Independent component analysis of DTI reveals multivariate microstructural correlations of white matter in the human brain

It has recently been demonstrated that specific patterns of correlation exist in diffusion tensor imaging (DTI) parameters across white matter tracts in the normal human brain. These microstructural correlations are thought to reflect phylogenetic and functional similarities between different axonal fiber pathways. However, this earlier work was limited in three major respects: (1) the analysis was restricted to only a dozen selected tracts; (2) the DTI measurements were averaged across whole tracts, whereas metrics such as fractional anisotropy (FA) are known to vary considerably within single tracts; and (3) a univariate measure of correlation was used. In this investigation, we perform an automated multivariate whole-brain voxel-based study of white matter FA correlations using independent component analysis (ICA) of tract-based spatial statistics computed from 3T DTI in 53 healthy adult volunteers. The resulting spatial maps of the independent components show voxels for which the FA values within each map co-vary across individuals. The strongest FA correlations were found in anatomically recognizable tracts and tract segments, either singly or in homologous pairs. Hence, ICA of DTI provides an automated unsupervised decomposition of the normal human brain into multiple separable microstructurally correlated white matter regions, many of which correspond to anatomically familiar classes of white matter pathways. Further research is needed to determine whether whole-brain ICA of DTI represents a novel alternative to tractography for feature extraction in studying the normal microstructure of human white matter as well as the abnormal white matter microstructure found in neurological and psychiatric disorders.     

Age-related deficits in fronto-temporal connections in schizophrenia: a diffusion tensor imaging study

OBJECTIVE: Impairment of white matter connecting frontal and temporal cortices has been reported in schizophrenia. Yet, not much is known about the effects of age on fibers connecting these brain regions. Using diffusion tensor imaging tractography, we investigated the relationship between age and fiber integrity in patients with schizophrenia vs. healthy adults. METHODS: DTI tractography was used to create 3D reconstructions of the cingulum, uncinate and inferior occipito-frontal fasciculi in 27 patients with schizophrenia and 34 healthy volunteers (23-56 years of age, group-matched on age). Fractional anisotropy (FA), describing fiber integrity, was then calculated along the entire length of these tracts, and correlated with subjects' age. RESULTS: Patients revealed a significant decline in FA with age in both the cingulum and uncinate, but not in the inferior occipito-frontal fasciculi. No statistically significant correlations were found in these fiber bundles in controls. CONCLUSIONS: These results suggest an age-associated reduction of frontal-temporal connectivity in schizophrenia, but not in healthy controls.     

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

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

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.     

Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. METHODS: DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. RESULTS: Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. CONCLUSIONS: This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.     

Altered white matter connectivity in never‐medicated patients with schizophrenia

Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication‐naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract‐based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group‐related differences as disease‐related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. Hum Brain Mapp 34:2353–2365, 2013. © 2012 Wiley Periodicals, Inc.     

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 and fiber tractography in acute stroke

Diffusion tensor imaging (DTI) permits the quantitative evaluation of white matter pathology using measures of diffusion anisotropy. Fiber tractography based on DTI can reveal the three-dimensional white matter connectivity of the human brain. DTI fiber tractography is used to localize stroke lesions in relation to functionally important pathways and to assess wallerian degeneration, which may allow more accurate prognosis of long-term recovery or disability. DTI also improves the evaluation of hypoxic-ischemic injury to the developing brain of newborns and infants. DTI and fiber tractography may prove useful in elucidating alterations in brain connectivity resulting from neuroplasticity after stroke.     

Construction of a stereotaxic DTI atlas with full diffusion tensor information for studying white matter maturation from childhood to adolescence using tractography‐based segmentations

Reconstruction of white matter (WM) fiber tracts based on diffusion tensor imaging (DTI) is increasingly being used in clinical and research settings to study normal and pathological WM tissue as well as the maturation of this WM tissue. Such fiber tracking (FT) methodology, however, is highly dependent on the manual delineation of anatomical landmarks and the algorithm settings, often rendering the reproducibility and reliability questionable. Predefining these regions of interest on a fractional anisotropy (FA) atlas in standard space has already been shown to improve the reliability of FT results. In this paper, we constructed a new DTI atlas, which contains the complete diffusion tensor information in ICBM152 coordinates. From this high‐dimensional DTI atlas, and using robust FT protocols, we reconstructed a large number of WM tracts. Subsequently, we created tract masks from these fiber tract bundles and evaluated the atlas framework by comparing the reproducibility of the results obtained from our standardized tract masks with regions‐of‐interest labels from the conventional FA‐based WM atlas. Finally, we assessed laterality and age‐related WM changes in 42 normal subjects aged 0 to 18 years using these tractography‐derived tract segmentations. In agreement with previous literature, we observed an FA increase with age, which was mainly due to the decrease of perpendicular diffusivity. In addition, major functional pathways in the language, motor, and limbic system, showed a significant asymmetry in terms of the observed diffusion metrics. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

White matter fiber tractography and color mapping of the normal human cerebellum with diffusion tensor imaging

Diffusion tensor imaging (DTI) color mapping and fiber tractography was used to study the white matter within the cerebellum along with the afferent and efferent tracts associated with the cerebellum in 24 normal human subjects. The most prominent structures that can be readily identified using these DTI techniques are the middle, inferior and superior cerebellar peduncles. Furthermore DTI shows transverse white matter fiber that cross between the two cerebellar hemispheres at the level of the vermis. At the hemispheric level fibers to the dentate, to the emboliform nuclei are clearly visible on DTI as is the afferent pathway represented by the middle cerebellar peduncle. Selective DTI fiber tractography provides very exquisite images of the cerebellar peduncles and of the fibers projecting to and from the cerebellar cortex. This study demonstrates that DTI is complementary to conventional MRI in that DTI elucidates the orientation of white matter fiber bundles that are associated with the cerebellum. Therefore we anticipate that DTI will become an important adjunct to conventional MRI for clinical and basic studies of cerebellar ataxias and congenital disorders involving the cerebellum and brain stem. This work provides a summary of the normal DTI appearance of the cerebellar white matter which will be useful for interpreting DTI results in clinical populations.     

Diffusion tensor imaging: Application to the study of the developing brain

OBJECTIVE: To provide an overview of diffusion tensor imaging (DTI) and its application to the study of white matter in the developing brain in both healthy and clinical samples. METHOD: The development of DTI and its application to brain imaging of white matter tracts is discussed. Forty-eight studies using DTI to examine diffusion properties of the developing brain are reviewed in the context of the structural magnetic resonance imaging literature. Reports of how brain diffusion properties are affected in pediatric clinical samples and how they relate to cognitive and behavioral phenotypes are reviewed. RESULTS: DTI has been used successfully to describe white matter development in pediatric samples. Changes in white matter diffusion properties are consistent across studies, with anisotropy increasing and overall diffusion decreasing with age. Diffusion measures in relevant white matter regions correlate with behavioral measures in healthy children and in clinical pediatric samples. CONCLUSIONS: DTI is an important tool for providing a more detailed picture of developing white matter than can be obtained with conventional magnetic resonance imaging alone.     

Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging

Using magnetic resonance diffusion tensor imaging (DTI), the present study investigates changes in both gray and white matter in the APPsw transgenic mouse (Tg2576), a model of beta-amyloid plaque deposition associated with Alzheimer's disease (AD). DTI analyses were performed in cross-sectional groups of transgene-positive and -negative mice at 8, 12, 16, and 18 months of age to assess the magnitude of water diffusion in gray matter (i.e., Tr(D)) and changes in diffusion in white matter that may be indicative of axonal degeneration (i.e., reduced water diffusion parallel to axonal tracts, lambda(||)) and myelin degradation (i.e., increased water diffusion perpendicular to axonal tracts, lambda(perpendicular)). No appreciable changes in gray or white matter were observed between the APPsw and the age-matched control mice at 8 months of age. Reduced Tr(D) and lambda(||) were observed in gray and white matter, respectively, for the APPsw mice at ages greater than 8 months, which coincides with the time period when appreciable amyloid plaque accumulation was confirmed by ex vivo histopathological studies. The decreases in lambda(||) suggest the presence of axonal injury in multiple white matter tracts of APPsw mice. Unlike lambda(||), lambda(perpendicular) was unaltered between control and APPsw mice in most white matter tracts. However, in the corpus collosum (CC), lambda(perpendicular) increased at 16 and 18 months of age, suggesting the possibility of myelin damage in the CC at these later ages. This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues.     

Undecussated Superior Cerebellar Peduncles and Absence of the Dorsal Transverse Pontine Fibers: a New Axonal Guidance Disorder?

Axonal guidance disorders are a newly recognized group of diseases of the human central nervous system. These disorders are characterized by white matter tracts with abnormal course and failure to cross the midline or presence of ectopic white matter tracts. Diffusion tensor imaging (DTI) and fiber tractography are suitable neuroimaging tools to detect morphological abnormalities in the course, decussation, and location of white matter tracts. We report on a 6.5-year-old child with significant global developmental delay. Axial color-coded fractional anisotropy (FA)-maps revealed absence of (1) the midline “focal red dot” at the level of the pontomesencephalic junction representing absence of decussation of the superior cerebellar peduncles and (2) the dorsal component of the transverse pontine fibers. These findings are highly suggestive of an axonal guidance disorders. The complete neuroimaging phenotype of this child does not match well-known diseases with similar DTI findings. We show how DTI reveals important information of microstructural brain malformations that may go undetected or remains underestimated and consequently DTI may suggest the possible pathomechanism. We conclude that this child may be suffering from a not yet described subtype of an axonal guidance disorder.     

Autism as a disconnection syndrome: A qualitative and quantitative review of diffusion tensor imaging studies

This review aims at evaluating the leading hypothesis of lower long-range and greater short-range cortical connectivity in individuals with autism spectrum disorder (ASD) by the available literature on diffusion tensor imaging (DTI) studies. DTI, coupled with tractography, assesses the structural connections between cortical regions and quantifies their white matter integrity. First, we provide an extensive qualitative overview of DTI findings in ASD. Next, to reveal convergence between studies, results are quantitatively analyzed using Activation Likelihood Estimation (ALE) and fibre tracking is performed to visualize the white matter tracts running through the obtained ALE clusters. Finally, findings from DTI research are related to specific symptoms characteristic of ASD. Overall, the qualitative analysis yields a widespread disruption of white matter integrity in the brain of individuals with ASD as compared to typically developing controls. This is the case for both the long-range and the local short-range connections, partially contradicting the leading hypothesis. However, several studies investigating very young children with ASD report greater structural connectivity, suggesting a developmental switch in white matter integrity in the ASD brain. Based on the combined qualitative and quantitative analysis, the corpus callosum and the ventral tracts emerge as particularly affected connections in individuals with ASD.     

Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.     

精神发育迟滞脑白质磁共振弥散张量成像研究

目的:通过检查精神发育迟滞(MR)患者脑白质磁共振弥散张量成像(DTI)来了解该病患者脑白质发育情况,以寻找MR患者新的诊断手段,并探讨发病机制中脑白质纤维束发育障碍的根据.方法:用DTI扫描技术对45例MR患者作了皮质脊髓束、枕额束、扣带束、胼胝体束的检查.结果:45例患者中仅4例未发现异常,枕额束有异常为27例,皮...     

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.     

Compromised Neurocircuitry in Chronic Blast‐Related Mild Traumatic Brain Injury

The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI‐based deterministic and probabilistic tractography to access local and global diffusion changes in blast‐induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post‐concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison. DTI results were examined in relation to post‐concussion and post‐traumatic stress disorder (PTSD) symptoms. No significant group difference in DTI metrics was found using voxel‐wise analysis. However, group comparison using tract profile analysis and tract specific analysis, as well as single subject analysis using tract profile analysis revealed the most prominent white matter microstructural injury in chronic bmTBI patients over the frontal fiber tracts, that is, the front‐limbic projection fibers (cingulum bundle, uncinate fasciculus), the fronto‐parieto‐temporal association fibers (superior longitudinal fasciculus), and the fronto‐striatal pathways (anterior thalamic radiation). Effects were noted to be sensitive to the number of previous blast exposures, with a negative association between fractional anisotropy (FA) and time since most severe blast exposure in a subset of the multiple blast‐exposed group. However, these patterns were not observed in the subgroups classified using macrostructural changes (T2 white matter hyperintensities). Moreover, post‐concussion symptoms and PTSD symptoms, as well as neuropsychological function were associated with low FA in the major nodes of compromised neurocircuitry. Hum Brain Mapp 38:352–369, 2017. © 2016 Wiley Periodicals, Inc.     

A review of diffusion tensor imaging studies in schizophrenia

Both post-mortem and neuroimaging studies have contributed significantly to what we know about the brain and schizophrenia. MRI studies of volumetric reduction in several brain regions in schizophrenia have confirmed early speculations that the brain is disordered in schizophrenia. There is also a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in this disorder. Thus an interest in white matter fiber tracts, subserving anatomical connections between distant, as well as proximal, brain regions, is emerging. This interest coincides with the recent advent of diffusion tensor imaging (DTI), which makes it possible to evaluate the organization and coherence of white matter fiber tracts. This is an important advance as conventional MRI techniques are insensitive to fiber tract direction and organization, and have not consistently demonstrated white matter abnormalities. DTI may, therefore, provide important new information about neural circuitry, and it is increasingly being used in neuroimaging studies of psychopathological disorders. Of note, in the past five years 18 DTI studies in schizophrenia have been published, most describing white matter abnormalities. Questions still remain, however, regarding what we are measuring that is abnormal in this disease, and how measures obtained using one method correspond to those obtained using other methods? Below we review the basic principles involved in MR-DTI, followed by a review of the different methods used to evaluate diffusion. Finally, we review MR-DTI findings in schizophrenia.