Diffusivity In White Matter Tracts Research Articles

Multimodal MRI and tau PET findings from the Autosomal Dominant Alzheimer’s disease cohort caused by the A431E PSEN1 Jalisco mutation

AbstractBackgroundThe A431E mutation in PSEN1 is a cause of Autosomal Dominant Alzheimer’s disease (ADAD) that represents a founder effect, apparently arising from the state of Jalisco, Mexico, with over 100 superficially distinct families being affected. The median age of symptom onset is 41 years, with about 40% of cases having an atypical presentation of substantial spastic paraparesis. This study aimed to identify the neuroimaging features associated with the A431E PSEN1 Jalisco mutation to elucidate its pathophysiology and to inform future clinical studies.MethodThirty‐one participants with or known to be at‐risk for the A431E PSEN1 mutation were enrolled in a comprehensive genetic, clinical, and imaging protocol including MRI and flortaucipir PET scans. Diffusion MRI and flortaucipir PET studies were conducted on sub‐samples of the cohort along with appropriate control participants.ResultPeak flortaucipir standard uptake value ratio (SUVR) among A431E mutation carriers was predominantly in the lateral parietal cortices relative to the medial temporal lobes with disproportionate signal in motor and sensory cortex relative to persons with late onset AD. Flortaucipir SUVR in 6 brain regions (i.e., medial orbitofrontal, caudal and rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were associated with neuropsychiatric symptoms in persons with or at risk for the A431E PSEN1 mutation. Among 21 A431E PSEN1 mutation carriers with available diffusion MRI images, the Ashworth score of spastic paraparesis correlated with mean diffusivity in several brain regions, particularly left inferior parietal, superior parietal, and paracentral lobules (r’s>0.8, p’s< 0.001). In a subset of 10 clinically impaired A431E PSEN1 mutation carriers, mean diffusivity in white matter tracts underlying multiple cortical areas was higher relative to 8 impaired persons with late onset AD or ADAD mutations that do not cause spastic paraparesis.ConclusionThe pattern of flortaucipir distribution was atypical with disproportionate involvement of sensorimotor areas and parietal cortex. Higher flortaucipir signal was associated with more neuropsychiatric symptoms. Microstructural changes in white matter were more pronounced in persons with the A431E PSEN1 mutation and likely underlie the associated spastic paraparesis. The distinct neuroimaging features and associated neuropsychiatric manifestations observed in this cohort highlight the importance of comprehensively characterizing heterogeneous AD subtypes.

Multimodal MRI and tau PET findings from the Autosomal Dominant Alzheimer’s disease cohort caused by the A431E PSEN1 Jalisco mutation

AbstractBackgroundThe A431E mutation in PSEN1 is a cause of Autosomal Dominant Alzheimer’s disease (ADAD) that represents a founder effect, apparently arising from the state of Jalisco, Mexico, with over 100 superficially distinct families being affected. The median age of symptom onset is 41 years, with about 40% of cases having an atypical presentation of substantial spastic paraparesis. This study aimed to identify the neuroimaging features associated with the A431E PSEN1 Jalisco mutation to elucidate its pathophysiology and to inform future clinical studies.MethodThirty‐one participants with or known to be at‐risk for the A431E PSEN1 mutation were enrolled in a comprehensive genetic, clinical, and imaging protocol including MRI and flortaucipir PET scans. Diffusion MRI and flortaucipir PET studies were conducted on sub‐samples of the cohort along with appropriate control participants.ResultPeak flortaucipir standard uptake value ratio (SUVR) among A431E mutation carriers was predominantly in the lateral parietal cortices relative to the medial temporal lobes with disproportionate signal in motor and sensory cortex relative to persons with late onset AD. Flortaucipir SUVR in 6 brain regions (i.e., medial orbitofrontal, caudal and rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were associated with neuropsychiatric symptoms in persons with or at risk for the A431E PSEN1 mutation. Among 21 A431E PSEN1 mutation carriers with available diffusion MRI images, the Ashworth score of spastic paraparesis correlated with mean diffusivity in several brain regions, particularly left inferior parietal, superior parietal, and paracentral lobules (r’s>0.8, p’s< 0.001). In a subset of 10 clinically impaired A431E PSEN1 mutation carriers, mean diffusivity in white matter tracts underlying multiple cortical areas was higher relative to 8 impaired persons with late onset AD or ADAD mutations that do not cause spastic paraparesis.ConclusionThe pattern of flortaucipir distribution was atypical with disproportionate involvement of sensorimotor areas and parietal cortex. Higher flortaucipir signal was associated with more neuropsychiatric symptoms. Microstructural changes in white matter were more pronounced in persons with the A431E PSEN1 mutation and likely underlie the associated spastic paraparesis. The distinct neuroimaging features and associated neuropsychiatric manifestations observed in this cohort highlight the importance of comprehensively characterizing heterogeneous AD subtypes.

Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention deficit/hyperactivity disorder

BackgroundDevelopmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored.MethodsParticipants were 3rd and 4th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants.ResultsDD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found.ConclusionsFindings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD.

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate β values and 95% CI. After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (β -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend < .05), except for FA values in projection fibers. These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.

Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia

BackgroundUsing multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD). MethodTwenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity. ResultsBilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes. ConclusionsUsing multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.

Neuroimaging correlates of brain injury in Wilson's disease: a multimodal, whole-brain MRI study.

Wilson’s disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to ‘de-copper’ patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focused on specific sequences or regions of interest, often stratifying chronically treated patients according to persisting symptoms as opposed to initial presentation.In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively recruited patients with Wilson’s disease (age range 16–68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding 6 months as having ‘active’ disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically treated, stable patients.Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound (‘free’) copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically treated patients.Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson’s disease.

Canonical correlation analysis for elliptical copulas

Canonical correlation analysis (CCA) is a common method used to estimate the associations between two different sets of variables by maximizing the Pearson correlation between linear combinations of the two sets of variables. We propose a version of CCA for transelliptical distributions with an elliptical copula using pairwise Kendall’s tau to estimate a latent scatter matrix. Because Kendall’s tau relies only on the ranks of the data this method does not make any assumptions about the marginal distributions of the variables, and is valid when moments do not exist. We establish consistency and asymptotic normality for canonical directions and correlations estimated using Kendall’s tau. Simulations indicate that this estimator outperforms standard CCA for data generated from heavy tailed elliptical distributions. Our method also identifies more meaningful relationships when the marginal distributions are skewed. We also propose a method for testing for non-zero canonical correlations using bootstrap methods. This testing procedure does not require any assumptions on the joint distribution of the variables and works for all elliptical copulas. This is in contrast to permutation tests which are only valid when data are generated from a distribution with a Gaussian copula. This method’s practical utility is shown in an analysis of the association between radial diffusivity in white matter tracts and cognitive tests scores for six-year-old children from the Early Brain Development Study at UNC-Chapel Hill. An R package implementing this method is available at github.com/blangworthy/transCCA.

Differential effects of cannabis exposure during early versus later adolescence on the expression of psychosis in homeless and precariously housed adults

Longitudinal studies of cannabis exposure during early adolescence in the general population frequently report an increased risk of subsequently developing psychotic symptoms or a psychotic illness. However, there is a dearth of knowledge about the effects of early cannabis exposure on psychosis in homeless and precariously housed adults, who represent a population afflicted with high rates of psychosis. The aim of the present study was to examine how early cannabis exposure (by age 15) compared to later first use (after age 15) affected the expression of adult psychosis in this population. Secondary measures of psychopathology, drug use, cognition and brain structure were also collected. 437 subjects were recruited from single room occupancy hotels in the urban setting of the Downtown Eastside of Vancouver, Canada. Psychiatric diagnoses were determined, and psychotic symptom severity was measured with the 5-factor PANSS. Participants completed a battery of neurocognitive tests, and brain structure was assessed using structural and diffusion tensor imaging MRI scans. Results indicated that early cannabis exposure was associated with an increased risk (OR = 1.09, p < .05) of developing substance induced psychosis, whereas later first use increased risk (OR = 2.19, p < .01) of developing schizophrenia or schizoaffective disorder. There was no group difference in neurocognitive function, although differences were observed in the lateral orbitofrontal cortex and white matter tract diffusivity. These findings indicate that early cannabis exposure in this population may increase the risk of developing drug associated psychoses, which could potentially be mediated in part through altered neurodevelopmental brain changes.

Effect of age and neurofibromatosis type 1 status on white matter integrity in the optic radiations.

BackgroundAdults with neurofibromatosis type 1 (NF1) have decreased white matter integrity, but differences in children with NF1 have not been described. Defining normal values for diffusion tensor imaging (DTI) measures, especially in the optic radiations, is important to the development of DTI as a potential biomarker of visual acuity in children with optic pathway glioma. This study examines the effect of age and NF1 status on DTI measures in children.MethodsIn this retrospective study, MR imaging including DTI was conducted in 93 children (40 children with NF1 and 53 healthy controls) between 0 and 14 years of age. Regression models of age, sex, and NF1 status on DTI measures were evaluated, and tract-based spatial statistics (TBSS) compared DTI measures in age-matched NF1 to non-NF1 cohorts.ResultsFractional anisotropy, radial diffusivity, and mean diffusivity in white matter tracts of the optic radiations varied with age and were best modeled by a logarithmic function. Age-related DTI measure change was different in NF1 versus non-NF1 subjects. Normal values and 95% confidence intervals for age 0.5–12 years were derived for both groups. Differences in DTI measures between NF1 and non-NF1 groups at a range of ages were shown diffusely throughout the cerebral white matter using TBSS.ConclusionsChildren with NF1 demonstrate increased diffusion throughout the brain compared to children without NF1 suggesting a potentially altered developmental trajectory of optic radiation microstructure. Defining normal values for white matter integrity in children with NF1 may help target early intervention efforts in this vulnerable group.

Neuroradiological Changes Following Single or Repetitive Mild TBI.

ObjectivesTo test the hypothesis that there are differences in neuroradiological measures between single and repeated mild traumatic brain injury using multimodal MRI.MethodsA closed-head momentum exchange model was used to produce one or three mild head injuries in young adult male rats compared to non-injured, age and weight-matched controls. Six–seven weeks post-injury, rats were studied for deficits in cognitive and motor function. Seven–eight weeks post-injury changes in brain anatomy and function were evaluated through analysis of high resolution T2 weighted images, resting-state BOLD functional connectivity, and diffusion weighted imaging with quantitative anisotropy.ResultsHead injuries occurred without skull fracture or signs of intracranial bleeding or contusion. There were no significant differences in cognitive or motors behaviors between experimental groups. With a single mild hit, the affected areas were limited to the caudate/putamen and central amygdala. Rats hit three times showed altered diffusivity in white matter tracts, basal ganglia, central amygdala, brainstem, and cerebellum. Comparing three hits to one hit showed a similar pattern of change underscoring a dose effect of repeated head injury on the brainstem and cerebellum. Disruption of functional connectivity was pronounced with three mild hits. The midbrain dopamine system, hippocampus, and brainstem/cerebellum showed hypoconnectivity. Interestingly, rats exposed to one hit showed enhanced functional connectivity (or hyperconnectivity) across brain sites, particularly between the olfactory system and the cerebellum.InterpretationNeuroradiological evidence of altered brain structure and function, particularly in striatal and midbrain dopaminergic areas, persists long after mild repetitive head injury. These changes may serve as biomarkers of neurodegeneration and risk for dementia later in life.

Prenatal Bisphenol A Exposure and Brain Structure in Preschool-Aged Children

Background/Aim: In Canada, over 90% of the population has detectable levels of bisphenol A (BPA) due to dietary and non-dietary exposure. Human epidemiological studies have demonstrated behavioral effects of BPA exposure in children. Further, reported effects have been found to be sex-specific. Although behavioral outcomes have been examined, there is limited understanding of the effects of BPA exposure on children&amp;#8217;s brain structure. This study examined the effects of maternal BPA exposure on subsequent child white matter brain structure at 3 to 6 years of age.Method: Maternal total BPA concentrations in spot urine samples obtained during the second trimester of pregnancy were analyzed for 99 women. Their children participated in magnetic resonance imaging (MRI) between 3 to 6 years of age. Associations between prenatal BPA exposure and child fractional anisotropy and mean diffusivity within 10 isolated white matter tracts were investigated, controlling for sex and total maternal creatinine levels. Anisotropy and diffusivity provide measures of white matter structure and maturity.Results: Significant positive associations were observed between the level of prenatal BPA exposure and child white matter mean diffusivity within the splenium, and the right inferior frontal occipital, inferior longitudinal fasciculus, uncinated fasciculi, and pyramidal fibers. Significant sex differences were found, with more associations noted among females. No associations were observed between prenatal BPA exposure and child white matter anisotropy.Conclusions: Higher prenatal BPA exposure was related to higher mean diffusivity in white matter tracts at 3 to 6 years of age. Developmental studies show that with age, white matter anisotropy increases and diffusivity decreases in typically developing children. The current findings suggest that exposure to higher levels of BPA prenatally may be related to reduced white matter maturity in preschool aged children.

Thinner retinal layers are associated with changes in the visual pathway: A population-based study.

Increasing evidence shows that thinner retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), assessed on optical coherence tomography (OCT), are reflecting global brain atrophy. Yet, little is known on the relation of these layers with specific brain regions. Using voxel-based analysis, we aimed to unravel specific brain regions associated with these retinal layers. We included 2,235 persons (mean age: 67.3 years, 55% women) from the Rotterdam Study (2007-2012) who had gradable retinal OCT images and brain magnetic resonance imaging (MRI) scans, including diffusion tensor (DT) imaging. Thicknesses of peripapillary RNFL and perimacular GCL were measured using an automated segmentation algorithm. Voxel-based morphometry protocols were applied to process DT-MRI data. We investigated the association between retinal layer thickness with voxel-wise gray matter density and white matter microstructure by performing linear regression models. We found that thinner RNFL and GCL were associated with lower gray matter density in the visual cortex, and with lower fractional anisotropy and higher mean diffusivity in white matter tracts that are part of the optic radiation. Furthermore, thinner GCL was associated with lower gray matter density of the thalamus. Thinner RNFL and GCL are associated with gray and white matter changes in the visual pathway suggesting that retinal thinning on OCT may be specifically associated with changes in the visual pathway rather than with changes in the global brain. These findings may serve as a basis for understanding visual symptoms in elderly patients, patients with Alzheimer's disease, or patients with posterior cortical atrophy.

Cross-sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease.

Diffusivity in white-matter tracts is abnormal throughout the brain in cross-sectional studies of prodromal Huntington's disease. To date, longitudinal changes have not been observed. The present study investigated cross-sectional and longitudinal changes in white-matter diffusivity in relationship to the phase of prodromal Huntington's progression, and compared them with changes in brain volumes and clinical variables that track disease progression. Diffusion MRI profiles were studied for 2 years in 37 gene-negative controls and 64 prodromal Huntington's disease participants in varied phases of disease progression. To estimate the relative importance of diffusivity metrics in the prodromal phase, group effects were rank ordered relative to those obtained from analyses of brain volumes, motor, cognitive, and sensory variables. First, at baseline diffusivity was abnormal throughout all tracts, especially as individuals approached a manifest Huntington's disease diagnosis. Baseline diffusivity metrics in 6 tracts and basal ganglia volumes best distinguished among the groups. Second, group differences in longitudinal change in diffusivity were localized to the superior fronto-occipital fasciculus, most prominently in individuals closer to a diagnosis. Group differences were also observed in longitudinal changes of most brain volumes, but not clinical variables. Last, increases in motor symptoms across time were associated with greater changes in the superior fronto-occipital fasciculus diffusivity and corpus callosum, cerebrospinal fluid, and lateral ventricle volumes. These novel findings provide new insights into changes within 2 years in different facets of brain structure and their clinical relevance to changes in symptomatology that is decisive for a manifest Huntington's diagnosis. © 2016 International Parkinson and Movement Disorder Society.

Early postnatal docosahexaenoic acid levels and improved preterm brain development

BackgroundPreterm birth has a dramatic impact on polyunsaturated fatty acid exposures for the developing brain. This study examined the association between postnatal fatty acid levels and measures of brain injury and development, as well as outcomes.MethodsA cohort of 60 preterm newborns (24–32 weeks GA) was assessed using early and near-term MRI studies. Red blood cell fatty acid composition was analyzed coordinated with each scan. Outcome at a mean of 33 months corrected age was assessed using the Bayley Scales of Infant Development, 3rd edition.ResultsAdjusting for confounders, a 1% increase in postnatal docosahexaenoic acid (DHA) levels at early MRI was associated with 4.3-fold decreased odds of intraventricular hemorrhage, but was not associated with white matter injury or cerebellar haemorrhage. Higher DHA and lower linoleic acid (LA) levels at early MRI were associated with lower diffusivity in white matter tracts, and corresponding improved developmental scores in follow-up.ConclusionHigher DHA and lower LA levels in the first few weeks of life are associated with decreased IVH, improved microstructural brain development, and improved outcomes in preterm born children. Early, and possibly antenatal, intervention in high-risk pregnancies needs to be studied for potential benefits in preterm developmental outcomes.

Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema

The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA) and increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice.

Individual differences in regional prefrontal gray matter morphometry and fractional anisotropy are associated with different constructs of executive function

Although the relationship between structural differences within the prefrontal cortex (PFC) and executive function (EF) has been widely explored in cognitively impaired populations, little is known about this relationship in healthy young adults. Using optimized voxel-based morphometry (VBM), surface-based morphometry (SBM), and fractional anisotropy (FA) we determined the association between regional PFC grey matter (GM) morphometry and white matter tract diffusivity with performance on tasks that tap different aspects of EF as drawn from Miyake et al.'s three-factor model of EF. Reductions in both GM volume (VBM) and cortical folding (SBM) in the ventromedial PFC (vmPFC), ventrolateral PFC (vlPFC), and dorsolateral PFC (dlPFC) predicted better common EF, shifting-specific, and updating-specific performance, respectively. Despite capturing different components of GM morphometry, voxel- and surface-based findings were highly related, exhibiting regionally overlapping relationships with EF. Increased white matter FA in fiber tracts that connect the vmPFC and vlPFC with posterior regions of the brain also predicted better commonEF and shifting-specific performance, respectively. These results suggest that the neural mechanisms supporting distinct aspects of EF may differentially rely on distinct regions of the PFC, and at least in healthy young adults, are influenced by regional morphometry of the PFC and the FA of major white matter tracts that connect the PFC with posterior cortical and subcortical regions.

Diffusion tensor imaging comparison of progressive supranuclear palsy and corticobasal syndromes

BackgroundCorticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS) are atypical parkinsonian syndromes that are both associated with white matter tract degeneration. However, little is known about how patterns of degeneration compare across these two syndromes. MethodsTwenty-seven subjects, nine with CBS and eighteen with probable or definite PSPS (9 pathologically confirmed) were prospectively recruited and underwent 3.0 T diffusion tensor imaging. A whole-brain voxel-based analysis was performed on fractional anisotropy (FA) and mean diffusivity (MD) images to compare both groups to each other and to 50 healthy controls. ResultsThe two syndromes showed overlapping regions of reduced FA and increased MD in the body of the corpus callosum, middle cingulum bundle, and premotor and prefrontal white matter, with reduced FA also observed in the superior cerebellar peduncles in both syndromes. However, CBS showed a more supratentorial and posterior pattern of degeneration with greater involvement of the splenium of the corpus callosum, premotor, motor and parietal lobes than PSPS. Findings in CBS were also highly asymmetric. Conversely, PSPS showed a more symmetric and infratentorial pattern of degeneration, with greater involvement of the superior cerebellar peduncles and midbrain than CBS. ConclusionsCBS and PSPS are both associated with striking white matter tract degeneration. Despite differences in the supratentorial and infratentorial distribution of degeneration, and in asymmetry, both tend to target a common structural network. Measurements of white matter tract diffusion could therefore be useful disease biomarkers in both of these syndromes.

White matter tract diffusion measurements in the general population

White matter tract diffusion measurements in the general population

Diffusion tensor imaging in autism spectrum disorder: a review.

White matter tracts of the brain allow neurons and neuronal networks to communicate and function with high efficiency. The aim of this review is to briefly introduce diffusion tensor imaging methods that examine white matter tracts and then to give an overview of the studies that have investigated white matter integrity in the brains of individuals with autism spectrum disorder (ASD). From the 48 studies we reviewed, persons with ASD tended to have decreased fractional anisotropy and increased mean diffusivity in white matter tracts spanning many regions of the brain but most consistently in regions such as the corpus callosum, cingulum, and aspects of the temporal lobe. This decrease in fractional anisotropy was often accompanied by increased radial diffusivity. Additionally, the review suggests possible atypical lateralization in some white matter tracts of the brain and a possible atypical developmental trajectory of white matter microstructure in persons with ASD. Clinical implications and future research directions are discussed.