Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers

MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.     

An approach to high resolution diffusion tensor imaging in fixed primate brain

High resolution ex vivo diffusion tensor imaging (DTI) studies of neural tissues can improve our understanding of brain structure. In these studies we can modify the tissue relaxation properties of the fixed tissues to better suite the scanner hardware. We investigated the use of Gd-DTPA contrast agent to provide the optimum signal-to-noise (SNR) ratio in 3D DTI scans of formalin fixed nonhuman primate brains at 4.7 T. Relaxivity measurements in gray and white matter allowed us to optimize the Gd concentration for soaking the brains, resulting in a 2 fold improvement in SNR for the 3D scans. FA changed little with Gd concentrations up to 10 mM although ADC was reduced at 5 and 10 mM. Comparison of in vivo, fresh ex vivo and fixed brains showed no significant FA changes but reductions in ADC of about 50% in fresh ex vivo, and 64% and 80% in fixed gray and white matter respectively. Studies of the temperature dependence of diffusion in these tissues suggested that a 30 degrees increase in sample temperature may yield an improvement of up to 55% in SNR-efficiency for a given diffusion weighting. Our Gd soaking regimen appeared to have no detrimental effect on standard histology of the fixed brain sections. Our methods yield both high SNR and spatial resolution DTI data in fixed primate brains, allowing us to perform high resolution tractography which will facilitate the process of 'validation' of DTI fiber tracts against traditional measures of brain fiber architecture.     

Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water

Myelin loss and axonal damage are both observed in white matter injuries. Each may have significant impact on the long-term disability of patients. Currently, there does not exist a noninvasive biological marker that enables differentiation between myelin and axonal injury. We describe herein the use of magnetic resonance diffusion tensor imaging (DTI) to quantify the effect of dysmyelination on water directional diffusivities in brains of shiverer mice in vivo. The principal diffusion eigenvalues of eight axonal fiber tracts that can be identified with certainty on DTI maps were measured. The water diffusivity perpendicular to axonal fiber tracts, lambda(perpendicular), was significantly higher in shiverer mice compared with age-matched controls, reflecting the lack of myelin and the increased freedom of cross-fiber diffusion in white matter. The water diffusivity parallel to axonal fiber tracts, lambda(parallel), was not different, which is consistent with the presence of intact axons. It is clear that dysmyelination alone does not impact lambda(parallel). The presence of intact axons in the setting of incomplete myelination was confirmed by electron microscopy. Although further validation is still needed, our finding suggests that changes in lambda(perpendicular) and lambda(parallel) may potentially be used to differentiate myelin loss versus axonal injury.     

Characterization of displaced white matter by brain tumors using combined DTI and fMRI

In vivo white matter tractography by diffusion tensor imaging (DTI) has become a popular tool for investigation of white matter architecture in the normal brain. Despite some unresolved issues regarding the accuracy of DTI, recent studies applied DTI for delineating white matter organization in the vicinity of brain lesions and especially brain tumors. Apart from the intrinsic limitations of DTI, the tracking of fibers in the vicinity or within lesions is further complicated due to changes in diseased tissue such as elevated water content (edema), tissue compression and degeneration. These changes deform the architecture of the white matter and in some cases prevent definite selection of the seed region of interest (ROI) from which fiber tracking begins. We show here that for displaced fiber systems, the use of anatomical approach for seed ROI selection yields insufficient results. Alternatively, we propose to select the seed points based on functional MRI activations which constrain the subjective seed ROI selection. The results are demonstrated on two major fiber systems: the pyramidal tract and the superior longitudinal fasciculus that connect critical motor and language areas, respectively. The fMRI based seed ROI selection approach enabled a more comprehensive mapping of these fiber systems. Furthermore, this procedure enabled the characterization of displaced white matter using the eigenvalue decomposition of DTI. We show that along the compressed fiber system, the diffusivity parallel to the fiber increases, while that perpendicular to the fibers decreases, leading to an overall increase in the fractional anisotropy index reflecting the compression of the fiber bundle. We conclude that definition of the functional network of a subject with deformed white matter should be done carefully. With fMRI, one can more accurately define the seed ROI for DTI based tractography and to provide a more comprehensive, functionally related, white matter mapping, a very important tool used in pre-surgical mapping.     

3D fiber tractography with susceptibility tensor imaging

Gradient-echo MRI has revealed anisotropic magnetic susceptibility in the brain white matter. This magnetic susceptibility anisotropy can be measured and characterized with susceptibility tensor imaging (STI). In this study, a method of fiber tractography based on STI is proposed and demonstrated in the mouse brain. STI experiments of perfusion-fixed mouse brains were conducted at 7.0 T. The magnetic susceptibility tensor was calculated for each voxel with regularization and decomposed into its eigensystem. The major eigenvector is found to be aligned with the underlying fiber orientation. Following the orientation of the major eigenvector, we are able to map distinctive fiber pathways in 3D. As a comparison, diffusion tensor imaging (DTI) and DTI fiber tractography were also conducted on the same specimens. The relationship between STI and DTI fiber tracts was explored with similarities and differences identified. It is anticipated that the proposed method of STI tractography may provide a new way to study white matter fiber architecture. As STI tractography is based on physical principles that are fundamentally different from DTI, it may also be valuable for the ongoing validation of DTI tractography.     

Quantitative tract-based white matter development from birth to age 2years

Few large-scale studies have been done to characterize the normal human brain white matter growth in the first years of life. We investigated white matter maturation patterns in major fiber pathways in a large cohort of healthy young children from birth to age two using diffusion parameters fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (RD). Ten fiber pathways, including commissural, association and projection tracts, were examined with tract-based analysis, providing more detailed and continuous spatial developmental patterns compared to conventional ROI based methods. All DTI data sets were transformed to a population specific atlas with a group-wise longitudinal large deformation diffeomorphic registration approach. Diffusion measurements were analyzed along the major fiber tracts obtained in the atlas space. All fiber bundles show increasing FA values and decreasing radial and axial diffusivities during development in the first 2years of life. The changing rates of the diffusion indices are faster in the first year than the second year for all tracts. RD and FA show larger percentage changes in the first and second years than AD. The gender effects on the diffusion measures are small. Along different spatial locations of fiber tracts, maturation does not always follow the same speed. Temporal and spatial diffusion changes near cortical regions are in general smaller than changes in central regions. Overall developmental patterns revealed in our study confirm the general rules of white matter maturation. This work shows a promising framework to study and analyze white matter maturation in a tract-based fashion. Compared to most previous studies that are ROI-based, our approach has the potential to discover localized development patterns associated with fiber tracts of interest.     

Diffusion tensor imaging of white matter tract evolution over the lifespan

Diffusion tensor imaging (DTI) has been used widely to show structural brain changes during both development and aging. Lifespan studies are valuable because they connect these two processes, yet few DTI studies have been conducted that include both children and elderly subjects. This study used DTI tractography to investigate 12 major white matter connections in 403 healthy subjects aged 5-83 years. Poisson fits were used to model changes of fractional anisotropy (FA) and mean diffusivity (MD) across the age span, and were highly significant for all tracts. FA increased during childhood and adolescence, reached a peak between 20 and 42 years of age, and then decreased. MD showed an opposite trend, decreasing first, reaching a minimum at 18-41 years, and then increasing later in life. These trajectories demonstrate rates and timing of development and degradation that vary regionally in the brain. The corpus callosum and fornix showed early reversals of development trends, while frontal-temporal connections (cingulum, uncinate, superior longitudinal) showed more prolonged maturation and delayed declines. FA changes were driven by perpendicular diffusivity, suggesting changes of myelination and/or axonal density. Tract volume changed significantly with age for most tracts, but did not greatly influence the FA and MD trajectories. This study demonstrates clear age-related microstructural changes throughout the brain white matter, and provides normative data that will be useful for studying white matter development in a variety of diseases and abnormal conditions.     

The effects of brain tissue decomposition on diffusion tensor imaging and tractography

There have been numerous high resolution diffusion tensor imaging studies in fixed animal brains, but relatively few studies in human brains. While animal tissues are generally fixed pre-mortem or directly postmortem, this is not possible for human tissue, therefore there is always some delay between death and tissue fixation. The elapsed time between death and tissue fixation, the postmortem interval (PMI), will most likely adversely affect the tissue's diffusion properties. We studied the effects of PMI on the diffusion properties of rodent brain. Eight mice were euthanized and the brains (kept in the skull) were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography was also performed. The temporal changes in regional ADC and FA values were analyzed statistically using a one-way ANOVA, followed by individual Student's T-tests. Regional FA and ADC of gray and white matter decreased significantly with time (p<0.05). DTI tractography showed a decrease in the number and coherence of reconstructed fiber pathways between PMIs 0 and 14. Elapsed time between death and tissue fixation has a major effect upon the brain's diffusion properties and should be born in mind when interpreting fixed brain DTI.     

Reproducibility of quantitative tractography methods applied to cerebral white matter

Tractography based on diffusion tensor imaging (DTI) allows visualization of white matter tracts. In this study, protocols to reconstruct eleven major white matter tracts are described. The protocols were refined by several iterations of intra- and inter-rater measurements and identification of sources of variability. Reproducibility of the established protocols was then tested by raters who did not have previous experience in tractography. The protocols were applied to a DTI database of adult normal subjects to study size, fractional anisotropy (FA), and T2 of individual white matter tracts. Distinctive features in FA and T2 were found for the corticospinal tract and callosal fibers. Hemispheric asymmetry was observed for the size of white matter tracts projecting to the temporal lobe. This protocol provides guidelines for reproducible DTI-based tract-specific quantification.     

Problem solving, working memory, and motor correlates of association and commissural fiber bundles in normal aging: a quantitative fiber tracking study

Normal aging is accompanied by decline in selective cognitive and motor functions. A concurrent decline in regional white matter integrity, detectable with diffusion tensor imaging (DTI), potentially contributes to waning function. DTI analysis of white matter loci indicates an anterior-to-posterior gradient distribution of declining fractional anisotropy (FA) and increasing diffusivity with age. Quantitative fiber tracking can be used to determine regional patterns of normal aging of fiber systems and test the functional ramifications of the DTI metrics. Here, we used quantitative fiber tracking to examine age effects on commissural (genu and splenium), bilateral association (cingulate, inferior longitudinal fasciculus and uncinate), and fornix fibers in 12 young and 12 elderly healthy men and women and tested functional correlates with concurrent assessment of a wide range of neuropsychological abilities. Principal component analysis of cognitive and motor tests on which the elderly achieved significantly lower scores than the young group was used for data reduction and yielded three factors: Problem Solving, Working Memory, and Motor. Age effects--lower FA or higher diffusivity--in the elderly were prominent in anterior tracts, specifically, genu, fornix, and uncinate fibers. Differential correlations between FA or diffusivity in fiber tracts and scores on Problem Solving, Working Memory, or Motor factors provide convergent validity to the biological meaningfulness of the integrity of the fibers tracked. The observed pattern of relations supports the possibility that regional degradation of white matter fiber integrity is a biological source of age-related functional compromise and may have the potential to limit accessibility to alternative neural systems to compensate for compromised function.     

Investigating cervical spinal cord structure using axial diffusion tensor imaging

This study describes a new technique for Diffusion Tensor Imaging (DTI) that acquires axial (transverse) images of the cervical spinal cord. The DTI images depict axonal fiber orientation, enable quantification of diffusion characteristics along the spinal cord, and have the potential to demonstrate the connectivity of cord white matter tracts. Because of the high sensitivity to motion of diffusion-weighted magnetic resonance imaging and the small size of the spinal cord, a fast imaging method with high in-plane resolution was developed. Images were acquired with a single-shot EPI technique, named ZOOM-EPI (zonally magnified oblique multislice echo planar imaging), which selects localized areas and reduces artefacts caused by susceptibility changes between soft tissue and the adjacent vertebrae. Cardiac gating was used to reduce pulsatile flow artefacts from the surrounding cerebrospinal fluid. Voxel resolution was 1.25 x 1.25 mm(2) in-plane with 5-mm slice thickness. Both the mean diffusivity (MD) and the fractional anisotropy (FA) indices of the cervical spinal cord were measured. The FA index demonstrated high anisotropy of the spinal cord with an average value of 0.61 +/- 0.05 (highest value of 0.66 +/- 0.03 at C3), comparable to white matter tracts in the brain. The diffusivity components parallel and orthogonal to the longitudinal axes of the cord were lambda( parallel) = (1648 +/- 123) x 10(-6) mm(2)s(-1) and lambda( perpendicular) = (570 +/- 47) x 10(-6) mm(2) s(-1), respectively. The high axial resolution allowed preliminary evaluation of fiber connectivity using the fast-marching tractography algorithm, which generated traces of fiber paths consistent with the well-known cord anatomy.     

Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns

Magnetic resonance diffusion tensor imaging (DTI) enables the discrimination of white matter pathways before myelination is evident histologically or on conventional MRI. In this investigation, 14 premature neonates with no evidence of white matter abnormalities by conventional MRI were studied with DTI. A custom MR-compatible incubator with a novel high sensitivity neonatal head coil and improved acquisition and processing techniques were employed to increase image quality and spatial resolution. The technical improvements enabled tract-specific quantitative characterization of maturing white matter, including several association tracts and subcortical projection tracts not previously investigated in neonates by MR. Significant differences were identified between white matter pathways, with earlier maturing commissural tracts of the corpus callosum, and deep projection tracts of the cerebral peduncle and internal capsule exhibiting lower mean diffusivity (Dav) and higher fractional anisotropy (FA) than later maturing subcortical projection and association pathways. Maturational changes in white matter tracts included reductions in Dav and increases in FA with age due primarily to decreases in the two minor diffusion eigenvalues (lambda2 and lambda3). This work contributes to the understanding of normal white matter development in the preterm neonatal brain, an important step toward the use of DTI for the improved evaluation and treatment of white matter injury of prematurity.     

磁共振弥散张量成像定量分析复发-缓解型多发性硬化患者表现正常的脑干白质纤维束

目的 应用磁共振弥散张量成像(DTI)定量分析复发-缓解型多发性硬化(RRMS)患者表现正常的脑干白质纤维束的改变.方法 对50例RRMS患者(RRMS组)及25名年龄和性别相匹配的健康志愿者(对照组)行磁共振扫描,获取常规MR图像和DTI图像.比较两组脑干主要纤维束(皮质脊髓束/皮质脑桥束、小脑上、中、下脚纤维束和内侧丘系纤维束)的部分各向异性分数(FA)和平均弥散系数(MD)的变化.结果 排除年龄、性别等因素影响后,经ANCOVA协方差分析,RRMS组患者皮质脊髓束/皮质脑桥束(L:P=0.030;R:P=0.020)、小脑下脚(L:P=0.030;R:P=0.037)、小脑上脚(L:P=0.036;R:P=0.041)、内侧丘系(L:P=0.014;R:P=0.035)的FA值较对照组明显降低.RRMS组患者皮质脊髓束/皮质脑桥束(L:P=0.004;R:P=0.046)、小脑下脚(L:P=0.047;R:P=0.011)、小脑上脚(L:P=0.021;R:P=0.011)、内侧丘系(L:P=0.002;R:P=0.044)的MD值较对照组明显增高.小脑中脚的MD值及FA值两组间差异均无统计学意义(P＞0.05).RRMS患者表现正常脑干白质纤维束的MD值及FA值与脑实质分数(BPF)、T2病灶容积之间均无相关性.结论 RRMS患者表现正常脑干白质纤维束DTI的异常发现,提示上述纤维束存在微观病变,推测病变可能是局部隐匿性病灶导致的髓鞘脱失、轴突破坏.     

DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.     

Longitudinal changes in grey and white matter during adolescence

Brain development continues actively during adolescence. Previous MRI studies have shown complex patterns of apparent loss of grey matter (GM) volume and increases in white matter (WM) volume and fractional anisotropy (FA), an index of WM microstructure. In this longitudinal study (mean follow-up = 2.5 ± 0.5 years) of 24 adolescents, we used a voxel-based morphometry (VBM)-style analysis with conventional T1-weighted images to test for age-related changes in GM and WM volumes. We also performed tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to test for age-related WM changes across the whole brain. Probabilistic tractography was used to carry out quantitative comparisons across subjects in measures of WM microstructure in two fiber tracts important for supporting speech and motor functions (arcuate fasciculus [AF] and corticospinal tract [CST]). The whole-brain analyses identified age-related increases in WM volume and FA bilaterally in many fiber tracts, including AF and many parts of the CST. FA changes were mainly driven by increases in parallel diffusivity, probably reflecting increases in the diameter of the axons forming the fiber tracts. FA values of both left and right AF (but not of the CST) were significantly higher at the end of the follow-up than at baseline. Over the same period, widespread reductions in the cortical GM volume were found. These findings provide imaging-based anatomical data suggesting that brain maturation in adolescence is associated with structural changes enhancing long-distance connectivities in different WM tracts, specifically in the AF and CST, at the same time that cortical GM exhibits synaptic “pruning”.     

A comprehensive reliability assessment of quantitative diffusion tensor tractography

Diffusion tensor tractography is increasingly used to examine structural connectivity in the brain in various conditions, but its test-retest reliability is understudied. The main purposes of this study were to evaluate 1) the reliability of quantitative measurements of diffusion tensor tractography and 2) the effect on reliability of the number of gradient sampling directions and scan repetition. Images were acquired from ten healthy participants. Ten fiber regions of nine major fiber tracts were reconstructed and quantified using six fiber variables. Intra- and inter-session reliabilities were estimated using intraclass correlation coefficient (ICC) and coefficient of variation (CV), and were compared to pinpoint major error sources. Additional pairwise comparisons were made between the reliability of images with 30 directions and NEX 2 (DTI30-2), 30 directions and NEX 1 (DTI30-1), and 15 directions and NEX 2 (DTI15-2) to determine whether increasing gradient directions and scan repetition improved reliability. Of the 60 tractography measurements, 43 showed intersession CV ≤ 10%, ICC ≥ .70, or both for DTI30-2, 40 measurements for DTI30-1, and 37 for DTI15-2. Most of the reliable measurements were associated with the tracts corpus callosum, cingulum, cerebral peduncular fibers, uncinate fasciculus, and arcuate fasciculus. These reliable measurements included factional anisotropy (FA) and mean diffusivity of all 10 fiber regions. Intersession reliability was significantly worse than intra-session reliability for FA, mean length, and tract volume measurements from DTI15-2, indicating that the combination of MRI signal variation and physiological noise/change over time was the major error source for this sequence. Increasing the number of gradient directions from 15 to 30 while controlling the scan time, significantly affected values for all six variables and reduced intersession variability for mean length and tract volume measurements. Additionally, while increasing scan repetition from 1 to 2 had no significant effect on the reliability for DTI with 30 directions, this significantly reduced the upward bias in FA values from all 10 fiber regions and fiber count, mean length, and tract volume measurements from 5 to 7 fiber regions. In conclusion, diffusion tensor tractography provided many measurements with high test-retest reliability across different fiber variables and various fiber tracts even for images with 15 directions (NEX 2). Increasing the number of gradient directions from 15 to 30 with equivalent scan time reduced variability whereas increasing repetition from 1 to 2 for 30-direction DTI improved the accuracy of tractography measurements.     

基于纤维束骨架的空间统计方法研究维持性透析终末期肾病患者脑白质结构变化

目的 探讨基于纤维束骨架的空间统计方法研究维持性透析终末期肾病（ESRD）患者脑白质微结构变化。方法 采用3.0T MR仪对32例行维持性血透的ESRD患者和30名健康对照行DTI扫描,应用基于纤维束骨架的空间统计（TBSS）方法分析DTI多参数图,获得部分各向异性分数（FA）、平均弥散度（MD）、轴向弥散度（AD）及径向弥散度（RD）有显著差异的脑区。将ESRD患者差异脑区FA值与简易精神状态测试（MMSE）评分进行偏相关分析。结果 与健康对照比较,ESRD患者双侧额叶白质、双侧前辐射冠、胼胝体体部及膝部、左侧颞叶白质及多条联络纤维FA值显著减低;MD值呈广泛且对称性显著升高;右侧上纵束、左侧上辐射冠AD值显著升高,左侧丘脑前辐射AD值显著降低;双侧额叶、胼胝体及双侧上纵束等白质区RD值显著升高（P均<0.05）。右侧额叶白质（r=0.404,P=0.022）及左侧上纵束（r=0.475,P=0.006）FA值与MMSE评分呈正相关。结论 ESRD患者脑区白质微结构受损,可能导致其认知障碍。     

Corpus callosal diffusivity predicts motor impairment in relapsing-remitting multiple sclerosis: a TBSS and tractography study

Motor deficits in relapsing remitting multiple sclerosis (RRMS) patients are monitored using standard measures of disability that assess performance ranging from walking ability to hand function, thus reflecting involvement of a variety of motor pathways. We investigated the relative contributions of diffuse white matter damage and focal lesions using diffusion tensor imaging (DTI), in predicting future worsening of hand function in RRMS. The nine hole peg test (NHPT), a test of fine hand motor control, was used to measure baseline upper limb function in 16 controls and 25 RRMS patients, and then performed at follow-up on 22 of these patients at 6 and 12 months. Tract-based spatial statistics (TBSS) were used across the whole brain as a non-hypothesis driven method for localizing white matter changes associated with motor deficits. Subsequently, we used probabilistic fiber tractography in the corticospinal tracts (CST) and the transcallosal hand motor (TCHM) fibers to assess the predictive power of diffusion metrics and/or functionally relevant visible lesion volumes on the decline of hand motor function over the next 12 months. While fractional anisotropy (FA) and radial diffusivity (RD) of both pathways were strongly associated with NHPT performance at baseline, only RD of the TCHM fibers was predictive of NHPT decline over the next 12 months. Neither total visible lesion load nor pathway specific lesion loads were indicative of NHPT performance or progression. The TCHM fibers may play an important role in modifying the effects of MS pathology on fine motor control, and RD in these fibers may be a sensitive biomarker for future disability.     

Bootstrap white matter tractography (BOOT-TRAC)

White matter tractography is a noninvasive method for estimating and visualizing the white matter connectivity patterns in the human brain using diffusion tensor imaging (DTI) data. Sources of experimental noise may induce errors in the measured fiber directions, which will reduce the accuracy of the estimated white matter trajectories. In this study, a statistical nonparametric bootstrap method is described for estimating the dispersion and other errors in white matter tractography results. Prior studies have derived models of tractography error using the signal-to-noise ratio (SNR) and diffusion anisotropy of the DTI data. Tractography errors measured using bootstrap methods were generally consistent with an analytic model of tractography error except in areas where branching was evident. White matter tractography with bootstrap resampling is also applied to estimate the probabilities of connection between brain regions. The approach was used to generate probabilistic connectivity maps between the cerebral peduncles and specific cortical regions.     

Microstructure of a three-way anatomical network predicts individual differences in response inhibition: a tractography study

Response inhibition is thought to depend critically on the inferior frontal gyrus, pars opercularis (IFGoper), presupplementary motor area (preSMA) and basal ganglia, including the subthalamic nucleus (STN), but the differential contribution of structural connections within this network to response inhibition remains unclear. Using diffusion tensor imaging and probabilistic fiber tractography, we investigated the relative associations between local white matter microstructure and stop-signal response inhibition in fronto-basal ganglia tracts delineated by probabilistic tractography. In a tract-of-interest approach, we identify significant associations with fractional anisotropy (FA) in fibers connecting the right STN region to both preSMA/SMA and IFGoper and in bilateral tracts connecting preSMA/SMA to IFGoper and the striatum. In addition, significant associations with radial diffusivity (RD) were found in fibers connecting the right preSMA/SMA to striatum and in bilateral tracts between IFGoper and STN region. In our whole-brain analysis, additional significant clusters were identified in the corpus callosum, optic radiation, inferior fronto-occipital tract and white matter of the precentral gyrus. To investigate the relative importance of regional white matter characteristics to response inhibition performance, we performed a step-wise multiple regression analysis that yielded FA in tracts connecting preSMA/SMA to the STN region and striatum, respectively, and RD in fibers connecting IFGoper to the STN region as best predictors of response inhibition performance (42% explained variance). These findings point to a specific contribution of white matter pathways connecting distinct basal ganglia structures with both medial frontal and ventrolateral prefrontal regions to response inhibition.