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1.  Improving diffusion-weighted imaging of post-mortem human brains: SSFP at 7 T 
Neuroimage  2014;102:579-589.
Post-mortem diffusion imaging of whole, human brains has potential to provide data for validation or high-resolution anatomical investigations. Previous work has demonstrated improvements in data acquired with diffusion-weighted steady-state free precession (DW-SSFP) compared with conventional diffusion-weighted spin echo at 3 T. This is due to the ability of DW-SSFP to overcome signal-to-noise and diffusion contrast losses brought about by tissue fixation related decreases in T2 and ADC. In this work, data of four post-mortem human brains were acquired at 3 T and 7 T, using DW-SSFP with similar effective b-values (beff ~ 5150 s/mm2) for inter-field strength comparisons; in addition, DW-SSFP data were acquired at 7 T with higher beff (~ 8550 s/mm2) for intra-field strength comparisons. Results demonstrate that both datasets acquired at 7 T had higher SNR and diffusion contrast than data acquired at 3 T, and data acquired at higher beff had improved diffusion contrast than at lower beff at 7 T. These results translate to improved estimates of secondary fiber orientations leading to higher fidelity tractography results compared with data acquired at 3 T. Specifically, tractography streamlines of cortical projections originating from the corpus callosum, corticospinal tract, and superior longitudinal fasciculus were more successful at crossing the centrum semiovale and projected closer to the cortex. Results suggest that DW-SSFP at 7 T is a preferential method for acquiring diffusion-weighted data of post-mortem human brain, specifically where the primary region of interest involves crossing white matter tracts.
Highlights
•Diffusion weighted SSFP imaging of post-mortem human brain at 7 T is compared to 3 T.•Both SNR and diffusion contrast are improved at 7 T.•7 T data show improved crossing fiber estimates and accompanying tractography.•Including B1 map in 7 T data analysis brings diffusion metrics in line with 3 T data.
doi:10.1016/j.neuroimage.2014.08.014
PMCID: PMC4229505  PMID: 25128709
Post-mortem human brain; Diffusion-weighted steady-state free precession; 7 T; Tractography; Diffusion tensor imaging; MRI
2.  Advances in diffusion MRI acquisition and processing in the Human Connectome Project 
NeuroImage  2013;80:125-143.
The Human Connectome Project (HCP) is a collaborative 5-year effort to map human brain connections and their variability in healthy adults. A consortium of HCP investigators will study a population of 1200 healthy adults using multiple imaging modalities, along with extensive behavioral and genetic data. In this overview, we focus on diffusion MRI (dMRI) and the structural connectivity aspect of the project. We present recent advances in acquisition and processing that allow us to obtain very high-quality in-vivo MRI data, while enabling scanning of a very large number of subjects. These advances result from 2 years of intensive efforts in optimising many aspects of data acquisition and processing during the piloting phase of the project. The data quality and methods described here are representative of the datasets and processing pipelines that will be made freely available to the community at quarterly intervals, beginning in 2013.
doi:10.1016/j.neuroimage.2013.05.057
PMCID: PMC3720790  PMID: 23702418
3.  The Minimal Preprocessing Pipelines for the Human Connectome Project 
NeuroImage  2013;80:105-124.
The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinates spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCP’s acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements for the pipelines.
doi:10.1016/j.neuroimage.2013.04.127
PMCID: PMC3720813  PMID: 23668970
Human Connectome Project; Image Analysis Pipeline; Surface-based Analysis; CIFTI; Grayordinates; Multi-modal Data Integration
4.  Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project 
NeuroImage  2013;80:80-104.
The human connectome project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the temporal fluctuations in an fMRI time series to deduce ‘functional connectivity’; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3 Tesla, leading to whole brain coverage with 2 mm isotropic resolution in 0.7 second for fMRI, and 1.25 mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7 Tesla magnetic field are also presented, targeting higher resolution, specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields and power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure.
doi:10.1016/j.neuroimage.2013.05.012
PMCID: PMC3740184  PMID: 23702417
5.  Spatially constrained hierarchical parcellation of the brain with resting-state fMRI 
NeuroImage  2013;76:313-324.
We propose a novel computational strategy to partition the cerebral cortex into disjoint, spatially contiguous and functionally homogeneous parcels. The approach exploits spatial dependency in the fluctuations observed with functional Magnetic Resonance Imaging (fMRI) during rest. Single subject parcellations are derived in a two stage procedure in which a set of (~1000 to 5000) stable seeds is grown into an initial detailed parcellation. This parcellation is then further clustered using a hierarchical approach that enforces spatial contiguity of the parcels.
A major challenge is the objective evaluation and comparison of different parcellation strategies; here, we use a range of different measures. Our single subject approach allows a subject-specific parcellation of the cortex, which shows high scan-to-scan reproducibility and whose borders delineate clear changes in functional connectivity. Another important measure, on which our approach performs well, is the overlap of parcels with task fMRI derived clusters. Connectivity-derived parcellation borders are less well matched to borders derived from cortical myelination and from cytoarchitectonic atlases, but this may reflect inherent differences in the data.
doi:10.1016/j.neuroimage.2013.03.024
PMCID: PMC3758955  PMID: 23523803
Resting state fMRI; Cortical parcellation; Connectomics
6.  Imaging human connectomes at the macroscale 
Nature methods  2013;10(6):524-539.
At macroscopic scales, the human connectome is composed of anatomically distinct brain areas, the structural pathways connecting them, and their functional interactions. Successful annotation of phenotypic associations with variation in the connectome and cataloguing of neurophenotypes promise to transform our understanding of the human brain. This review provides a survey of magnetic resonance imaging-based measurements of functional and structural connectivity. We highlight emerging areas of development and inquiry, and emphasize the importance of integrating structural and functional perspectives on brain architecture.
doi:10.1038/nmeth.2482
PMCID: PMC4096321  PMID: 23722212
7.  THE TOPOGRAPHIC CONNECTOME 
Current opinion in neurobiology  2013;23(2):207-215.
Central to macro-connectomics and much of systems neuroscience is the idea that we can summarise macroscopic brain connectivity using a network of “nodes” and “edges” – functionally distinct brain regions and the connections between them. This is an approach that allows a deep understanding of brain dynamics and how they relate to brain circuitry. This approach, however, ignores key features of anatomical connections, such as spatial arrangement and topographic mappings. In this article, we suggest an alternative to this paradigm. We propose that connection topographies can inform us about brain networks in ways that are complementary to the concepts of “nodes” and “edges”. We also show that current neuroimaging technology is capable of revealing details of connection topographies in vivo. These advances, we hope, will allow us to explore brain connectivity in novel ways in the immediate future.
doi:10.1016/j.conb.2012.12.004
PMCID: PMC3622846  PMID: 23298689
8.  The Organization of Dorsal Frontal Cortex in Humans and Macaques 
The Journal of Neuroscience  2013;33(30):12255-12274.
The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed.
doi:10.1523/JNEUROSCI.5108-12.2013
PMCID: PMC3744647  PMID: 23884933
9.  Motor Skill Learning Induces Changes in White Matter Microstructure and Myelination 
The Journal of Neuroscience  2013;33(50):19499-19503.
Learning a novel motor skill is associated with well characterized structural and functional plasticity in the rodent motor cortex. Furthermore, neuroimaging studies of visuomotor learning in humans have suggested that structural plasticity can occur in white matter (WM), but the biological basis for such changes is unclear. We assessed the influence of motor skill learning on WM structure within sensorimotor cortex using both diffusion MRI fractional anisotropy (FA) and quantitative immunohistochemistry. Seventy-two adult (male) rats were randomly assigned to one of three conditions (skilled reaching, unskilled reaching, and caged control). After 11 d of training, postmortem diffusion MRI revealed significantly higher FA in the skilled reaching group compared with the control groups, specifically in the WM subjacent to the sensorimotor cortex contralateral to the trained limb. In addition, within the skilled reaching group, FA across widespread regions of WM in the contralateral hemisphere correlated significantly with learning rate. Immunohistological analysis conducted on a subset of 24 animals (eight per group) revealed significantly increased myelin staining in the WM underlying motor cortex in the hemisphere contralateral (but not ipsilateral) to the trained limb for the skilled learning group versus the control groups. Within the trained hemisphere (but not the untrained hemisphere), myelin staining density correlated significantly with learning rate. Our results suggest that learning a novel motor skill induces structural change in task-relevant WM pathways and that these changes may in part reflect learning-related increases in myelination.
doi:10.1523/JNEUROSCI.3048-13.2013
PMCID: PMC3858622  PMID: 24336716
10.  Model-based analysis of multi-shell diffusion MR data for tractography: How to get over fitting problems 
In this article, we highlight an issue that arises when using multiple b-values in a model-based analysis of diffusion MR data for tractography. The non-mono-exponential decay, commonly observed in experimental data, is shown to induce over-fitting in the distribution of fibre orientations when not considered in the model. Extra fibre orientations perpendicular to the main orientation arise to compensate for the slower apparent signal decay at higher b-values. We propose a simple extension to the ball and stick model based on a continuous Gamma distribution of diffusivities, which significantly improves the fitting and reduces the over-fitting. Using in-vivo experimental data, we show that this model outperforms a simpler, noise floor model, especially at the interfaces between brain tissues, suggesting that partial volume effects are a major cause of the observed non-mono-exponential decay. This model may be helpful for future data acquisition strategies that may attempt to combine multiple shells to improve estimates of fibre orientations in white matter and near the cortex.
doi:10.1002/mrm.24204
PMCID: PMC3359399  PMID: 22334356
11.  Brain Systems for Probabilistic and Dynamic Prediction: Computational Specificity and Integration 
PLoS Biology  2013;11(9):e1001662.
Using computational modelling and neuroimaging, two distinct brain systems are shown to use distinct algorithms to make parallel predictions about the environment. The predictions are then optimally combined to control behavior.
A computational approach to functional specialization suggests that brain systems can be characterized in terms of the types of computations they perform, rather than their sensory or behavioral domains. We contrasted the neural systems associated with two computationally distinct forms of predictive model: a reinforcement-learning model of the environment obtained through experience with discrete events, and continuous dynamic forward modeling. By manipulating the precision with which each type of prediction could be used, we caused participants to shift computational strategies within a single spatial prediction task. Hence (using fMRI) we showed that activity in two brain systems (typically associated with reward learning and motor control) could be dissociated in terms of the forms of computations that were performed there, even when both systems were used to make parallel predictions of the same event. A region in parietal cortex, which was sensitive to the divergence between the predictions of the models and anatomically connected to both computational networks, is proposed to mediate integration of the two predictive modes to produce a single behavioral output.
Author Summary
To interact effectively with the environment, brains must predict future events based on past and current experience. Predictions associated with different behavioural domains of the brain are often associated with different algorithmic forms. For example, whereas the motor system makes dynamic moment-by-moment predictions based on physical world models, the reward system is more typically associated with statistical predictions learned over discrete events. However, in perceptually rich natural environments, behaviour is not neatly segmented into tasks like “reward learning” and “motor control.” Instead, many different types of information are available in parallel. The brain must both select behaviourally relevant information and arbitrate between conflicting predictions. To investigate how the brain balances and integrates different types of predictive information, we set up a task in which humans predicted an object's flight trajectory by using one of two strategies: either a statistical model (based on where objects had often landed in the past) or dynamic calculation of the current flight trajectory. Using fMRI, we show that brain activity switches between different regions of the brain, depending on which predictive strategy was used, even though behavioural output remained the same. Furthermore, we found that brain regions involved in selecting actions took into account the predictions from both competing algorithms, weighting each algorithm optimally in terms of the precision with which it could predict the event of interest. Thus, these distinct brain systems compete to control predictive behaviour.
doi:10.1371/journal.pbio.1001662
PMCID: PMC3782423  PMID: 24086106
12.  RubiX: Combining Spatial Resolutions for Bayesian Inference of Crossing Fibers in Diffusion MRI 
The trade-off between signal-to-noise ratio (SNR) and spatial specificity governs the choice of spatial resolution in magnetic resonance imaging (MRI); diffusion-weighted (DW) MRI is no exception. Images of lower resolution have higher signal to noise ratio, but also more partial volume artifacts. We present a data-fusion approach for tackling this trade-off by combining DW MRI data acquired both at high and low spatial resolution. We combine all data into a single Bayesian model to estimate the underlying fiber patterns and diffusion parameters. The proposed model, therefore, combines the benefits of each acquisition. We show that fiber crossings at the highest spatial resolution can be inferred more robustly and accurately using such a model compared to a simpler model that operates only on high-resolution data, when both approaches are matched for acquisition time.
doi:10.1109/TMI.2012.2231873
PMCID: PMC3767112  PMID: 23362247
Brain; diffusion-weighted imaging; inverse methods; magnetic resonance imaging (MRI); tractography
13.  Human and monkey ventral prefrontal fibers use the same organizational principles to reach their targets: tracing versus tractography 
This article is a comparative study of white matter projections from ventral prefrontal cortex (vPFC) between human and macaque brains. We test whether the organizational rules that vPFC connections follow in macaques are preserved in humans. These rules concern the trajectories of some of the white matter projections from vPFC, and how the position of regions in the vPFC dictate the trajectories of their projections in the white matter. In order to address this question, we present a novel approach that combines direct tracer measurements of entire white matter trajectories in macaque monkeys with diffusion MRI tractography of both macaques and humans. The approach allows us to provide explicit validation of diffusion tractography and transfer tractography strategies across species to test the extent to which inferences from macaques can be applied to human neuroanatomy. Apart from one exception, we found a remarkable overlap between the two techniques in the macaque. Furthermore the organizational principles followed by vPFC tracts in macaques are preserved in humans.
doi:10.1523/JNEUROSCI.2457-12.2013
PMCID: PMC3602794  PMID: 23407972
14.  Tractography - where do we go from here? 
Brain connectivity  2011;1(3):169-183.
Diffusion tractography offers enormous potential for the study of human brain anatomy. However, as a method to study brain connectivity, tractography suffers from limitations, as it is indirect, inaccurate, and difficult to quantify. Despite these limitations, appropriate use of tractography can be a powerful means to address certain questions. In addition, while some of tractography’s limitations are fundamental, others could be alleviated by methodological and technological advances. This article provides an overview of diffusion MR tractography methods with a focus on how future advances might address challenges in measuring brain connectivity. Parts of this review are somewhat provocative, in the hope that they may trigger discussions possibly lacking in a field where the apparent simplicity of the methods (compared to their FMRI counterparts) can hide some fundamental issues that ultimately hinder the interpretation of findings, and cast doubt as to what tractography can really teach us about human brain anatomy.
doi:10.1089/brain.2011.0033
PMCID: PMC3677805  PMID: 22433046
15.  Relating Brain Damage to Brain Plasticity in Patients With Multiple Sclerosis 
Background
Failure of adaptive plasticity with increasing pathology is suggested to contribute to progression of disability in multiple sclerosis (MS). However, functional impairments can be reduced with practice, suggesting that brain plasticity is preserved even in patients with substantial damage.
Objective
Here, functional magnetic resonance imaging (fMRI) was used to probe systems-level mechanisms of brain plasticity associated with improvements in visuomotor performance in MS patients and related to measures of microstructural damage.
Methods
23 MS patients and 12 healthy controls underwent brain fMRI during the first practice session of a visuomotor task (short-term practice) and after 2 weeks of daily practice with the same task (longer-term practice). Participants also underwent a structural brain MRI scan.
Results
Patients performed more poorly than controls at baseline. Nonetheless, with practice, patients showed performance improvements similar to controls and independent of the extent of MRI measures of brain pathology. Different relationships between performance improvements and activations were found between groups: greater short-term improvements were associated with lower activation in the sensorimotor, posterior cingulate, and parahippocampal cortices for patients, whereas greater long-term improvements correlated with smaller activation reductions in the visual cortex of controls.
Conclusions
Brain plasticity for visuomotor practice is preserved in MS patients despite a high burden of cerebral pathology. Cognitive systems different from those acting in controls contribute to this plasticity in patients. These findings challenge the notion that increasing pathology is accompanied by an outright failure of adaptive plasticity, supporting a neuroscientific rationale for recovery-oriented strategies even in chronically disabled patients.
doi:10.1177/1545968311433208
PMCID: PMC3674542  PMID: 22328685
16.  Structural and Functional Bases for Individual Differences in Motor Learning 
Human brain mapping  2011;32(3):494-508.
People vary in their ability to learn new motor skills. We hypothesize that between-subject variability in brain structure and function can explain differences in learning. We use brain functional and structural MRI methods to characterize such neural correlates of individual variations in motor learning. Healthy subjects applied isometric grip force of varying magnitudes with their right hands cued visually to generate smoothly-varying pressures following a regular pattern. We tested whether individual variations in motor learning were associated with anatomically colocalized variations in magnitude of functional MRI (fMRI) signal or in MRI differences related to white and grey matter microstructure. We found that individual motor learning was correlated with greater functional activation in the prefrontal, premotor, and parietal cortices, as well as in the basal ganglia and cerebellum.
Structural MRI correlates were found in the premotor cortex [for fractional anisotropy (FA)] and in the cerebellum [for both grey matter density and FA]. The cerebellar microstructural differences were anatomically colocalized with fMRI correlates of learning. This study thus suggests that variations across the population in the function and structure of specific brain regions for motor control explain some of the individual differences in skill learning. This strengthens the notion that brain structure determines some limits to cognitive function even in a healthy population. Along with evidence from pathology suggesting a role for these regions in spontaneous motor recovery, our results also highlight potential targets for therapeutic interventions designed to maximize plasticity for recovery of similar visuomotor skills after brain injury.
doi:10.1002/hbm.21037
PMCID: PMC3674543  PMID: 20533562
17.  Preservation of motor skill learning in patients with multiple sclerosis 
Background
Several studies have demonstrated benefits of rehabilitation in multiple sclerosis (MS). However, the neuroscientific foundations for rehabilitation in MS are poorly established.
Objectives
As rehabilitation and motor learning share similar mechanisms of brain plasticity, we test whether the dynamics of skill learning are preserved in MS patients relative to controls.
Methods
MS patients and controls learned a repeating sequence of hand movements and were assessed for short-term learning. Long-term learning was tested in another cohort of patients and controls practising the same sequence daily for two weeks.
Results
Despite differences in baseline performance, the dynamics and extent of improvements were comparable between MS and control groups for both the short- and long-term learning. Even the most severely damaged patients were capable of performance improvements of similar magnitude to that seen in controls. After one week of training patients performed as well as the controls at baseline.
Conclusions
Mechanisms for short- and long-term plasticity may compensate for impaired functional connectivity in MS to mediate behavioural improvements. Future studies are needed to define the neurobiological substrates of this plasticity and the extent to which mechanisms of plasticity in patients may be distinct from those used for motor learning in controls.
doi:10.1177/1352458510381257
PMCID: PMC3671324  PMID: 20834040
18.  Ball and Rackets: Inferring Fibre Fanning from Diffusion-weighted MRI 
Neuroimage  2012;60(2):1412-1425.
A number of methods have been proposed for resolving crossing fibres from diffusion-weighted (DW) MRI. However, other complex fibre geometries have drawn minimal attention. In this study, we focus on fibre orientation dispersion induced by within-voxel fanning. We use a multi- compartment, model-based approach to estimate fibre dispersion. Bingham distributions are employed to represent continuous distributions of fibre orientations, centred around a main orientation, and capturing anisotropic dispersion. We evaluate the accuracy of the model for different simulated fanning geometries, under different acquisition protocols and we illustrate the high SNR and angular resolution needs. We also perform a qualitative comparison between our parametric approach and five popular non-parametric techniques that are based on orientation distribution functions (ODFs). This comparison illustrates how the same underlying geometry can be depicted by different methods. We apply the proposed model on high-quality, post-mortem macaque data and present whole-brain maps of fibre dispersion, as well as exquisite details on the local anatomy of fibre distributions in various white matter regions.
doi:10.1016/j.neuroimage.2012.01.056
PMCID: PMC3304013  PMID: 22270351
Diffusion MRI; white matter; parametric deconvolution; fibre fanning; fibre bending; Bingham distribution; macaque
19.  A Brain Network Processing the Age of Faces 
PLoS ONE  2012;7(11):e49451.
Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.
doi:10.1371/journal.pone.0049451
PMCID: PMC3502502  PMID: 23185334
20.  Diffusion tractography of post-mortem human brains: Optimization and comparison of spin echo and steady-state free precession techniques 
Neuroimage  2012;59(3-2):2284-2297.
Diffusion imaging of post-mortem brains could provide valuable data for validation of diffusion tractography of white matter pathways. Long scans (e.g., overnight) may also enable high-resolution diffusion images for visualization of fine structures. However, alterations to post-mortem tissue (T2 and diffusion coefficient) present significant challenges to diffusion imaging with conventional diffusion-weighted spin echo (DW-SE) acquisitions, particularly for imaging human brains on clinical scanners. Diffusion-weighted steady-state free precession (DW-SSFP) has been proposed as an alternative acquisition technique to ameliorate this tradeoff in large-bore clinical scanners. In this study, both DWSE and DW-SSFP are optimized for use in fixed white matter on a clinical 3-Tesla scanner. Signal calculations predict superior performance from DW-SSFP across a broad range of protocols and conditions. DW-SE and DW-SSFP data in a whole, post-mortem human brain are compared for 6- and 12-hour scan durations. Tractography is performed in major projection, commissural and association tracts (corticospinal tract, corpus callosum, superior longitudinal fasciculus and cingulum bundle). The results demonstrate superior tract-tracing from DW-SSFP data, with 6-hour DW-SSFP data performing as well as or better than 12-hour DW-SE scans. These results suggest that DW-SSFP may be a preferred method for diffusion imaging of post-mortem human brains. The ability to estimate multiple fibers in imaging voxels is also demonstrated, again with greater success in DW-SSFP data.
Highlights
► Comparison of DW-SE and DW-SSFP for post-mortem imaging on clinical scanners. ► Optimization of protocols predicts 50-130% higher SNR efficiency in DW-SSFP. ► Comparison of tractography 6- and 12-hour DW-SE and DW-SSFP scans. ► Lower uncertainty on fibre direction in DW-SSFP produces superior tractography. ► Crossing fibres can be estimated from 12-hour DW-SSFP data.
doi:10.1016/j.neuroimage.2011.09.054
PMCID: PMC3314951  PMID: 22008372
Diffusion; Tractography; Post mortem; Steady-state free precession; DTI
21.  DIFFUSION-WEIGHTED IMAGING TRACTOGRAPHY-BASED PARCELLATION OF THE HUMAN PARIETAL CORTEX AND COMPARISON WITH HUMAN AND MACAQUE RESTING STATE FUNCTIONAL CONNECTIVITY 
Despite the prominence of parietal activity in human neuromaging investigations of sensorimotor and cognitive processes there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI) based tractography and functional interactions were assessed by correlations in activity measured with functional MRI (fMRI) at rest. Resting state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into ten component clusters. The resting state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex.
doi:10.1523/JNEUROSCI.5102-10.2011
PMCID: PMC3091022  PMID: 21411650
AIP; MIP; LIP; VIP; IPL; SPL
22.  Diffusion imaging of whole, post-mortem human brains on a clinical MRI scanner 
Neuroimage  2011;57(1-4):167-181.
Diffusion imaging of post mortem brains has great potential both as a reference for brain specimens that undergo sectioning, and as a link between in vivo diffusion studies and “gold standard” histology/dissection. While there is a relatively mature literature on post mortem diffusion imaging of animals, human brains have proven more challenging due to their incompatibility with high-performance scanners. This study presents a method for post mortem diffusion imaging of whole, human brains using a clinical 3-Tesla scanner with a 3D segmented EPI spin-echo sequence. Results in eleven brains at 0.94 × 0.94 × 0.94 mm resolution are presented, and in a single brain at 0.73 × 0.73 × 0.73 mm resolution. Region-of-interest analysis of diffusion tensor parameters indicate that these properties are altered compared to in vivo (reduced diffusivity and anisotropy), with significant dependence on post mortem interval (time from death to fixation). Despite these alterations, diffusion tractography of several major tracts is successfully demonstrated at both resolutions. We also report novel findings of cortical anisotropy and partial volume effects.
Research highlights
► Acquisition and processing protocols for diffusion MRI of post-mortem human brains. ► Effect of post-mortem and scan intervals on diffusion indices. ► Tractography in post-mortem human brains. ► Radial diffusion anisotropy in cortical gray matter.
doi:10.1016/j.neuroimage.2011.03.070
PMCID: PMC3115068  PMID: 21473920
Diffusion tensor imaging; Tractography; Post mortem; Human; Brain
23.  Automated Probabilistic Reconstruction of White-Matter Pathways in Health and Disease Using an Atlas of the Underlying Anatomy 
We have developed a method for automated probabilistic reconstruction of a set of major white-matter pathways from diffusion-weighted MR images. Our method is called TRACULA (TRActs Constrained by UnderLying Anatomy) and utilizes prior information on the anatomy of the pathways from a set of training subjects. By incorporating this prior knowledge in the reconstruction procedure, our method obviates the need for manual interaction with the tract solutions at a later stage and thus facilitates the application of tractography to large studies. In this paper we illustrate the application of the method on data from a schizophrenia study and investigate whether the inclusion of both patients and healthy subjects in the training set affects our ability to reconstruct the pathways reliably. We show that, since our method does not constrain the exact spatial location or shape of the pathways but only their trajectory relative to the surrounding anatomical structures, a set a of healthy training subjects can be used to reconstruct the pathways accurately in patients as well as in controls.
doi:10.3389/fninf.2011.00023
PMCID: PMC3193073  PMID: 22016733
tractography; diffusion MRI; white matter
24.  Continuity, Divergence, and the Evolution of Brain Language Pathways 
Recently, the assumption of evolutionary continuity between humans and non-human primates has been used to bolster the hypothesis that human language is mediated especially by the ventral extreme capsule pathway that mediates auditory object recognition in macaques. Here, we argue for the importance of evolutionary divergence in understanding brain language evolution. We present new comparative data reinforcing our previous conclusion that the dorsal arcuate fasciculus pathway was more significantly modified than the ventral extreme capsule pathway in human evolution. Twenty-six adult human and twenty-six adult chimpanzees were imaged with diffusion-weighted MRI and probabilistic tractography was used to track and compare the dorsal and ventral language pathways. Based on these and other data, we argue that the arcuate fasciculus is likely to be the pathway most essential for higher-order aspects of human language such as syntax and lexical–semantics.
doi:10.3389/fnevo.2011.00011
PMCID: PMC3249609  PMID: 22319495
language; evolution; brain; chimpanzee; arcuate fasciculus; extreme capsule
25.  Preoperative estimation of residual volume for WHO grade II glioma resected with intraoperative functional mapping 
Neuro-Oncology  2007;9(1):63-69.
Despite the lack of class I evidence, it is widely agreed that surgery can improve the functional and vital prognosis for WHO grade II gliomas when the resection is at least subtotal radiologically, that is, leaving less than 10 cm3 of visible residual tumor. Because these tumors frequently invade functional areas, the preoperative estimation of the probable residual volume remains challenging. This article presents a probabilistic map of postoperative residues, with the aim of predicting before the decision for surgical intervention whether the resection could be subtotal. We selected 65 patients who underwent surgery with intraoperative functional mapping between 1999 and 2004 for a WHO grade II glioma located in a sensorimotor and/or language area. For each case, the postoperative image was normalized on a standard atlas, and the residual tumor was segmented. A probabilistic map of residues was then computed. The fusion between the map and a preoperative image allowed a preoperative estimation of the expected extent of resection. The map enhances the regions where grade II glioma cannot be resected. The success rate for the preoperative classification of partial versus subtotal resection is 82%. Although both its reliability and accuracy have to be improved, this probabilistic map gives preoperatively an objective estimation of the expected extent of resection for grade II glioma resected under intraoperative functional mapping. This rationale will assist in decisions regarding surgical resection and may thus contribute to the elaboration of a therapeutic consensus for WHO grade II glioma.
doi:10.1215/15228517-2006-015
PMCID: PMC1828101  PMID: 17018698
grade II glioma; intraoperative mapping; probabilistic map

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