A multiple streamline approach to high angular resolution diffusion tractography

Diffusion-weighted magnetic resonance imaging has the ability to map neuronal architecture by estimating the 3D diffusion displacement within fibrous brain structures. This approach has non-invasively been demonstrated in the human brain with diffusion tensor tractography. Despite its valuable application in neuroscience and clinical studies however, it faces an inherent limit in mapping fiber tracts through areas with intervoxel incoherence. Recent advances in high angular resolution diffusion imaging have surpassed this limit and have the ability to resolve the complex fiber intercrossing within each MR voxel. To connect the fiber tracts from a multi-fiber system, this study proposed a modified fiber assignment using the continuous tracking (MFACT) algorithm and a tracking browser to propagate tracts along complex diffusion profiles. The Q-ball imaging method was adopted to acquire the diffusion displacements. Human motor pathways with seed points from the internal capsule, motor cortex, and pons were studied respectively. The results were consistent with known anatomy and demonstrated the promising potential of the MFACT method in mapping the complex neuronal architecture in the human brain.     

Diffusion tensor imaging reveals evolution of primate brain architectures

Evolution of the brain has been an inherently interesting problem for centuries. Recent studies have indicated that neuroimaging is a powerful technique for studying brain evolution. In particular, a variety of reports have demonstrated that consistent white matter fiber connection patterns derived from diffusion tensor imaging (DTI) tractography reveal common brain architecture and are predictive of brain functions. In this paper, based on our recently discovered 358 dense individualized and common connectivity-based cortical landmarks (DICCCOL) defined by consistent fiber connection patterns in DTI datasets of human brains, we derived 65 DICCCOLs that are common in macaque monkey, chimpanzee and human brains and 175 DICCCOLs that exhibit significant discrepancies amongst these three primate species. Qualitative and quantitative evaluations not only demonstrated the consistencies of anatomical locations and structural fiber connection patterns of these 65 common DICCCOLs across three primates, suggesting an evolutionarily preserved common brain architecture but also revealed regional patterns of evolutionarily induced complexity and variability of those 175 discrepant DICCCOLs across the three species.     

Tracing superior longitudinal fasciculus connectivity in the human brain using high resolution diffusion tensor tractography

The major language pathways such as superior longitudinal fasciculus (SLF) pathways have been outlined by experimental and diffusion tensor imaging (DTI) studies. The SLF I and some of the superior parietal lobule connections of the SLF pathways have not been depicted by prior DTI studies due to the lack of imaging sensitivity and adequate spatial resolution. In the current study, the trajectory of the SLF fibers has been delineated on five healthy human subjects using diffusion tensor tractography on a 3.0-T scanner at high spatial resolution. We also demonstrate for the first time the trajectory and connectivity of the SLF fibers in relation to other language pathways as well as the superior parietal lobule connections of the language circuit using high spatial resolution DTI in the healthy adult human brain.     

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.     

Mapping brain anatomical connectivity using white matter tractography

Integration of the neural processes in the human brain is realized through interconnections that exist between different neural centers. These interconnections take place through white matter pathways. White matter tractography is currently the only available technique for the reconstruction of the anatomical connectivity in the human brain noninvasively and in vivo. The trajectory and terminations of white matter pathways are estimated from local orientations of nerve bundles. These orientations are obtained using measurements of water diffusion in the brain. In this article, the techniques for estimating fiber directions from diffusion measurements in the human brain are reviewed. Methods of white matter tractography are described, together with the current limitations of the technique, including sensitivity to image noise and partial voluming. The applications of white matter tractography to the topographical characterization of the white matter connections and the segmentation of specific white matter pathways, and corresponding functional units of gray matter, are discussed. In this context, the potential impact of white matter tractography in mapping the functional systems and subsystems in the human brain, and their interrelations, is described. Finally, the applications of white matter tractography to the study of brain disorders, including fiber tract localization in brains affected by tumors and the identification of impaired connectivity routes in neurologic and neuropsychiatric diseases, are discussed.     

应用DTI技术对人脑白质纤维束的初步研究

目的建立扩散张量纤维束成像对人脑白质纤维的显示方法,并应用中国数字化可视人体数据进行对照观察,验证扩散张量成像(DTI)方法的可靠性。方法选择5名健康志愿者进行DTI成像,采用DtiStudio软件进行分析处理,重建出部分各向异性(FA)图、容积比(VR)图、相对各向异性(RA)图、表面扩散系数(ADC)图以及二维彩色张量图。应用中国数字化可视人体数据集断面图像、FA图及彩色FA图进行对照观察,利用fibertracking纤维跟踪软件及3DMRI软件进行三维重建显示脑内主要白质纤维束,辨认脑内白质纤维束的位置、形态。结果应用DTI纤维束成像可以清晰准确地描绘脑白质内主要神经纤维束的解剖图谱,包括联络纤维如弓形纤维、钩束、扣带束、上纵束和下纵束,连合纤维如胼胝体、前连合和穹隆,投射纤维如锥体束、视放射、内侧丘系等。DTI纤维束成像结果与已知解剖知识、中国可视化人体断面图像具有很好的一致性。结论应用DTI纤维束成像可以清晰准确地描绘脑白质内主要神经纤维束的解剖图谱,其结果与中国可视化人体断面图像、已知解剖知识是一致的,应用DTI纤维束成像研究脑内纤维连通性是可靠的。     

纤维跟踪技术在模拟显示人脑联络纤维中的应用

目的：应用弥散张量（DTI）纤维跟踪技术来模拟显示脑的联络纤维，探讨结果与经典解剖学知识的一致性。方法：对1个志愿者行单次激发回波平面弥散张量成像，利用纤维跟踪技术来模拟显示其联络纤维，并观察与经典解剖学知识的一致性。结果：通过选择恰当的感兴趣区，各向异性阈值、角度阈值、步长和体素内采样数目等参数，利用弥散张量纤维跟踪技术可模拟显示扣带、上枕额束、下枕额束、钩束、下纵束等联络纤维。结论：利用弥散张量纤维跟踪技术可模拟显示人脑联络纤维，且与经典解剖学有高度一致性，是在活体中研究人脑联络纤维的一种新方法。     

Reduced structural connectivity in Insomnia Disorder

Insomnia Disorder is the most prevalent sleep disorder, and it involves both sleep difficulties and daytime complaints. The neural underpinnings of Insomnia Disorder are poorly understood. Several existing neuroimaging studies focused on local measures and specific regions of interests, which makes it difficult to judge their whole‐brain significance. We therefore here applied a data‐driven approach to assess differences in whole‐brain structural connectivity between adults with Insomnia Disorder and matched controls without sleep complaints. We used diffusion tensor imaging and probabilistic tractography to assess whole‐brain structural connectivity, and examined group differences using network‐based statistics. The results revealed a significant difference in the structural connectivity of the two groups (p = .014). Participants with Insomnia Disorder showed reduced connectivity in a sub‐network that included mainly fronto‐subcortical connections with the insula as a key region. By taking a whole‐brain network perspective, our study enables the integration of previous inconsistent findings. Our results reveal that reduced structural connectivity of the left insula and the connections between frontal and subcortical regions are central neurobiological features of Insomnia Disorder. The importance of these areas for interoception, emotional processing, stress responses and the generation of slow‐wave sleep may help guide the development of neurobiology‐based models of the prevalent condition of Insomnia Disorder.     

Diffusion MRI fiber tractography of the brain

The ability of fiber tractography to delineate non‐invasively the white matter fiber pathways of the brain raises possibilities for clinical applications and offers enormous potential for neuroscience. In the last decade, fiber tracking has become the method of choice to investigate quantitative MRI parameters in specific bundles of white matter. For neurosurgeons, it is quickly becoming an invaluable tool for the planning of surgery, allowing for visualization and localization of important white matter pathways before and even during surgery. Fiber tracking has also claimed a central role in the field of “connectomics,” a technique that builds and studies comprehensive maps of the complex network of connections within the brain, and to which significant resources have been allocated worldwide. Despite its unique abilities and exciting applications, fiber tracking is not without controversy, in particular when it comes to its interpretation. As neuroscientists are eager to study the brain's connectivity, the quantification of tractography‐derived “connection strengths” between distant brain regions is becoming increasingly popular. However, this practice is often frowned upon by fiber‐tracking experts. In light of this controversy, this paper provides an overview of the key concepts of tractography, the technical considerations at play, and the different types of tractography algorithm, as well as the common misconceptions and mistakes that surround them. We also highlight the ongoing challenges related to fiber tracking. While recent methodological developments have vastly increased the biological accuracy of fiber tractograms, one should be aware that, even with state‐of‐the‐art techniques, many issues that severely bias the resulting structural “connectomes” remain unresolved.     

Mapping of the mouse olfactory system with manganese-enhanced magnetic resonance imaging and diffusion tensor imaging

As the power of studying mouse genetics and behavior advances, research tools to examine systems level connectivity in the mouse are critically needed. In this study, we compared statistical mapping of the olfactory system in adult mice using manganese-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) with probabilistic tractography. The primary goal was to determine whether these complementary techniques can determine mouse olfactory bulb (OB) connectivity consistent with known anatomical connections. For MEMRI, 3D T1-weighted images were acquired before and after bilateral nasal administration of MnCl₂ solution. Concomitantly, high-resolution diffusion-tensor images were obtained ex vivo from a second group of mice and processed with a probabilistic tractography algorithm originating in the OB. Incidence maps were created by co-registering and overlaying data from the two scan modalities. The resulting maps clearly show pathways between the OB and amygdala, piriform cortex, caudate putamen, and olfactory cortex in both the DTI and MEMRI techniques that are consistent with the known anatomical connections. These data demonstrate that MEMRI and DTI are complementary, high-resolution neuroimaging tools that can be applied to mouse genetic models of olfactory and limbic system connectivity.     

Structural correlates of the orbitofrontal cortex and amygdala and personality in female adolescents

The five‐factor model consists of cognitive‐affective‐behavioral trait dimensions (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness) that are central to models of psychopathology. In adults, individual differences in three of the Big Five traits, neuroticism, extraversion, and conscientiousness, have been linked to structural morphology and connectivity of the orbitofrontal cortex (OFC) and the amygdala, two brain regions critically involved in affective and regulatory processing. It is unclear whether these associations manifest in adolescence, a critical neurodevelopmental period during which many forms of psychiatric illness emerge. A total of 223 adolescent girls (ages 14–16 years) completed a multimodal neuroimaging study that utilized T1‐weighted structural MRI (e.g., cortical thickness and volume) and tractography‐based diffusion tensor imaging (64‐direction). Cortical thickness and volume were extracted from the medial orbitofrontal cortex (mOFC) and amygdala and tractography‐based fractional anisotropy was computed in the uncinate fasciculus (UF; the white matter tract connecting the OFC to the temporal lobe). We found that high neuroticism was associated with less mOFC volume (bilateral), and low conscientiousness was associated with higher white matter integrity in the UF, more amygdala volume, and less mOFC thickness (right hemisphere). Extraversion was not observed to share associations with OFC markers. These OFC‐amygdala structural correlations to personality do not match those reported in adult samples. Multimodal neuroimaging techniques can help to clarify the underpinnings of personality development between adolescence and adulthood.     

Semi-automated 3D segmentation of major tracts in the rat brain: comparing DTI with standard histological methods

Researchers working with rodent models of neurological disease often require an accurate map of the anatomical organization of the white matter of the rodent brain. With the increasing popularity of small animal MRI techniques, including diffusion tensor imaging (DTI), there is considerable interest in rapid segmentation methods of neurological structures for quantitative comparisons. DTI-derived tractography allows simple and rapid segmentation of major white matter tracts, but the anatomic accuracy of these computer-generated fibers is open to question and has not been rigorously evaluated in the rat brain. In this study, we examine the anatomic accuracy of tractography-based segmentation in the adult rat brain. We analysed 12 major white matter pathways using semi-automated tractography-based segmentation alongside manual segmentation of Gallyas silver-stained histology sections. We applied four fiber-tracking algorithms to the DTI data—two integration methods and two deflection methods. In many cases, tractography-based segmentation closely matched histology-based segmentation; however different tractography algorithms produced dramatically different results. Results suggest that certain white matter pathways are more amenable to tractography-based segmentation than others. We believe that these data will help researchers decide whether it is appropriate to use tractography-based segmentation of white matter structures for quantitative DTI-based analysis of neurologic disease models.     

Subcortical anatomy of the lateral association fascicles of the brain: A review

Precise knowledge of the connectivities of the different white matter bundles is of great value for neuroscience research. Our knowledge of subcortical anatomy has improved exponentially during recent decades owing to the development of magnetic resonance diffusion tensor imaging tractography (DTI). Although DTI tractography has led to important progress in understanding white matter anatomy, the precise trajectory and cortical connections of the subcortical bundles remain poorly determined. The recent literature was extensively reviewed in order to analyze the trajectories and cortical terminations of the lateral association fibers of the brain.The anatomy of the following tracts is reviewed: superior longitudinal fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto‐occipital fasciculus, uncinate fasciculus, frontal aslant tract, and vertical occipital fasciculus. The functional role of a tract can be inferred from its topography within the brain. Knowing the functional roles of the cortical areas connected by a certain bundle, it is possible to develop new insights into the putative functional properties of such connections. Clin. Anat. 563–569, 2014. © 2014 Wiley Periodicals, Inc.     

Brain morphological analysis in PTEN hamartoma tumor syndrome

PTEN hamartoma tumor syndrome (PHTS) is a spectrum of hereditary cancer syndromes caused by germline mutations in PTEN. PHTS is of high interest, because of its high rate of neurological comorbidities including macrocephaly, autism spectrum disorder, and intellectual dysfunction. Since detailed brain morphology and connectivity of PHTS remain unclear, we quantitatively evaluated brain magnetic resonance imaging (MRI) in PHTS. Sixteen structural T1‐weighted and 9 diffusion‐weighted MR images from 12 PHTS patients and neurotypical controls were used for structural and high‐angular resolution diffusion MRI (HARDI) tractography analyses. Mega‐corpus callosum was observed in 75%, polymicrogyria in 33%, periventricular white matter lesions in 83%, and heterotopia in 17% of the PHTS participants. While gyrification index and hemispheric cortical thickness showed no significant differences between the two groups, significantly increased global and regional brain volumes, and regionally thicker cortices in PHTS participants were observed. HARDI tractography showed increased volume and length of callosal pathways, increased volume of the arcuate fasciculi (AF), and increased length of the bilateral inferior longitudinal fasciculi (ILF), bilateral inferior fronto‐occipital fasciculi (IFOF), and bilateral uncinate fasciculus. A decrease in fractional anisotropy and an increased in apparent diffusion coefficient values of the AF, left ILF, and left IFOF in PHTS.     

Leading non‐Gaussian corrections for diffusion orientation distribution function

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. Copyright © 2013 John Wiley & Sons, Ltd.     

Functional anatomy of interhemispheric cortical connections in the human brain

Interhemsipheric interaction between the human cerebral hemispheres is served by abundant white-matter fibres in the human corpus callosum (CC). Damage to these fibres has notable behavioural and cognitive sequelae that depend on the exact location of the fibre loss. Until now, correlations between fibre loss and neurological disorders have been limited to post-mortem studies. Here we used probabilistic diffusion magnetic resonance imaging tractography to produce a two-dimensional map of the CC in the mid-sagittal plane. We observed an antero-posterior topography of interhemispheric tracts within the CC, consistent with our current neuroanatomical understanding of post-mortem studies in human. Callosal tract to the left and right hemispheres had comparable volume. Gender, a factor that is often reported to affect CC shape and geometry, also had no effect on the volume of the tracts. Our map showed high consistency across individuals. We propose that this map might be useful in the study of the effects of damage to human CC in neurodegenerative and cognitive disorders.     

Diffusion tensor imaging shows white matter tracts between human auditory and visual cortex

Although it is known that sounds can affect visual perception, the neural correlates for crossmodal interactions are still disputed. Previous tracer studies in non-human primates revealed direct anatomical connections between auditory and visual brain areas. We examined the structural connectivity of the auditory cortex in normal humans by diffusion-weighted tensor magnetic resonance imaging and probabilistic tractography. Tracts were seeded in Heschl's region or the planum temporale. Fibres crossed hemispheres at the posterior corpus callosum. Ipsilateral fibres seeded in Heschl's region projected to the superior temporal sulcus, the supramarginal gyrus and intraparietal sulcus and the occipital cortex including the calcarine sulcus. Fibres seeded in the planum temporale terminated primarily in the superior temporal sulcus, the supramarginal gyrus, the central sulcus and adjacent regions. Our findings suggest the existence of direct white matter connections between auditory and visual cortex--in addition to subcortical, temporal and parietal connections.     

Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia

Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity.     

Assessing neuronal networks: Understanding Alzheimer's disease

Findings derived from neuroimaging of the structural and functional organization of the human brain have led to the widely supported hypothesis that neuronal networks of temporally coordinated brain activity across different regional brain structures underpin cognitive function. Failure of integration within a network leads to cognitive dysfunction. The current discussion on Alzheimer's disease (AD) argues that it presents in part a disconnection syndrome. Studies using functional magnetic resonance imaging, positron emission tomography and electroencephalography demonstrate that synchronicity of brain activity is altered in AD and correlates with cognitive deficits. Moreover, recent advances in diffusion tensor imaging have made it possible to track axonal projections across the brain, revealing substantial regional impairment in fiber-tract integrity in AD. Accumulating evidence points towards a network breakdown reflecting disconnection at both the structural and functional system level. The exact relationship among these multiple mechanistic variables and their contribution to cognitive alterations and ultimately decline is yet unknown. Focused research efforts aimed at the integration of both function and structure hold great promise not only in improving our understanding of cognition but also of its characteristic progressive metamorphosis in complex chronic neurodegenerative disorders such as AD.     

Developmental imaging genetics: challenges and promises for translational research

Advances in molecular biology, neuroimaging, genetic epidemiology, and developmental psychopathology have provided a unique opportunity to explore the interplay of genes, brain, and behavior within a translational research framework. Herein, we begin by outlining an experimental strategy by which genetic effects on brain function can be explored using neuroimaging, namely, imaging genetics. We next describe some major findings in imaging genetics to highlight the effectiveness of this strategy for delineating biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. We then discuss the importance of applying imaging genetics to the study of psychopathology within a developmental framework. By beginning to move toward a systems-level approach to understanding pathways to behavioral outcomes as they are expressed across development, it is anticipated that we will move closer to understanding the complexities of the specific mechanisms involved in the etiology of psychiatric disease. Despite the numerous challenges that lie ahead, we believe that developmental imaging genetics has potential to yield highly informative results that will ultimately translate into public health benefits. We attempt to set out guidelines and provide exemplars that may help in designing fruitful translational research applications that incorporate a developmental imaging genetics strategy.