Jennifer S. W. Campbell

Dissociating the Human Language Pathways with High Angular Resolution Diffusion Fiber Tractography

The anatomical connectivity of ventrolateral frontal areas 44 and 45, which in the human brain constitute Brocas region, has been revisited on the basis of experimental anatomical tracer evidence in the nonhuman primate that the homologues of areas 44 and 45 have distinct bidirectional corticocortical connections. Here we show, using high angular resolution diffusion imaging in the living human brain, a dissociation between the specific projections from the pars opercularis (area 44) and the pars triangularis (area 45) in the ventrolateral frontal lobe. As in the macaque monkey, area 44 has distinct connections with the rostral inferior parietal lobule via the third branch of the superior longitudinal fasciculus. In contrast, area 45 connects with the superior temporal gyrus, anterior to Heschls gyrus, via the extreme capsule fiber system. These results highlight the differences in connectivity between areas 44 and 45 which had previously been thought to be uniformly connected with the posterior temporal region via the arcuate fasciculus. We also provide evidence in the human brain that the arcuate fasciculus, as in the macaque monkey brain, connects the posterior superior temporal region with dorsolateral frontal areas 8 and rostral 6 that lie above areas 44 and 45. Thus, monkey and human evidence suggests that the connections of areas 44 and 45 are much more differentiated than had previously been thought and provide the basis for studies searching for their differential contribution in function.

Flow-based fiber tracking with diffusion tensor and q-ball data: Validation and comparison to principal diffusion direction techniques

In this study, we evaluate the performance of a flow-based surface evolution fiber tracking algorithm by means of a physical anisotropic diffusion phantom with known connectivity. We introduce a novel speed function for surface evolution that is derived from either diffusion tensor (DT) data, high angular resolution diffusion (HARD) data, or a combined DT-HARD hybrid approach. We use the model-free q-ball imaging (QBI) approach for HARD reconstruction. The anisotropic diffusion phantom allows us to compare and evaluate the performance of different fiber tracking approaches in the presence of real imaging artifacts, noise, and subvoxel partial volume averaging of fiber directions. The surface evolution approach, using the full diffusion tensor as opposed to the principal diffusion direction (PDD) only, is compared to PDD-based line propagation fiber tracking. Additionally, DT reconstruction is compared to HARD reconstruction for fiber tracking, both using surface evolution. We show the potential for surface evolution using the full diffusion tensor to map connections in regions of subvoxel partial volume averaging of fiber directions, which can be difficult to map with PDD-based methods. We then show that the fiber tracking results can be improved by using high angular resolution reconstruction of the diffusion orientation distribution function in cases where the diffusion tensor model fits the data poorly.

In vivo histology of the myelin g-ratio with magnetic resonance imaging

The myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, is a fundamental property of white matter that can be computed from a simple formula relating the myelin volume fraction to the fiber volume fraction or the axon volume fraction. In this paper, a unique combination of magnetization transfer, diffusion imaging and histology is presented, providing a novel method for in vivo magnetic resonance imaging of the axon volume fraction and the myelin g-ratio. Our method was demonstrated in the corpus callosum of one cynomolgus macaque, and applied to obtain full-brain g-ratio maps in one healthy human subject and one multiple sclerosis patient. In the macaque, the g-ratio was relatively constant across the corpus callosum, as measured by both MRI and electron microscopy. In the human subjects, the g-ratio in multiple sclerosis lesions was higher than in normal appearing white matter, which was in turn higher than in healthy white matter. Measuring the g-ratio brings us one step closer to fully characterizing white matter non-invasively, making it possible to perform in vivo histology of the human brain during development, aging, disease and treatment.

Mathematical methods for diffusion MRI processing

In this article, we review recent mathematical models and computational methods for the processing of diffusion Magnetic Resonance Images, including state-of-the-art reconstruction of diffusion models, cerebral white matter connectivity analysis, and segmentation techniques. We focus on Diffusion Tensor Images (DTI) and Q-Ball Images (QBI).

Labeling of ambiguous subvoxel fibre bundle configurations in high angular resolution diffusion MRI

Whereas high angular resolution reconstruction methods for diffusion MRI can estimate multiple dominant fibre orientations within a single imaging voxel, they are fundamentally limited in certain cases of complex subvoxel fibre structures, resulting in ambiguous local orientation distribution functions. In this article we address the important problem of disambiguating such complex subvoxel fibre tract configurations, with the purpose of improving the performance of fibre tractography. We do so by extending a curve inference method to distinguish between the cases of curving and fanning fibre bundles using differential geometric estimates in a local neighbourhood. The key benefit of this method is the inference of curves, instead of only fibre orientations, to model the underlying fibre bundles. This in turn allows distinct fibre geometries that contain nearly identical sets of fibre orientations at a voxel, to be distinguished from one another. Experimental results demonstrate the ability of the method to successfully label voxels into one of the above categories and improve the performance of a fibre-tracking algorithm.

Fronto-temporal disconnectivity and clinical short-term outcome in first episode psychosis: A DTI-tractography study

Determining reliable markers of clinical outcome for psychosis is essential to adjust intervention efforts. White matter alterations exist prior to psychosis onset but its association with clinical outcome in the very early phase of psychosis is currently unknown. In the present study, white matter was assessed by diffusion tensor imaging (DTI) in patients with first episode psychosis (FEP) and healthy controls. Forty-four FEP patients and 30 matched healthy controls completed a DTI scan. The patient group was split in poor (n = 24) and good (n = 20) outcome subgroups based on 6-month clinical data. DTI tractography was used to estimate fractional anisotropy (FA) in the three main tracts connecting frontal and temporal regions (i.e. the cingulum, the superior longitudinal fasciculus and the uncinate fasciculus). The analyses showed selective FA reductions in both the uncinate and the superior longitudinal fasciculi, but not in the cingulum, when comparing FEP patients to healthy controls. FEP subgroup analyses revealed greater white matter changes in these tracts in patients with poor outcome as compared to patients with good outcome. These findings confirm that abnormal fronto-temporal connectivity contributes to the physiopathology of FEP and constitutes an early marker of clinical short-term outcome.

Potential and limitations of diffusion MRI tractography for the study of language

Diffusion magnetic resonance imaging (MRI) is a tremendously promising tool for imaging tissue microstructure, and for inferring large scale structural connectivity in vivo. However, the sensitivity of the technique is highly dependent on methodological details. Acquisition parameters, pre-processing steps, reconstruction models, and statistical analysis all affect the final sensitivity, specificity, and accuracy of a study. In the case of fiber pathway reconstruction in the central nervous system, termed tractography, false positive and false negative results abound, and interpretation of results must take into account the potential shortcomings of the techniques used. This article will review the strengths and limitations of different types of diffusion MRI tractography analysis, and highlight what one can realistically hope to learn from such imaging studies of the human brain.

g-Ratio weighted imaging of the human spinal cord in vivo.

Abstract The fiber g‐ratio is defined as the ratio of the inner to the outer diameter of the myelin sheath. This ratio provides a measure of the myelin thickness that complements axon morphology (diameter and density) for assessment of demyelination in diseases such as multiple sclerosis. Previous work has shown that an aggregate g‐ratio map can be computed using a formula that combines axon and myelin density measured with quantitative MRI. In this work, we computed g‐ratio weighted maps in the cervical spinal cord of nine healthy subjects. We utilized the 300 mT/m gradients from the CONNECTOM scanner to estimate the fraction of restricted water (fr) with high accuracy, using the CHARMED model. Myelin density was estimated using the lipid and macromolecular tissue volume (MTV) method, derived from normalized proton density (PD) mapping. The variability across spinal level, laterality and subject were assessed using a three‐way ANOVA. The average g‐ratio value obtained in the white matter was 0.76+/−0.03, consistent with previous histology work. Coefficients of variation of fr and MTV were respectively 4.3% and 13.7%. fr and myelin density were significantly different across spinal tracts (p=3×10−7 and 0.004 respectively) and were positively correlated in the white matter (r=0.42), suggesting shared microstructural information. The aggregate g‐ratio did not show significant differences across tracts (p=0.6). This study suggests that fr and myelin density can be measured in vivo with high precision and that they can be combined to produce a g‐ratio‐weighted map robust to free water pool contamination from cerebrospinal fluid or veins. Potential applications include the study of early demyelination in multiple sclerosis, and the quantitative assessment of remyelination drugs. Graphical abstract Figure. No caption available.

A geometric flow for white matter fibre tract reconstruction

In magnetic resonance diffusion tensor imaging (DTI), the direction and magnitude of diffusion of water molecules is characterized by a diffusion tensor. In the central nervous system, the highly organized fibre structure of white matter fibre tracts causes the diffusion to be anisotropic. From the DTI data, one can calculate a vector field representing the preferred direction of diffusion at each imaging voxel, which corresponds to the orientation of white matter fibres. However, the reconstruction of continuous fibre tracts from such data remains a challenge because the measurements are dense and typically quite noisy. In this paper we introduce a geometric flow to address this problem. The key ideas are: 1) to locally extend the vector field in its orthogonal plane and 2) to model the fibres as very thin tubes, by introducing a constraint on the minimum cross-sectional curvature. We illustrate the approach with reconstructions of both simulated and real diffusion tensor images.

Validation and regularization in diffusion MRI tractography

We present a physical phantom designed for fibre tractography validation and use it to evaluate tracking algorithms that employ (a) the classic diffusion tensor model of diffusion, (b) high angular resolution reconstruction of the diffusion orientation distribution function (ODF), and (c) a regularization algorithm capable of inferring complex subvoxel fibre configurations. This work addresses four issues in diffusion MRI tractography: validation of the tracking process using ground truth, evaluation of different approaches for diffusion ODF reconstruction, coping with imaging noise, and coping with confounding subvoxel fibre configurations