White matter tractography using diffusion tensor deflection

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions.     

Thalamo‐frontal white matter alterations in chronic schizophrenia

Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo‐frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography‐based and voxel‐based studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal capsule (IC) region of interest (ROI) as “source”, and different Brodmann area (BA) ROIs as “targets”. The resulting bundles are then longitudinally parameterized so that diffusion properties can be measured and compared along the WMT. Using this processing pipeline, we were able to find altered diffusion properties in male patients with chronic schizophrenia in terms of fractional anisotropy (FA) decreases and mean diffusivity (MD) increases in precise and functionally relevant locations. These findings suggest that our method can enhance the regional and functional specificity of DTI group studies, thus improving our understanding of brain function. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Diffusion tensor imaging and tractography of central pontine myelinolysis

OBJECTIVES: To illustrate the value of diffusion tensor imaging and tractography in the diagnosis and follow-up of central pontine myelinolysis. CASE REPORT: We report a case of central pontine myelinolysis in a 29 year old woman, also anorexic, studied using MR Diffusion Tensor Imaging (DTI) and Fibre Tracking (FT) focused on the pons, and compared with the studies of 5 normal volunteers. Tractography showed a swollen aspect of the right corticospinal fiber tract correlating with mild left lower extremity deficit at clinical evaluation. The pontine fibers were posteriorly displaced but intact. The sensory tracts were also intact. Apparent Diffusion Coefficient values were increased and Fractional Anisotropy was decreased in the lesions. Follow up imaging showed persistent abnormal ADC and FA values in the pons although the left cortico-spinal tract returned to normal, consistent with the clinical outcome. CONCLUSION: Diffusion Tensor Imaging MR and Fiber tractography are a new method to analyse white matter tracts. It can be used to prospectively evaluate the location of white matter tract lesions at the acute phase of central pontine myelinolysis and follow up.     

白质纤维束示踪成像技术在高血压脑出血中的初步应用

目的探讨白质纤维束示踪成像技术在高血压脑出血中的临床应用价值。方法对我院8例急性期情况稳定的高血压脑出血患者进行磁共振弥散张量成像,应用日本东京大学的Volume-one1.72和Diffusion Ten-sor Visualizer(dTV)软件进行三维白质纤维束示踪成像,观察以内囊为主的白质纤维束的压迫、推移、破坏情况。结果8例患者均行磁共振弥散张量成像并行内囊白质纤维束示踪成像,可清楚看到内囊白质纤维束受血肿压迫、推移、破坏情况,由患侧内囊追踪到的相对纤维束条目数少于健侧内囊(P<0.005)。结论白质纤维束示踪成像技术可以清楚显示高血压脑出血后内囊白质纤维束的受累情况。     

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.     

Can spherical deconvolution provide more information than fiber orientations? Hindrance modulated orientational anisotropy,a true‐tract specific index to characterize white matter diffusion

Diffusion tensor imaging (DTI) methods are widely used to reconstruct white matter trajectories and to quantify tissue changes using the average diffusion properties of each brain voxel. Spherical deconvolution (SD) methods have been developed to overcome the limitations of the diffusion tensor model in resolving crossing fibers and to improve tractography reconstructions. However, the use of SD methods to obtain quantitative indices of white matter integrity has not been extensively explored. In this study, we show that the hindrance modulated orientational anisotropy (HMOA) index, defined as the absolute amplitude of each lobe of the fiber orientation distribution, can be used as a compact measure to characterize the diffusion properties along each fiber orientation in white matter regions with complex organization. We demonstrate that the HMOA is highly sensitive to changes in fiber diffusivity (e.g., myelination processes or axonal loss) and to differences in the microstructural organization of white matter like axonal diameter and fiber dispersion. Using simulations to describe diffusivity changes observed in normal brain development and disorders, we observed that the HMOA is able to identify white matter changes that are not detectable with conventional DTI indices. We also show that the HMOA index can be used as an effective threshold for in vivo data to improve tractography reconstructions and to better map white matter complexity inside the brain. In conclusion, the HMOA represents a true tract‐specific and sensitive index and provides a compact characterization of white matter diffusion properties with potential for widespread application in normal and clinical populations. Hum Brain Mapp 34:2464–2483, 2013. © 2012 Wiley Periodicals, Inc.     

Late measures of microstructural alterations in severe neonatal hypoxic–ischemic encephalopathy by MR diffusion tensor imaging

Neonatal hypoxic–ischemic encephalopathy is a major cause of brain damage in infants, and is associated with periventricular white matter injury and chronic neurological dysfunctions. However, the mechanisms of the chronic white matter injury and reorganization are still unclear. In this study, in vivo diffusion tensor imaging (DTI) was employed to evaluate the late changes of white matter microstructural integrity in the rat brains at 10 weeks after severe neonatal hypoxic–ischemic insults at postnatal day 7. In the fractional anisotropy directionality map, qualitative evaluation showed that a dorsoventrally oriented fiber bundle extended from the corpus callosum into the cyst in the anterior brain, whilst the posterior peri-infarct areas had similar fiber orientations as the contralateral internal capsule, optic tract and fimbria of hippocampus. Compared to the contralateral hemisphere, significantly higher fractional anisotropy, axial diffusivity and diffusion trace value were observed quantitatively in the distal end of the extended fiber bundle connecting the anterior and posterior white matters rostrocaudally. A significantly lower fractional anisotropy but higher axial and radial diffusivities and trace were also found in the ipsilateral corpus callosum, proximal external capsule and anterior commissure, while slightly lower fractional anisotropy and axial diffusivity were noticed in the ipsilateral internal capsule and optic nerve. It was suggested that increased fractional anisotropy, axial diffusivity and trace characterize white matter reorganization in chronic neonatal hypoxic–ischemic insults, whereas reduction in fractional anisotropy appears to characterize two types of white matter lesions, with significantly higher axial and radial diffusivities and trace being primary and slightly lower axial diffusivity being secondary. Combined with fractional anisotropy directionality map, in vivo DTI provides important indices to differentiate the chronic effects of severe neonatal hypoxic–ischemic injury and recovery globally, quantitatively and non-invasively.     

Isolated motor neglect following infarction of the posterior limb of the right internal capsule: a case study with diffusion tensor imaging-based tractography

Motor neglect is an impairment in the ability to initiate movement not attributable to muscle weakness. The neural network of this syndrome is not precisely defined. We present the diffusion tensor imaging (DTI)-base tractography findings in an acute stroke patient presenting with isolated motor neglect following infarction in the posterior limb of the internal capsule within the anterior choroidal artery territory. A left-handed 17-year-old woman presented with an acute onset of motor neglect of her left arm. Motor tasks performed with the affected limb were awkward; however, the tasks could be accomplished with effort. Magnetic resonance imaging (MRI) including DTI of the brain were performed. DTI-based tractography extracted the fiber tracts originating from regions of interest placed on the ischemic lesion. MRI revealed an acute ischemic infarction at the posterior part of the posterior limb of the right internal capsule within the territory of the anterior choroidal artery. DTI-based tractography showed fiber tracts projecting from the lesion to the posterior part of the supplementary motor area and some fiber tracts projecting to posterior aspects of the thalamus. DTI-based tractography may be a useful tool for visualizing white matter pathways in vivo following an acute infarction. Our case study supports the notion that fiber tracts connecting the posterior part of the posterior limb of the internal capsule, supplementary motor area, and posterior aspect of the thalamus are key areas of a neural network involved in motor neglect syndrome.     

Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis

BACKGROUND: Histopathological studies of amyotrophic lateral sclerosis (ALS) are of end stage disease. Diffusion tensor imaging (DTI) provides the opportunity to investigate indirectly corticospinal tract pathology of ALS in vivo. METHODS: DTI was used to study the water diffusion characteristics of the corticospinal tracts in 21 patients with ALS and 14 normal controls. The authors measured the fractional anisotropy (FA) and mean diffusivity (MD) along the pyramidal tracts from the internal capsules down to the pyramids. A mixed model regression analysis was used to compare FA and MD between the ALS and control groups. RESULTS: FA showed a downward linear trend from the cerebral peduncles to the pyramids and was lower in the ALS group than controls at multiple levels of the corticospinal tract. At the internal capsules, FA was higher on the right. MD showed an upward trend, progressing caudally from the internal capsules to the pyramids. MD was higher at the level of the internal capsule in the ALS group, but caudally this difference was not maintained. No correlations were found between clinical markers of disability and water diffusion indices. CONCLUSIONS: These findings provide insights into the pathological processes of ALS. Differences in diffusion characteristics at different anatomical levels may relate to underlying tract architecture or the distribution of pathological damage in ALS. Further development may permit monitoring of progression and treatment of disease.     

Evaluation of white matter integrity in ex vivo brains of amyloid plaque-bearing APPsw transgenic mice using magnetic resonance diffusion tensor imaging

Magnetic resonance diffusion tensor imaging (DTI) was used to examine the integrity of midline white matter tracts in APPsw (Tg2576) transgenic mice, a mouse-model of cerebral amyloid deposition. Ex vivo DTI was performed on formalin-fixed brains from APPsw and age-matched transgene-negative control mice at the ages of 12, 15, and 17 months. The characteristics of water diffusion in six midline white matter tracts were quantified using four metrics: relative anisotropy (RA), mean diffusivity, axial diffusivity, and radial diffusivity. Two-way ANOVA analyses indicated a significant main effect of transgene on RA in the corpus callosum (CC) and ventral hippocampal commissure (VHC), due to small reductions (2-6%) in RA in APPsw mice relative to age-matched control mice. However, these reductions were not significant at any specific age group and were not progressive with increasing age. The other diffusion metrics exhibited no significant differences between APPsw and control mice in the CC and VHC, nor did any of the diffusion metrics exhibit significant differences between APPsw and control mice in other midline white matter tracts (anterior commissure, posterior commissure, fornix, and dorsal fornix). Overall, these results indicate that white matter integrity, as measured by ex vivo DTI, is predominately unaltered in formalin-fixed brains from amyloid plaque-bearing APPsw mice.     

Diffusion tensor imaging tractography and reliability analysis for limbic and paralimbic white matter tracts

Diffusion tensor imaging (DTI) provides the opportunity to study white matter tracts in vivo. The goal was to estimate the reliability of DTI tractography for the analysis of limbic and paralimbic white matter. Normative data from 24 healthy subjects and reliability data from four healthy and four depressed subjects were acquired at 1.5 Tesla, using twice-refocused spin-echo, echoplanar DTI and Fluid-Attenuated Inversion Recovery (FLAIR) DTI sequences. Fiber tracking was performed using the Fiber Assignment by Continuous Tracking algorithm. Fractional Anisotropy (FA), trace Apparent Diffusion Coefficient and tract volumes were calculated. The inter-rater (and intra-rater) intraclass correlation coefficients for FA values were as follows: rostral cingulum 0.89 (0.87), dorsal cingulum 0.85 (0.90), parahippocampal cingulum 0.85 (0.95), uncinate fasciculus 0.85 (0.87), medial prefrontal white matter 0.97 (0.99), ventromedial prefrontal white matter 0.92 (0.93), crus of fornix 0.80 (0.81). The reported DTI protocol provides a reliable method to analyze limbic and paralimbic white matter tracts relevant to psychiatric disorders.     

磁共振张量成像对脑梗死预后的评价

目的利用磁共振弥散张量成像(DTI)探讨脑梗死病人脑白质纤维束各向异性特征和白质纤维束受损与临床预后关系。方法对23例脑梗死患者行DTI检查,以三维立体弥散张量成像为基础的色彩图进行图像后处理,评价脑梗死区周边纤维束的情况,将纤维束分为受压移位、变细萎缩和破坏中断三类,并与临床预后、神经功能缺损程度比较。结果三维成像所见与病人预后关系密切。所有脑白质纤维束萎缩和中断的患者,在随访过程中存在不同程度脑功能损伤,而脑白质受压移位的病人神经功能完全或近乎完全恢复。结论在脑梗死中,DTI能直接观察到白质纤维束的变化,对于评估临床预后具有重要作用。     

磁共振弥散张量成像对功能区脑肿瘤手术的参考价值

[目的]评价磁共振弥散张量成像(DTI)对功能区脑肿瘤手术的指导意义和应用价值.[方法]对25例患者行头部DTI检查,立体显示肿瘤与脑白质纤维束的关系,术前评估,设计手术入路,对所有病例行显微外科肿瘤切除手术治疗.[结果]本组脑肿瘤中累及脑白质纤维束区域主要位于锥体束和内囊,其中脑白质纤维束破坏13例,移位12例.肿瘤全切除11例,次全切除14例,无手术死亡.术前存在脑白质纤维束受累所致的神经功能阳性体征者术后改善13例,无变化者10例,加重2例.[结论]DTI能够清晰显示脑肿瘤对白质纤维束的累及关系,对神经外科优化手术设计、决定手术切除范围和评估术后神经功能具有指导意义.     

Principles of diffusion-weighted MR imaging and application to clinical neurology]

Diffusion-weighted Imaging (DWI) is a advantageous method for early detection of cerebral ischemia. DWI with echo-planar sequence (EP-DWI) offers multisectional images sensitive to cytotoxic edema in a very short aquisition time and is almost free from motion artifact. However, the susceptibility artifacts and low spatial resolution of EP-DWI must be improved. In estimation of DWI, influence of T2 must be considered, because DWI is almost always based on T2-weighted imaging. DWI is applied to other cerebral disorders such as degenerative and demyelinating disease, infectious disease, tumors or so. In order to demonstrate water diffusion precisely, diffusion tensor imaging (DTI) must be introduced and applied to anisotropy indices such as fractional anisotropy (FA) and depiction of neurofiber direction, tractography. Measurements of FA in various degenerative diseases may contribute to differentiation in normal appearing white matter. Diffusion tensor tractography may provide more information about relationship of major white matter tract such as corticospinal tract with brain lesion. Furthermore, DWI and DTI are expected to demonstrate diffusion of protons of aminoacids such as choline, creatine, NAA and provide more pertinent information of regional pathologic state of the brain in future.     

Diffusion Tensor Tractography in Hypothyroidism and its Correlation with Memory Function

Diffusion tensor tractography (DTT) was performed to determine the microstructural changes in the white matter fibre tracts of hypothyroid patients compared to controls and to correlate these changes with memory dysfunction scores. DTT and Postgraduate Institute Memory Scale test were performed in eight hypothyroid patients and eight healthy controls. Diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was made between the patient group and controls. Pearson's correlation was performed between Memory Dysfunction score and DTI measures. Significant changes in DTI measures were observed in various white matter fibre tracts in hypothyroid patients compared to controls. In hypothyroid patients, an inverse correlation of Memory Dysfunction score with FA was observed in the right and left inferior fronto‐occipital fasciculus, whereas a positive correlation with MD was observed in the right anterior thalamic radiation among all white matter tracts. These findings suggest that microstructural changes in white matter fibres may contribute to the underlying dysfunction in memory in hypothyroid patients.     

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.     

Regional variation of white matter development in the cat brain revealed by ex vivo diffusion MR tractography

Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage.     

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.