Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Long-term musical training induces white matter plasticity in emotion and language networks.

Numerous studies have reported that long-term musical training can affect brain functionality and induce structural alterations in the brain. Singing is a form of vocal musical expression with an unparalleled capacity for communicating emotion; however, there has been relatively little research on neuroplasticity at the network level in vocalists (i.e., noninstrumental musicians). Our objective in this study was to elucidate changes in the neural network architecture following long-term training in the musical arts. We employed a framework based on graph theory to depict the connectivity and efficiency of structural networks in the brain, based on diffusion-weighted images obtained from 35 vocalists, 27 pianists, and 33 nonmusicians. Our results revealed that musical training (both voice and piano) could enhance connectivity among emotion-related regions of the brain, such as the amygdala. We also discovered that voice training reshaped the architecture of experience-dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. It appears that vocal-related changes in areas such as the insula, paracentral lobule, supramarginal gyrus, and putamen are associated with functional segregation, multisensory integration, and enhanced network interconnectivity. These results suggest that long-term musical training can strengthen or prune white matter connectivity networks in an experience-dependent manner.

Performance of orientation distribution function-fingerprinting with a biophysical multicompartment diffusion model.

PURPOSE: Orientation Distribution Function (ODF) peak finding methods typically fail to reconstruct fibers crossing at shallow angles below 40°, leading to errors in tractography. ODF-Fingerprinting (ODF-FP) with the biophysical multicompartment diffusion model allows for breaking this barrier. METHODS: A randomized mechanism to generate a multidimensional ODF-dictionary that covers biologically plausible ranges of intra- and extra-axonal diffusivities and fraction volumes is introduced. This enables ODF-FP to address the high variability of brain tissue. The performance of the proposed approach is evaluated on both numerical simulations and a reconstruction of major fascicles from high- and low-resolution in vivo diffusion images. RESULTS: ODF-FP with the suggested modifications correctly identifies fibers crossing at angles as shallow as 10 degrees in the simulated data. In vivo, our approach reaches 56% of true positives in determining fiber directions, resulting in visibly more accurate reconstruction of pyramidal tracts, arcuate fasciculus, and optic radiations than the state-of-the-art techniques. Moreover, the estimated diffusivity values and fraction volumes in corpus callosum conform with the values reported in the literature. CONCLUSION: The modified ODF-FP outperforms commonly used fiber reconstruction methods at shallow angles, which improves deterministic tractography outcomes of major fascicles. In addition, the proposed approach allows for linearization of the microstructure parameters fitting problem.

Mapping brain-behavior networks using functional and structural connectome fingerprinting in the HCP dataset.

INTRODUCTION: Connectome analysis of the human brain's structural and functional architecture provides a unique opportunity to understand the organization of the brain's functional architecture. In previous studies, connectome fingerprinting using brain functional connectivity profiles as an individualized trait was able to predict an individual's neurocognitive performance from the Human Connectome Project (HCP) neurocognitive datasets. MATERIALS AND METHODS: In the present study, we extend connectome fingerprinting from functional connectivity (FC) to structural connectivity (SC), identifying multiple relationships between behavioral traits and brain connectivity. Higher-order neurocognitive tasks were found to have a weaker association with structural connectivity than its functional connectivity counterparts. RESULTS: Neurocognitive tasks with a higher sensory footprint were, however, found to have a stronger association with structural connectivity than their functional connectivity counterparts. Language behavioral measurements had a particularly stronger correlation, especially between performance on the picture language test (Pic Vocab) and both FC (r = .28, p < .003) and SC (r = 0.27, p < .00077). CONCLUSIONS: At the neural level, we found that the pattern of structural brain connectivity related to high-level language performance is consistent with the language white matter regions identified in presurgical mapping. We illustrate how this approach can be used to generalize the connectome fingerprinting framework to structural connectivity and how this can help understand the connections between cognitive behavior and the white matter connectome of the brain.

Author Correction: The challenge of mapping the human connectome based on diffusion tractography.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fingerprinting Orientation Distribution Functions in diffusion MRI detects smaller crossing angles.

Diffusion tractography is routinely used to study white matter architecture and brain connectivity in vivo. A key step for successful tractography of neuronal tracts is the correct identification of tract directions in each voxel. Here we propose a fingerprinting-based methodology to identify these fiber directions in Orientation Distribution Functions, dubbed ODF-Fingerprinting (ODF-FP). In ODF-FP, fiber configurations are selected based on the similarity between measured ODFs and elements in a pre-computed library. In noisy ODFs, the library matching algorithm penalizes the more complex fiber configurations. ODF simulations and analysis of bootstrapped partial and whole-brain in vivo datasets show that the ODF-FP approach improves the detection of fiber pairs with small crossing angles while maintaining fiber direction precision, which leads to better tractography results. Rather than focusing on the ODF maxima, the ODF-FP approach uses the whole ODF shape to infer fiber directions to improve the detection of fiber bundles with small crossing angle. The resulting fiber directions aid tractography algorithms in accurately displaying neuronal tracts and calculating brain connectivity.

Low Rank plus Sparse decomposition of ODFs for improved detection of group-level differences and variable correlations in white matter.

A novel approach is presented for group statistical analysis of diffusion weighted MRI datasets through voxelwise Orientation Distribution Functions (ODF). Recent advances in MRI acquisition make it possible to use high quality diffusion weighted protocols (multi-shell, large number of gradient directions) for routine in vivo study of white matter architecture. The dimensionality of these data sets is however often reduced to simplify statistical analysis. While these approaches may detect large group differences, they do not fully capitalize on all acquired image volumes. Incorporation of all available diffusion information in the analysis however risks biasing the outcome by outliers. Here we propose a statistical analysis method operating on the ODF, either the diffusion ODF or fiber ODF. To avoid outlier bias and reliably detect voxelwise group differences and correlations with demographic or behavioral variables, we apply the Low-Rank plus Sparse (L+S) matrix decomposition on the voxelwise ODFs which separates the sparse individual variability in the sparse matrix S whilst recovering the essential ODF features in the low-rank matrix L. We demonstrate the performance of this ODF L+S approach by replicating the established negative association between global white matter integrity and physical obesity in the Human Connectome dataset. The volume of positive findings p<0.01,227cm3, agrees with and expands on the volume found by TBSS (17 cm3), Connectivity based fixel enhancement (15 cm3) and Connectometry (212 cm3). In the same dataset we further localize the correlations of brain structure with neurocognitive measures such as fluid intelligence and episodic memory. The presented ODF L+S approach will aid in the full utilization of all acquired diffusion weightings leading to the detection of smaller group differences in clinically relevant settings as well as in neuroscience applications.

The challenge of mapping the human connectome based on diffusion tractography.

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.

Multicontrast MRI Quantification of Focal Inflammation and Degeneration in Multiple Sclerosis.

INTRODUCTION: Local microstructural pathology in multiple sclerosis patients might influence their clinical performance. This study applied multicontrast MRI to quantify inflammation and neurodegeneration in MS lesions. We explored the impact of MRI-based lesion pathology in cognition and disability. METHODS: 36 relapsing-remitting MS subjects and 18 healthy controls underwent neurological, cognitive, behavioural examinations and 3 T MRI including (i) fluid attenuated inversion recovery, double inversion recovery, and magnetization-prepared gradient echo for lesion count; (ii) T1, T2, and T2(*) relaxometry and magnetisation transfer imaging for lesion tissue characterization. Lesions were classified according to the extent of inflammation/neurodegeneration. A generalized linear model assessed the contribution of lesion groups to clinical performances. RESULTS: Four lesion groups were identified and characterized by (1) absence of significant alterations, (2) prevalent inflammation, (3) concomitant inflammation and microdegeneration, and (4) prevalent tissue loss. Groups 1, 3, 4 correlated with general disability (Adj-R (2) = 0.6; P = 0.0005), executive function (Adj-R (2) = 0.5; P = 0.004), verbal memory (Adj-R (2) = 0.4; P = 0.02), and attention (Adj-R (2) = 0.5; P = 0.002). CONCLUSION: Multicontrast MRI provides a new approach to infer in vivo histopathology of plaques. Our results support evidence that neurodegeneration is the major determinant of patients' disability and cognitive dysfunction.

Quantitative Analysis of Myelin and Axonal Remodeling in the Uninjured Motor Network After Stroke.

Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether poststroke connectivity remodeling depends on axonal and/or myelin changes. Diffusion-spectrum imaging and magnetization transfer MRI at 3T were performed in 10 patients in acute phase, at 1 and 6 months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender-matched healthy volunteers were scanned 1 month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to magnetic resonance imaging (MRI). In the contralesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR were performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation, and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke.

Multicontrast connectometry: a new tool to assess cerebellum alterations in early relapsing-remitting multiple sclerosis.

BACKGROUND: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. METHODS: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. RESULTS: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. CONCLUSION: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage.

Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis.

INTRODUCTION: In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) provides only limited insights into the nature of brain damage with modest clinic-radiological correlation. In this study, we applied recent advances in MRI techniques to study brain microstructural alterations in early relapsing-remitting MS (RRMS) patients with minor deficits. Further, we investigated the potential use of advanced MRI to predict functional performances in these patients. METHODS: Brain relaxometry (T1, T2, T2*) and magnetization transfer MRI were performed at 3T in 36 RRMS patients and 18 healthy controls (HC). Multicontrast analysis was used to assess for microstructural alterations in normal-appearing (NA) tissue and lesions. A generalized linear model was computed to predict clinical performance in patients using multicontrast MRI data, conventional MRI measures as well as demographic and behavioral data as covariates. RESULTS: Quantitative T2 and T2* relaxometry were significantly increased in temporal normal-appearing white matter (NAWM) of patients compared to HC, indicating subtle microedema (P = 0.03 and 0.004). Furthermore, significant T1 and magnetization transfer ratio (MTR) variations in lesions (mean T1 z-score: 4.42 and mean MTR z-score: -4.09) suggested substantial tissue loss. Combinations of multicontrast and conventional MRI data significantly predicted cognitive fatigue (P = 0.01, Adj-R (2) = 0.4), attention (P = 0.0005, Adj-R (2) = 0.6), and disability (P = 0.03, Adj-R (2) = 0.4). CONCLUSION: Advanced MRI techniques at 3T, unraveled the nature of brain tissue damage in early MS and substantially improved clinical-radiological correlations in patients with minor deficits, as compared to conventional measures of disease.

Quantitative comparison of reconstruction methods for intra-voxel fiber recovery from diffusion MRI.

Validation is arguably the bottleneck in the diffusion magnetic resonance imaging (MRI) community. This paper evaluates and compares 20 algorithms for recovering the local intra-voxel fiber structure from diffusion MRI data and is based on the results of the "HARDI reconstruction challenge" organized in the context of the "ISBI 2012" conference. Evaluated methods encompass a mixture of classical techniques well known in the literature such as diffusion tensor, Q-Ball and diffusion spectrum imaging, algorithms inspired by the recent theory of compressed sensing and also brand new approaches proposed for the first time at this contest. To quantitatively compare the methods under controlled conditions, two datasets with known ground-truth were synthetically generated and two main criteria were used to evaluate the quality of the reconstructions in every voxel: correct assessment of the number of fiber populations and angular accuracy in their orientation. This comparative study investigates the behavior of every algorithm with varying experimental conditions and highlights strengths and weaknesses of each approach. This information can be useful not only for enhancing current algorithms and develop the next generation of reconstruction methods, but also to assist physicians in the choice of the most adequate technique for their studies.

Impaired frontal synchronization of spontaneous magnetoencephalographic activity in patients with bipolar disorder.

Recent functional imaging studies demonstrated that brain exhibit coherent, synchronized activities during resting state and the dynamics may be impaired in various psychiatric illnesses. In order to investigate the change of neural dynamics in bipolar disorder, we used a new nonlinear measurement "similarity index" to analyze the magnetoencephalography (MEG) recordings and test the hypothesis that there are synchronization changes within different frequency bands in the frontal cortex of patients with bipolar disorder. Ten patients with bipolar I disorder during euthymic phase and ten normal controls underwent 2min eye-closed resting recording with a whole-head 306-channel MEG system. Eleven channels of MEG data from frontal area were selected for analysis. Synchronization level in the delta (2-4Hz), theta (4-8Hz), alpha (8-12Hz) and beta (12-24Hz) bands was calculated for each subject and compared across group. The results showed that significant dynamic changes in bipolar patients can be characterized by increased synchronization of slow frequency oscillations (delta) and decreased synchronization of fast frequency oscillations (beta). Furthermore, the positive correlation between beta synchronization level and preservative errors in Wisconcin card sorting task was found which would implicate the deficit of executive function in bipolar patients. Our findings indicate that analysis of spontaneous MEG recordings at resting state using nonlinear dynamic approaches may disclose the subtle regional changes of neural dynamics in BD.