Fiber tracking using magnetic resonance diffusion tensor imaging and its applications to human brain development

Diffusion tensor imaging is unique in its ability to noninvasively visualize white matter fiber tracts in the human brain in vivo. Diffusion is the incoherent motion of water molecules on a microscopic scale. This motion is itself dependent on the micro-structural environment that restricts the movement of the water molecules. In white matter fibers there is a pronounced directional dependence on diffusion. With white matter fiber tracking or tractography, projections among brain regions can be detected in the three-dimensional diffusion tensor dataset according to the directionality of the fibers. Examples of developmental changes in diffusion, tracking of major fiber tracts, and examples of how diffusion tensor tractography and functional magnetic resonance imaging can be combined are provided. These techniques are complimentary and allow both the identification of the eloquent areas of the brain involved in specific functional tasks, and the connections between them. The noninvasive nature of magnetic resonance imaging will allow these techniques to be used in both longitudinal developmental and diagnostic studies. An overview of the technique and preliminary applications are presented, along with its current limitations.     

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior–posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application.     

White matter maturation supports the development of reasoning ability through its influence on processing speed

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.     

弥散张量成像在语言认知神经科学研究中的应用

人类的语言功能不仅仅基于以额叶、颞叶为代表的语言脑区灰质皮层的激活, 更重要的是基于这些脑区之间白质纤维束的连接。随着各种脑成像技术的逐渐成熟, 基于核磁共振的弥散张量成像技术在语言认知领域展现出越来越重要的作用。弥散张量成像在语言认知研究上的应用, 可以将其与行为测查、功能定位成像、功能连接、全脑网络等多种分析方法结合来共同研究语言认知, 进而从脑结构的角度来探究语言与脑的关系。     

White matter integrity and pictorial reasoning in high-functioning children with autism

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.     

Neuroimaging Biomarkers in Mild Traumatic Brain Injury (mTBI)

Reviewed herein are contemporary neuroimaging methods that detect abnormalities associated with mild traumatic brain injury (mTBI). Despite advances in demonstrating underlying neuropathology in a subset of individuals who sustain mTBI, considerable disagreement persists in neuropsychology about mTBI outcome and metrics for evaluation. This review outlines a thesis for the select use of sensitive neuroimaging methods as potential biomarkers of brain injury recognizing that the majority of individuals who sustain an mTBI recover without neuroimaging signs or neuropsychological sequelae detected with methods currently applied. Magnetic resonance imaging (MRI) provides several measures that could serve as mTBI biomarkers including the detection of hemosiderin and white matter abnormalities, assessment of white matter integrity derived from diffusion tensor imaging (DTI), and quantitative measures that directly assess neuroanatomy. Improved prediction of neuropsychological outcomes in mTBI may be achieved with the use of targeted neuroimaging markers.     

Monitoring brain development with quantitative diffusion tensor imaging

Quantifying changes that occur during brain maturation may help in diagnosing diseases that affect pediatric patients. By obtaining normative curves that define brain maturation, pathological changes may be easier to recognize. We assessed diffusion changes which are inherently related to the brain structure during maturation and obtained normative curves. MR scans were obtained for 26 pediatric subjects (ages 0 to 11 years) and four adults. The MR images were all normal. Maps of the average diffusion constant (D_av) were calculated for each subject. Changes in D_av were determined with distribution analysis for the entire brain and compared with regions of interest measurements from the periventricular white matter and thalamus. The mean diffusion constant of the whole brain changes quite rapidly as the brain matures. The data suggest that at least two distinct processes are responsible for the change. Quantitative diffusion tensor imaging may provide means of quantifying overall human brain maturation that may be useful in diagnosing pathology.     

Strength of default mode resting-state connectivity relates to white matter integrity in children

A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging. We identified resting-state networks using Independent Component Analysis and tested whether the functional connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) depends upon the maturation of the underlying cingulum white matter tract. To determine the generalizability of this relationship, we also tested whether functional connectivity depends on white matter maturity between bilateral lateral prefrontal cortex (lateral PFC) within the executive control network. We found a positive relationship between mPFC-PCC connectivity and fractional anisotropy of the cingulum bundle; this positive relationship was moderated by the age of the subjects such that it was stronger in older children. By contrast, no such structure-function relationship emerged between right and left lateral PFC. However, functional and structural connectivity of this tract related positively with cognitive speed, fluency, and set-switching neuropsychological measures.     

Mapping the development of white matter tracts with diffusion tensor imaging

In this study, the development of white matter was studied using an optimized diffusion tensor imaging (DTI) protocol in 20 normal subjects (10–40 years old). The normal development of white matter tracts was addressed by comparing the diffusion anisotropy results between two sub‐groups: eight adults (26–38 years old) and eight adolescents (13–15 years old). The difference in myelination extent between these two groups as indexed by the fractional anisotropy was identified by conducting a student t‐test of the measured diffusion anisotropy maps. Significant differences (p < 0.01) were detected in the gyrus frontalis medialis (GFM), gyrus temporalis medialis (GTM) and gyrus cinguli (GC), in addition to the developmental changes in corpus callosum. A brief overview of previous published DTI studies in developmental science and current progress in DTI techniques is also given at the end of this paper. It may be useful for readers interested in using DTI to study developmental problems but who are not familiar with the various technical aspects.     

Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents

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) were evaluated within the splenium and body of the corpus callosum in relation to cognitive performance. Results: Visuospatial construction abilities were associated with white matter integrity in both the splenium and body of the corpus callosum, while only splenium integrity was associated with language and psychomotor function. Conclusion: Results suggest that, for typically developing adolescents, white matter coherence positively relates to visuospatial, psychomotor, and language skills. These findings may have implications for the cognitive functioning of clinical populations in which typical white matter development is altered.     

Sex differences in the IQ-white matter microstructure relationship: A DTI study

Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men.     

Advances in magnetic resonance imaging methods for the evaluation of bipolar disorder

This article reviews the current state of magnetic resonance imaging techniques as applied to bipolar disorder. Addressed are conventional methods of structural neuroimaging and recently developed techniques. This latter group comprises volumetric analysis, voxel-based morphometry, the assessment of T2 white matter hyperintensities, shape analysis, cortical surface-based analysis, and diffusion tensor imaging. Structural analysis methods used in magnetic resonance imaging develop exponentially, and now present opportunities to identify disease-specific neuroanatomic alterations. Greater acuity and complementarity in measuring these alterations has led to the generation of further hypotheses regarding the pathophysiology of bipolar disorder. Included in the summary of findings is consideration of a resulting neuroanatomic model. Integrative issues and future directions in this relatively young field, including multi-modal approaches enabling us to produce more comprehensive results, are discussed.     

Microstructural organization of corpus callosum projections to prefrontal cortex predicts bimanual motor learning

The corpus callosum (CC) is the largest white matter tract in the brain. It enables interhemispheric communication, particularly with respect to bimanual coordination. Here, we use diffusion tensor imaging (DTI) in healthy humans to determine the extent to which structural organization of subregions within the CC would predict how well subjects learn a novel bimanual task. A single DTI scan was taken prior to training. Participants then practiced a bimanual visuomotor task over the course of 2 wk, consisting of multiple coordination patterns. Findings revealed that the predictive power of fractional anisotropy (FA) was a function of CC subregion and practice. That is, FA of the anterior CC, which projects to the prefrontal cortex, predicted bimanual learning rather than the middle CC regions, which connect primary motor cortex. This correlation was specific in that FA correlated significantly with performance of the most difficult frequency ratios tested and not the innately preferred, isochronous frequency ratio. Moreover, the effect was only evident after training and not at initiation of practice. This is the first DTI study in healthy adults which demonstrates that white matter organization of the interhemispheric connections between the prefrontal structures is strongly correlated with motor learning capability.     

Neurocognitive correlates of white matter quality in adolescent substance users

Background

Progressive myelination during adolescence implicates an increased vulnerability to neurotoxic substances and enduring neurocognitive consequences. This study examined the cognitive manifestations of altered white matter microstructure in chronic marijuana and alcohol-using (MJ + ALC) adolescents.

Methods

Thirty-six MJ + ALC adolescents (ages 16–19) and 36 demographically similar controls were evaluated with diffusion tensor imaging (Bava et al., 2009) and neurocognitive tests. Regions of group difference in fractional anisotropy (FA) and mean diffusivity (MD) were analyzed in relation to cognitive performance.

Results

In users, lower FA in temporal areas related to poorer performance on attention, working memory, and speeded processing tasks. Among regions where users had higher FA than controls, occipital FA was positively associated with working memory and complex visuomotor sequencing, whereas FA in anterior regions was negatively associated with verbal memory performance.

Conclusions

Findings suggest differential influences of white matter development on cognition in MJ + ALC using adolescents than in non-using peers. Neuroadaptation may reflect additive and subtractive responses to substance use that are complicated by competing maturational processes.     

Neuroanatomical substrates of age-related cognitive decline

There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and diffusion tensor imaging measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerning measurement and methodology that may lead to stronger conclusions in the future.     

Sex differences in the adolescent brain

Adolescence is a time of increased divergence between males and females in physical characteristics, behavior, and risk for psychopathology. Here we will review data regarding sex differences in brain structure and function during this period of the lifespan. The most consistent sex difference in brain morphometry is the 9–12% larger brain size that has been reported in males. Individual brain regions that have most consistently been reported as different in males and females include the basal ganglia, hippocampus, and amygdala. Diffusion tensor imaging and magnetization transfer imaging studies have also shown sex differences in white matter development during adolescence. Functional imaging studies have shown different patterns of activation without differences in performance, suggesting male and female brains may use slightly different strategies for achieving similar cognitive abilities. Longitudinal studies have shown sex differences in the trajectory of brain development, with females reaching peak values of brain volumes earlier than males. Although compelling, these sex differences are present as group averages and should not be taken as indicative of relative capacities of males or females.     

Transverse diffusivity of cerebral parenchyma predicts visual tracking performance in relapsing–remitting multiple sclerosis

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing–remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined in the cerebral parenchyma. Cognitive performance of the MS patients was assessed with the oral response format of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). A significant correlation was found between performance on the SDMT and the fractional anisotropy in the brain. This correlation was predominantly induced by transverse diffusivity. Transverse diffusivity refers to the diffusion across fibers rather than along the fibers and is believed to be a specific marker for axonal loss and demyelination associated with MS. No significant association between DTI-measures and PASAT performance was found and this negative finding was mainly attributed to psychometric qualities. These results indicate that diffusivity along the non-principal diffusion direction, a possible signature of MS-related white matter pathology, contributes to information processing speed as measured with the SDMT, a task that requires close visual tracking and a widely used clinical marker for cognitive decline in MS.     

DEVELOPMENTAL SEX DIFFERENCES IN THE RELATION OF NEUROANATOMICAL CONNECTIVITY TO INTELLIGENCE

Recent neuroimaging research has shown sex-related differences in the relationship between brain structure and cognitive function. Anatomical studies have shown a greater reliance for cognitive function on white matter structure in adult females, and a greater reliance on gray matter structure in adult males. Functional neuroimaging studies have also shown a greater correlation between brain connectivity and cognitive function in females. However, this relationship is not present in young childhood (5 years old) but appears during the developmental period. Here sex differences in structure–function relationships and their developmental trajectory are investigated using diffusion tensor imaging (DTI) on a large cohort of over 100 normal children ages 5–18. Significant sex–X–IQ interactions on fractional anisotropy (FA), a marker for white matter organization, were seen in the left frontal lobe, in fronto-parietal areas bilaterally, and in the arcuate fasciculus bilaterally, with girls showing positive correlations of FA with IQ, and boys showing a negative correlation. Significant sex–X–IQ–X–age interactions on FA were also seen in the left frontal lobe and in fronto-parietal areas bilaterally, showing a developmental effect. These results strongly corroborate previous findings regarding sex differences in structure–function relationships regarding intelligence. Results also indicate that a naïve interpretation of “more is better” with respect to FA may not be accurate, especially in adult males.     

长期高策略性技能训练对运动员大脑白质结构的影响：一项DTI研究

目前关于运动员经验优势的脑机制还存在争议, 尤其对于涉及较多认知过程参与的高策略性技能项目运动员, 其大脑白质结构可塑性变化还需进一步探究。研究横向对比了乒乓球运动员和非运动员大脑白质纤维束的弥散张量成像数据。结果发现, 相比于非运动员, 乒乓球运动员在连接背侧和腹侧通路脑区的双侧皮质脊髓束、左侧上纵束、左侧下纵束和双侧额枕下束的各向异性值(FA)更大, 进一步分析发现, 部分腹侧通路白质纤维束FA增加的原因是径向扩散系数(RD)下降。研究结果支持了动作双通路模型。提示经过长期高策略性技能训练, 乒乓球运动员在背侧和腹侧通路上的白质纤维束结构完整性增强。     

扩散张量成像在脑胶质瘤诊治中的应用

扩散张量成像是目前唯一可以在活体显示大脑内白质纤维走向的磁共振成像技术,对于脑胶质瘤术前诊断,制定手术计划,指导手术及判定预后等方面是非常有帮助的。综述了近年来扩散张量成像技术在脑胶质瘤诊断、治疗及判定预后中的应用价值,并结合文献提出了目前存在的不足。