Multicenter stability of diffusion tensor imaging measures: A European clinical and physical phantom study

Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficient of variation (CV) of FA was 6.9% for the physical phantom data. The mean CV across the multicenter brain scans was 14% for tract based statistics, and 29% for deformation based analysis. The degree of variation was higher in less organized fiber tracts. Our findings suggest that a clinical and physical phantom study involving more than two scanners is indispensable to detect potential sources of bias and to reliably estimate effect size in multicenter diagnostic trials using DTI.     

Atypical white matter microstructure in left-handed individuals

Information regarding anatomical connectivity in the human brain can be gathered using diffusion tensor imaging (DTI). Fractional anisotropy (FA) is the most commonly derived value, and reflects how strongly directional are the underlying tracts. Differences in FA are thus associated with differences in the underlying microstructure of the brain. The relationships between these differences in microstructure and functional differences in corresponding regions have also been examined. Previous studies have found an effect of handedness on functional lateralization in the brain and corresponding microstructural differences. Here, using tract-based spatial statistics to analyse DTI-derived FA values, we further investigated the structural white matter architecture in the brains of right- and left-handed males. We found significantly higher FA values for left-handed, relatively to right-handed, individuals, in all major lobes, and in the corpus callosum. In support of previous suggestions, we find that there is a difference in the microstructure of white matter in left- and right-handed males that could underpin reduced lateralization of function in left-handed individuals.     

Quantitative white matter analysis by diffusion tensor imaging and potential functional correlation

Diffusion tensor imaging (DTI) is an MRI modality used to measure the thermal motion of water molecules by combining the measured water diffusion with a simple tensor model of a 3 × 3 symmetric matrix. Since there are many structures that restrict the free motion of water molecules in the brain, we can use the diffusion property of water to study the brain anatomy. Because DTI can provide directional information about axonal fiber bundles, this technique may be one of the most effective MR tools for the investigation of the human white matter anatomy in vivo. Along with the qualitative analysis of fiber pathways using tractography, the quantitative analysis using DTI enables researchers to investigate relationships between white matter anatomy and brain functions as well as to identify tract-specific developmental patterns or disease-specific alterations of the fiber tracts. Several methods have been proposed for whole-brain DTI analysis without an a priori hypothesis. Voxel-based analysis (VBA) is one of the most widely used approaches, although it has concerning limitations, especially when isotropic spatial smoothing is applied. Alternative methods such as tract-based spatial statistics and atlas-based analysis have been introduced to overcome the limitations of VBA. Future studies combining the anatomical connectivity illustrated by using DTI and the functional connectivity illustrated by using resting-state fMRI will provide an emerging landscape of human brain connectivity.     

Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder

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 potential sparing of local connectivity in ASD. Short-distance U-fibers are an important component of neural networks and are thought to play a crucial role in cognitive function. In the present study, we applied tract-based spatial statistics to derive short- and long-distance white matter tracts in frontal, parietal, and temporal lobes in both hemispheres. DTI data were acquired from 26 children with ASD and 24 typically developing (TD) children. A mean fractional anisotropy (FA) image was created and thinned to represent centers of all common tracts. Evidence of compromised short-distance tracts for the ASD group was found in frontal lobe (reduced FA, increased mean diffusivity [MD] and radial diffusivity) as well as in temporal and parietal lobes (increased MD and radial diffusivity). Significant positive correlations between age and FA and negative correlations between age and MD and radial diffusivity were also found for short-distance tracts in each lobe in the TD, but not the ASD group. These results suggest white matter compromise in short-distance tracts in ASD. Absence of typical age-related correlations with DTI indices may reflect altered maturation of short-distance tracts in ASD. Our results are inconsistent with a notion of selective sparing of short-distance connectivity in ASD.     

Diffusion tensor imaging of white matter and correlates to eye movement control and psychometric testing in children with prenatal alcohol exposure

Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.5 ± 3.2 years) or typically developing control children (n = 67, mean age = 12.1 ± 3.2 years) who underwent brain MRI, eye movement tasks, and psychometric tests. A semi‐automated tractography method extracted fractional anisotropy (FA) and mean diffusivity (MD) values from 15 white matter tracts. The PAE group displayed decreased FA compared with controls in multiple tracts including 3 corpus callosum regions, right corticospinal tract, and 3 left hemisphere tracts connecting to the frontal lobe (cingulum, uncinate fasciculus, and superior longitudinal fasciculus). Significant group by sex interactions were found for the genu, left superior longitudinal fasciculus, and the left uncinate, with females in the PAE group exhibiting lower FA compared with control females. Correlations were found between DTI and eye movement measures in the control group, but these same relationships were absent in the PAE group. In contrast, no correlations were found between DTI and any of the psychometric tests used in this study. These findings support the hypothesis that measures of eye movement control may be valuable functional biomarkers of the brain injury induced by PAE as these tasks reveal group differences that appear to be linked to deficits in white matter integrity in the brain. Hum Brain Mapp 38:444–456, 2017. © 2016 Wiley Periodicals, Inc.     

Alterations of white matter tracts following neurotoxic hippocampal lesions in macaque monkeys: A diffusion tensor imaging study

Diffusion tensor imaging (DTI) is a valuable tool for assessing presumptive white matter alterations in human disease and animal models. The current study used DTI to examine the effects of selective neurotoxic lesions of the hippocampus on major white matter tracts and anatomically related brain regions in macaque monkeys. Two years postlesion, structural MRI, and DTI sequences were acquired for each subject. Volumetric assessment revealed a substantial reduction in the size of the hippocampus in experimental subjects, averaging 72% relative to controls, without apparent damage to adjacent regions. DTI images were processed to yield measures of fractional anisotropy (FA), apparent diffusion coefficient (ADC), parallel diffusivity (lADC), and perpendicular diffusivity (tADC), as well as directional color maps. To evaluate potential changes in major projection systems, a region of interest (ROI) analysis was conducted including the corpus callosum, fornix, temporal stem, cingulum bundle, ventromedial prefrontal white matter, and optic radiations. Lesion‐related abnormalities in the integrity of the fiber tracts examined were limited to known hippocampal circuitry, including the fornix and ventromedial prefrontal white matter. These findings are consistent with the notion that hippocampal damage results in altered interactions with multiple memory‐related brain regions, including portions of the prefrontal cortex. © 2010 Wiley‐Liss, Inc.     

Brain white matter anatomy of tumor patients evaluated with diffusion tensor imaging

We applied multislice, whole-brain diffusion tensor imaging (DTI) to two patients with anaplastic astrocytoma. Data were analyzed using DTI-based, color-coded images and a 3-D tract reconstruction technique for the study of altered white matter anatomy. Each tumor was near two major white matter tracts, namely, the superior longitudinal fasciculus and the corona radiata. Those tracts were identified using the color-coded maps, and spatial relationships with the tumors were characterized. In one patient the tumor displaced adjacent white matter tracts, whereas in the other it infiltrated the superior longitudinal fasciclus without displacement of white matter. DTI provides new information regarding the detailed relationship between tumor growth and nearby white matter tracts, which may be useful for preoperative planning.     

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

White matter microstructure is affected by immune system activity via the actions of circulating pro‐inflammatory cytokines. Although white matter microstructure and inflammatory measures are significantly heritable, it is unclear if overlapping genetic factors influence these traits in humans. We conducted genetic correlation analyses of these traits using randomly ascertained extended pedigrees from the Genetics of Brain Structure and Function Study (N = 1862, 59% females, ages 18–97 years; 42 ± 15.7). White matter microstructure was assessed using fractional anisotropy (FA) calculated from diffusion tensor imaging (DTI). Circulating levels (pg/mL) of pro‐inflammatory cytokines (IL‐6, IL‐8, and TNFα) phenotypically associated with white matter microstructure were quantified from blood serum. All traits were significantly heritable (h² ranging from 0.41 to 0.66 for DTI measures and from 0.18 to 0.30 for inflammatory markers). Phenotypically, higher levels of circulating inflammatory markers were associated with lower FA values across the brain (r = ?.03 to r = ?.17). There were significant negative genetic correlations between most DTI measures and IL‐8 and TNFα, although effects for TNFα were no longer significant when covarying for body mass index. Genetic correlations between DTI measures and IL‐6 were not significant. Understanding the genetic correlation between specific inflammatory markers and DTI measures may help researchers focus questions related to inflammatory processes and brain structure.     

Microstructural abnormalities of white matter differentiate pediatric and adult-onset bipolar disorder

Lu LH, Zhou XJ, Fitzgerald J, Keedy SK, Reilly JL, Passarotti AM, Sweeney JA, Pavuluri M. Microstructural abnormalities of white matter differentiate pediatric and adult onset bipolar disorder. Bipolar Disord 2012: 14: 597–606. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: White‐matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white‐matter deviation may be more pronounced in pediatric than adult‐onset BD. The present study aimed to examine how white‐matter microstructure deviates from a typical maturational trajectory in BD. Methods: Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 9–42) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of the DTI scans. Tract‐based spatial statistics were used to examine the center of white‐matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post‐hoc analyses. Results: The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult‐onset BD. The lower FA in BD was due primarily to greater radial, rather than decreased axial, diffusivity. Conclusions: The ALIC connects the frontal lobes with archistriatum, thalamus, and medial temporal regions, and alteration in these pathways may contribute to mood dysregulation in BD. Abnormalities in this pathway appear to be associated with an earlier onset of illness and thus may reflect a greater susceptibility to illness.     

Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study

A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5-18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full-scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito-parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts.     

磁共振弥散张量成像在脑血管病中的应用

磁共振弥散张量成像（DTI）是一种较新的成像技术,主要用于评估影响脑白质尤其是白质纤维束完整性的疾病,是当前惟一的一种能有效观察和追踪脑白质纤维束的非侵入性检查方法。该技术可定量分析病变组织和正常组织的弥散特征,直观显示颅内病变与白质纤维之间的关系,为诊断疾病和判断预后提供更多的信息。本文就DTI基本原理及其在脑血管病中的临床应用作一概述。     

Diffusion tensor imaging study of white matter fiber tracts in adolescent attention-deficit/hyperactivity disorder

A diffusion tensor imaging (DTI) study was conducted in 12 adolescents with attention deficit/hyperactivity disorder and 14 age- and IQ-matched healthy controls. Inter-subject comparison of fractional anisotropy (FA) of the whole brain between the groups was obtained using the tract-based spatial statistics method. Results revealed significantly lower FA in widespread white matter tracts in cases relative to controls. Also, the FA measure of identified regions was associated with cognitive performance.     

Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation

Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7–14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.     

Evaluation of subcortical white matter and deep white matter tracts in malformations of cortical development

AIMS: Abnormal cortical development will lead to abnormal axons in white matter. The purpose was to investigate (1) the microstructural changes in subcortical white matter adjacent to malformations of cortical development (MCD) and (2) the deep white matter tracts using diffusion tensor imaging (DTI). METHODS: Thirteen children with a variety of MCD were recruited. The fractional anisotropy (FA), trace, and eigenvalues (lambdamajor, lambdamedium, lambdaminor) of subcortical white matter of MCD were compared with contralateral normal side. The deep white matter tracts were graded based on the size, color hues and displacement of the tracts as visualized on color vector maps and tractography; grade 1 was normal tract size and color hue, grade 2 was reduced tract size but preserved color hue and grade 3 was loss of color hue or failure of tracking on tractography. RESULTS: The subcortical white matter adjacent to abnormal cortex demonstrated reduced FA (p < 0.05) and tendency to increase trace (p = 0.06). There was a significant elevation in lambdamedium and lambdaminor (p < 0.05), but no significant change in lambdamajor (p > 0.05). Twelve cases demonstrated alteration in white matter tracts. Seven cases of focal cortical dysplasia and two cases of transmantle MCD demonstrated grade 3 pattern of white matter tract. CONCLUSION: Reduced FA is a sensitive but nonspecific marker of alteration in microstructure of white matter. The elevated lambdamedium and lambdaminor may reflect a dominant effect of abnormal myelin. Alteration in white matter tracts was observed in most cases of MCD.     

White matter microstructural differences linked to left perisylvian language network in children with dyslexia

Studies of dyslexia using diffusion tensor imaging (DTI) have reported fractional anisotropy (FA) differences in left inferior frontal gyrus (LIFG) and left temporo-parietal white matter, suggesting that impaired reading is associated with atypical white matter microstructure in these regions. These anomalies might reflect abnormalities in the left perisylvian language network, long implicated in dyslexia. While DTI investigations frequently report analyses on multiple tensor-derived measures (e.g., FA, orientation, tractography), it is uncommon to integrate analyses to examine the relationships between atypical findings. For the present study, semi-automated techniques were applied to DTI data in an integrated fashion to examine white matter microstructure in 14 children with dyslexia and 17 typically developing readers (ages 7-16 years). Correlations of DTI metrics (FA and fiber orientation) to reading skill (accuracy and speed) and to probabilistic tractography maps of the left perisylvian language tracts were examined. Consistent with previous reports, our findings suggest FA decreases in dyslexia in LIFG and left temporo-parietal white matter. The LIFG FA finding overlaps an area showing differences in fiber orientation in an anterior left perisylvian language pathway. Additionally, a positive correlation of FA to reading speed was found in a posterior circuit previously associated with activation on functional imaging during reading tasks. Overall, integrating results from several complementary semi-automated analyses reveals evidence linking atypical white matter microstructure in dyslexia to atypical fiber orientation in circuits implicated in reading including the left perisylvian language network.     

Anatomical brain connectivity and positive symptoms of schizophrenia: A diffusion tensor imaging study

Structural brain changes in schizophrenia are well documented in the neuroimaging literature. The classical morphometric analyses of magnetic resonance imaging (MRI) data have recently been supplemented by diffusion tensor imaging (DTI), which mainly assesses changes in white matter (WM). DTI increasingly provides evidence for abnormal anatomical connectivity in schizophrenia, most often using fractional anisotropy (FA) as an indicator of the integrity of WM tracts. To better understand the clinical significance of such anatomical changes, we studied FA values in a whole-brain analysis comparing paranoid schizophrenic patients with a history of auditory hallucinations and matched healthy controls. The relationship of WM changes to psychopathology was assessed by correlating FA values with PANSS scores (positive symptoms and severity of auditory hallucinations) and with illness duration. Schizophrenic patients showed FA reductions indicating WM integrity disturbance in the prefrontal regions, external capsule, pyramidal tract, occipitofrontal fasciculus, superior and inferior longitudinal fasciculi, and corpus callosum. The arcuate fasciculus was the only tract which showed increased FA values in patients. Increased FA values in this region correlated with increased severity of auditory hallucinations and length of illness. Our results suggest that local changes in anatomical integrity of WM tracts in schizophrenia may be related to patients' clinical presentation.     

磁共振弥散张量成像在运动功能区星形胶质细胞瘤手术中的运用

目的 探讨磁共振弥散张量成像(DTI)在运动区脑星形胶质细胞瘤恶性程度预测及手术方案制定的临床应用价值.方法 33例运动功能区星形细胞瘤患者,术前进行DTI检查,测量表观弥散系数(ADC值)及各向异性分数(FA值)并重建i维白质纤维束示踪图(DTT图).结果 不同级别星形细胞瘤的肿瘤实质区ADC值及瘤周水肿区FA值存在差异;DTT图可以清楚显示运动区锥体束形态变化及与肿瘤之间的关系,在此基础上指导手术,效果满意.结论 DTI中ADC、FA值可以区别肿瘤组织与正常神经组织,有助于星形细胞瘤分级;DTT图可以优化运动功能区星形细胞瘤切除的手术方案,可最大范围切除肿瘤并有效保护重要白质纤维束.     

Disentangling the relation between left temporoparietal white matter and reading: A spherical deconvolution tractography study

Diffusion tensor imaging (DTI) studies have shown that left temporoparietal white matter is related to phonological aspects of reading. However, DTI lacks the sensitivity to disentangle whether phonological processing is sustained by intrahemispheric connections, interhemispheric connections, or projection tracts. Spherical deconvolution (SD) is a nontensor model which enables a more accurate estimation of multiple fiber directions in crossing fiber regions. Hence, this study is the first to investigate whether the observed relation with reading aspects in left temporoparietal white matter is sustained by a particular pathway by applying a nontensor model. Second, measures of degree of diffusion anisotropy, which indirectly informs about white matter organization, were compared between DTI and SD tractography. In this study, 71 children (5–6 years old) participated. Intrahemispheric, interhemispheric, and projection pathways were delineated using DTI and SD tractography. Anisotropy indices were extracted, that is, fractional anisotropy (FA) in DTI and quantitative hindrance modulated orientational anisotropy (HMOA) in SD. DTI results show that diffusion anisotropy in both the intrahemispheric and projection tracts was positively correlated to phonological awareness; however, the effect was confounded by subjects’ motion. In SD, the relation was restricted to the left intrahemispheric connections. A model comparison suggested that FA was, relatively to HMOA, more confounded by fiber crossings; however, anisotropy indices were highly related. In sum, this study shows the potential of SD to quantify white matter microstructure in regions containing crossing fibers. More specifically, SD analyses show that phonological awareness is sustained by left intrahemispheric connections and not interhemispheric or projection tracts. Hum Brain Mapp 36:3273–3287, 2015. © 2015 Wiley Periodicals, Inc.     

White matter connectivity and aerobic fitness in male adolescents

Exercise has been shown to have positive effects on the brain and behavior throughout various stages of the lifespan. However, little is known about the impact of exercise on neurodevelopment during the adolescent years, particularly with regard to white matter microstructure, as assessed by diffusion tensor imaging (DTI). Both tract-based spatial statistics (TBSS) and tractography-based along-tract statistics were utilized to examine the relationship between white matter microstructure and aerobic exercise in adolescent males, ages 15–18. Furthermore, we examined the data by both (1) grouping individuals based on aerobic fitness self-reports (high fit (HF) vs. low fit (LF)), and (2) using VO₂ peak as a continuous variable across the entire sample. Results showed that HF youth had an overall higher number of streamline counts compared to LF peers, which was driven by group differences in corticospinal tract (CST) and anterior corpus callosum (Fminor). In addition, VO₂ peak was negatively related to FA in the left CST. Together, these results suggest that aerobic fitness relates to white matter connectivity and microstructure in tracts carrying frontal and motor fibers during adolescence. Furthermore, the current study highlights the importance of considering the environmental factor of aerobic exercise when examining adolescent brain development.     

Association of White Matter Integrity With Executive Function and Antidepressant Treatment Outcome in Patients With Late-Life Depression

ObjectiveWhile patients with late-life depression (LLD) often exhibit microstructural white matter alterations that can be identified with diffusion tensor imaging (DTI), there is a dearth of information concerning the links between DTI findings and specific cognitive performance, as well as between DTI measures and antidepressant treatment outcomes.DesignNeuroimaging and cognitive tests were conducted at baseline in 71 older adults participating in a larger, 8-week duration antidepressant randomized controlled trial. Correlations between DTI measures of white matter integrity evaluated with tract-based spatial statistics, baseline neurocognitive performance, and prospective antidepressant treatment outcome were evaluated.ResultsFractional anisotropy (FA), an index of white matter integrity, was significantly positively associated with better cognitive function as measured by the Initiation/Perseveration subscale of the Dementia Rating Scale in the bilateral superior longitudinal fasciculus (SLF), bilateral SLF-temporal, and right corticospinal tract (CST). An exploratory analysis limited to these tracts revealed that increased FA in the right CST, right SLF, and right SLF-temporal tracts was correlated with a greater decrease in depressive symptoms. Increased FA in the right CST predicted a greater chance of remission, while increased FA in the right CST and the right SLF predicted a greater chance of treatment response.ConclusionIn late-life depression LLD subjects, white matter integrity was positively associated with executive function in white matter tracts which act as key connecting structures underlying the cognitive control network. These tracts may play a role as a positive prognostic factor in antidepressant treatment outcome.