOTCH3 gene at codon 75. The patient was administered lomerizine (10 mg/day), but the patient's cognitive impairment and cerebral atrophy continued to worsen. Follow-up testing with MRI three years after his initial diagnosis revealed similar lacunar infarctions, cerebral microbleeds, and diffuse white matter hyperintensities to those observed three years earlier. However, MRI scans revealed signs of increased cerebral blood flow. Together, these findings suggest that the patient's cognitive impairments may have been caused by pathogenesis in the cerebral cortex.

Structural differences in interictal migraine attack after epilepsy: A diffusion tensor imaging analysis.

PubMed

Huang, Qi; Lv, Xin; He, Yushuang; Wei, Xing; Ma, Meigang; Liao, Yuhan; Qin, Chao; Wu, Yuan

2017-12-01

Patients with epilepsy (PWE) are more likely to suffer from migraine attack, and aberrant white matter (WM) organization may be the mechanism underlying this phenomenon. This study aimed to use diffusion tensor imaging (DTI) technique to quantify WM structural differences in PWE with interictal migraine. Diffusion tensor imaging data were acquired in 13 PWE with migraine and 12 PWE without migraine. Diffusion metrics were analyzed using tract-atlas-based spatial statistics analysis. Atlas-based and tract-based spatial statistical analyses were conducted for robustness analysis. Correlation was explored between altered DTI metrics and clinical parameters. The main results are as follows: (i) Axonal damage plays a key role in PWE with interictal migraine. (ii) Significant diffusing alterations included higher fractional anisotropy (FA) in the fornix, higher mean diffusivity (MD) in the middle cerebellar peduncle (CP), left superior CP, and right uncinate fasciculus, and higher axial diffusivity (AD) in the middle CP and right medial lemniscus. (iii) Diffusion tensor imaging metrics has the tendency of correlation with seizure/migraine type and duration. Results indicate that characteristic structural impairments exist in PWE with interictal migraine. Epilepsy may contribute to migraine by altering WMs in the brain stem. White matter tracts in the fornix and right uncinate fasciculus also mediate migraine after epilepsy. This finding may improve our understanding of the pathological mechanisms underlying migraine attack after epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Hybrid Diffusion Imaging in Mild Traumatic Brain Injury.

PubMed

Wu, Yu-Chien; Mustafi, Sourajit Mitra; Harezlak, Jaroslaw; Kodiweera, Chandana; Flashman, Laura A; McAllister, Thomas

2018-05-22

Mild traumatic brain injury (mTBI) is an important public health problem. Although conventional medical imaging techniques can detect moderate-to-severe injuries, they are relatively insensitive to mTBI. In this study, we used hybrid diffusion imaging (HYDI) to detect white-matter alterations in nineteen patients with mTBI and 23 other trauma-control patients. Within 15 days (SD=10) of brain injury, all subjects underwent magnetic-resonance HYDI and were assessed with battery of neuropsychological tests of sustained attention, memory, and executive function. Tract-based spatial statistics (TBSS) were used for voxelwise statistical analyses within the white-matter skeleton to study between-group differences in diffusion metrics, within-group correlations between diffusion metrics and clinical outcomes, and between group interaction effects. The advanced diffusion imaging techniques including neurite orientation dispersion and density imaging (NODDI) and q-space analyses appeared to be more sensitive then classic diffusion tensor imaging (DTI). Only NODDI-derived intra-axonal volume fraction (V_ic) demonstrated significant group differences (i.e., 5% to 9% lower in the injured brain). Within the mTBI group, V_ic and a q-space measure, P₀, correlated with 6 of 10 neuropsychological tests including measures of attention, memory, and executive function. In addition, the direction of correlations differed significantly between the groups (R² > 0.71 and P_interation < 0.03). Specifically, in the control group, higher V_ic and P₀ were associated with better performances on clinical assessments, whereas in the mTBI group, higher V_ic and P₀ were associated with worse performances with correlation coefficients > 0.83. In summary, the NODDI-derived axonal density index and q-space measure for tissue restriction demonstrated superior sensitivity to white-matter changes shortly after mTBI. These techniques hold promise as a neuroimaging biomarker for mTBI.

Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity.

PubMed

van Leijsen, Esther M C; Bergkamp, Mayra I; van Uden, Ingeborg W M; Ghafoorian, Mohsen; van der Holst, Helena M; Norris, David G; Platel, Bram; Tuladhar, Anil M; de Leeuw, Frank-Erik

2018-05-03

White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH. NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time. Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity. © 2018 American Heart Association, Inc.

Military blast exposure, ageing and white matter integrity

PubMed Central

Trotter, Benjamin B.; Robinson, Meghan E.; Milberg, William P.; McGlinchey, Regina E.

2015-01-01

Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure—one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan—is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure × age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a ‘dose-response’ relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast-exposed group, suggesting a specific influence of time since exposure on tissue structure, and this effect was also independent of post-traumatic stress symptoms. Overall, these data suggest that blast exposure may negatively affect brain-ageing trajectories at the microstructural tissue level. Additional work examining longitudinal changes in brain tissue integrity in individuals exposed to military blast forces will be an important future direction to the initial findings presented here. PMID:26033970

White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration

PubMed Central

Downey, Laura E.; Mahoney, Colin J.; Buckley, Aisling H.; Golden, Hannah L.; Henley, Susie M.; Schmitz, Nicole; Schott, Jonathan M.; Simpson, Ivor J.; Ourselin, Sebastien; Fox, Nick C.; Crutch, Sebastian J.; Warren, Jason D.

2015-01-01

Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries. PMID:26236629

Does the use of hormonal contraceptives cause microstructural changes in cerebral white matter? Preliminary results of a DTI and tractography study.

PubMed

De Bondt, Timo; Van Hecke, Wim; Veraart, Jelle; Leemans, Alexander; Sijbers, Jan; Sunaert, Stefan; Jacquemyn, Yves; Parizel, Paul M

2013-01-01

To evaluate the effect of monophasic combined oral contraceptive pill (COCP) and menstrual cycle phase in healthy young women on white matter (WM) organization using diffusion tensor imaging (DTI). Thirty young women were included in the study; 15 women used COCP and 15 women had a natural cycle. All subjects underwent DTI magnetic resonance imaging during the follicular and luteal phase of their cycle, or in different COCP cycle phases. DTI parameters were obtained in different WM structures by performing diffusion tensor fibre tractography. Fractional anisotropy and mean diffusivity were calculated for different WM structures. Hormonal plasma concentrations were measured in peripheral venous blood samples and correlated with the DTI findings. We found a significant difference in mean diffusivity in the fornix between the COCP and the natural cycle group. Mean diffusivity values in the fornix were negatively correlated with luteinizing hormone and estradiol blood concentrations. An important part in the limbic system, the fornix, regulates emotional processes. Differences in diffusion parameters in the fornix may contribute to behavioural alternations related to COCP use. This finding also suggests that the use of oral contraceptives needs to be taken into account when designing DTI group studies.

A rare case of short stature: Say Meyer syndrome.

PubMed

Karthik, T S; Prasad, N Rajendra; Rani, P Radha; Maheshwari, Rushikesh; Reddy, P Amaresh; Chakradhar, B V S; Menon, Bindu

2013-10-01

Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. We are reporting a case of Say Meyer syndrome presented to our hospital for short stature and developmental delay at age 3½ years. A 3½-year-old boy presented to our hospital for decreased growth velocity from the age of 1 year. History revealed the boy had a birth weight of 2.3 kg, had an episode of seizures in the neonatal period. He was born to non-consanguineous marriage. He had global developmental delay and there was a lack of bowel and bladder control. History did not reveal any hearing or visual impairment. No history of any chronic systemic illnesses. Magnetic resonance imaging (MRI) brain revealed mild diffuse frontotemporal atrophy with multiple irregular gliotic areas in bilateral frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres. Diffuse thinning of corpus callosum. Diffuse periventricular hyper intensity on T2W and fluid attenuated inversion recovery sequences. Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. Characteristic MRI brain findings include diffuse frontotemporal atrophy with multiple gliotic areas in frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres.