Ben Jeurissen

Investigating the Prevalence of Complex Fiber Configurations in White Matter Tissue with Diffusion Magnetic Resonance Imaging

It has long been recognized that the diffusion tensor model is inappropriate to characterize complex fiber architecture, causing tensor‐derived measures such as the primary eigenvector and fractional anisotropy to be unreliable or misleading in these regions. There is however still debate about the impact of this problem in practice. A recent study using a Bayesian automatic relevance detection (ARD) multicompartment model suggested that a third of white matter (WM) voxels contain crossing fibers, a value that, whilst already significant, is likely to be an underestimate. The aim of this study is to provide more robust estimates of the proportion of affected voxels, the number of fiber orientations within each WM voxel, and the impact on tensor‐derived analyses, using large, high‐quality diffusion‐weighted data sets, with reconstruction parameters optimized specifically for this task. Two reconstruction algorithms were used: constrained spherical deconvolution (CSD), and the ARD method used in the previous study. We estimate the proportion of WM voxels containing crossing fibers to be ∼90% (using CSD) and 63% (using ARD). Both these values are much higher than previously reported, strongly suggesting that the diffusion tensor model is inadequate in the vast majority of WM regions. This has serious implications for downstream processing applications that depend on this model, particularly tractography, and the interpretation of anisotropy and radial/axial diffusivity measures. Hum Brain Mapp 34:2747–2766, 2013.

Probabilistic fiber tracking using the residual bootstrap with constrained spherical deconvolution.

Constrained spherical deconvolution (CSD) is a new technique that, based on high‐angular resolution diffusion imaging (HARDI) MR data, estimates the orientation of multiple intravoxel fiber populations within regions of complex white matter architecture, thereby overcoming the limitations of the widely used diffusion tensor imaging (DTI) technique. One of its main applications is fiber tractography. The noisy nature of diffusion‐weighted (DW) images, however, affects the estimated orientations and the resulting fiber trajectories will be subject to uncertainty. The impact of noise can be large, especially for HARDI measurements, which employ relatively high b‐values. To quantify the effects of noise on fiber trajectories, probabilistic tractography was introduced, which considers multiple possible pathways emanating from one seed point, taking into account the uncertainty of local fiber orientations. In this work, a probabilistic tractography algorithm is presented based on CSD and the residual bootstrap. CSD, which provides accurate and precise estimates of multiple fiber orientations, is used to extract the local fiber orientations. The residual bootstrap is used to estimate fiber tract probability within a clinical time frame, without prior assumptions about the form of uncertainty in the data. By means of Monte Carlo simulations, the performance of the CSD fiber pathway uncertainty estimator is measured in terms of accuracy and precision. In addition, the performance of the proposed method is compared to state‐of‐the‐art DTI residual bootstrap tractography and to an existing probabilistic CSD tractography algorithm using clinical DW data. Hum Brain Mapp, 2011.

Multi-tissue constrained spherical deconvolution for improved analysis of multi-shell diffusion MRI data

Constrained spherical deconvolution (CSD) has become one of the most widely used methods to extract white matter (WM) fibre orientation information from diffusion-weighted MRI (DW-MRI) data, overcoming the crossing fibre limitations inherent in the diffusion tensor model. It is routinely used to obtain high quality fibre orientation distribution function (fODF) estimates and fibre tractograms and is increasingly used to obtain apparent fibre density (AFD) measures. Unfortunately, CSD typically only supports data acquired on a single shell in q-space. With multi-shell data becoming more and more prevalent, there is a growing need for CSD to fully support such data. Furthermore, CSD can only provide high quality fODF estimates in voxels containing WM only. In voxels containing other tissue types such as grey matter (GM) and cerebrospinal fluid (CSF), the WM response function may no longer be appropriate and spherical deconvolution produces unreliable, noisy fODF estimates. The aim of this study is to incorporate support for multi-shell data into the CSD approach as well as to exploit the unique b-value dependencies of the different tissue types to estimate a multi-tissue ODF. The resulting approach is dubbed multi-shell, multi-tissue CSD (MSMT-CSD) and is compared to the state-of-the-art single-shell, single-tissue CSD (SSST-CSD) approach. Using both simulations and real data, we show that MSMT-CSD can produce reliable WM/GM/CSF volume fraction maps, directly from the DW data, whereas SSST-CSD has a tendency to overestimate the WM volume in voxels containing GM and/or CSF. In addition, compared to SSST-CSD, MSMT-CSD can substantially increase the precision of the fODF fibre orientations and reduce the presence of spurious fODF peaks in voxels containing GM and/or CSF. Both effects translate into more reliable AFD measures and tractography results with MSMT-CSD compared to SSST-CSD.

Weighted linear least squares estimation of diffusion MRI parameters: Strengths, limitations, and pitfalls

PURPOSE Linear least squares estimators are widely used in diffusion MRI for the estimation of diffusion parameters. Although adding proper weights is necessary to increase the precision of these linear estimators, there is no consensus on how to practically define them. In this study, the impact of the commonly used weighting strategies on the accuracy and precision of linear diffusion parameter estimators is evaluated and compared with the nonlinear least squares estimation approach. METHODS Simulation and real data experiments were done to study the performance of the weighted linear least squares estimators with weights defined by (a) the squares of the respective noisy diffusion-weighted signals; and (b) the squares of the predicted signals, which are reconstructed from a previous estimate of the diffusion model parameters. RESULTS The negative effect of weighting strategy (a) on the accuracy of the estimator was surprisingly high. Multi-step weighting strategies yield better performance and, in some cases, even outperformed the nonlinear least squares estimator. CONCLUSION If proper weighting strategies are applied, the weighted linear least squares approach shows high performance characteristics in terms of accuracy/precision and may even be preferred over nonlinear estimation methods.

The influence of complex white matter architecture on the mean diffusivity in diffusion tensor MRI of the human brain

In diffusion tensor magnetic resonance imaging (DT-MRI), limitations concerning complex fiber architecture (when an image voxel contains fiber populations with more than one dominant orientation) are well-known. Fractional anisotropy (FA) values are lower in such areas because of a lower directionality of diffusion on the voxel-scale, which makes the interpretation of FA less straightforward. Moreover, the interpretation of the axial and radial diffusivities is far from trivial when there is more than one dominant fiber orientation within a voxel. In this work, using (i) theoretical considerations, (ii) simulations, and (iii) experimental data, it is demonstrated that the mean diffusivity (or the trace of the diffusion tensor) is lower in complex white matter configurations, compared with tissue where there is a single dominant fiber orientation within the voxel. We show that the magnitude of this reduction depends on various factors, including configurational and microstructural properties (e.g., the relative contributions of different fiber populations) and acquisition settings (e.g., the b-value). These results increase our understanding of the quantitative metrics obtained from DT-MRI and, in particular, the effect of the microstructural architecture on the mean diffusivity. More importantly, they reinforce the growing awareness that differences in DT-MRI metrics need to be interpreted cautiously.

Limbic and callosal white matter changes in euthymic bipolar I disorder: an advanced diffusion magnetic resonance imaging tractography study.

BACKGROUND White matter microstructural changes detected using diffusion tensor imaging have been reported in bipolar disorder. However, findings are heterogeneous, which may be related to the use of analysis techniques that cannot adequately model crossing fibers in the brain. We therefore sought to identify altered diffusion anisotropy and diffusivity changes using an improved high angular resolution fiber-tracking technique. METHODS Diffusion magnetic resonance imaging data was obtained from 35 prospectively confirmed euthymic bipolar disorder type 1 patients (age 22-59) and 43 control subjects (age 22-59) drawn from a sample of 120 age- and gender-matched demographically similar case-control pairs. Tractography using a constrained spherical deconvolution approach to account for crossing fibers was implemented. Changes in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity between patient and control groups in subdivisions of the corpus callosum, cingulum, and fornix were measured as indicators of trait differences in white matter microstructural organization in bipolar disorder. RESULTS Patients had significantly reduced fractional anisotropy and increased mean diffusivity and radial diffusivity in all divisions of the corpus callosum, left fornix, and subgenual cingulum compared with control subjects. Axial diffusivity was increased in the fornix bilaterally and right dorsal-anterior cingulum. CONCLUSIONS By using an improved fiber-tracking method in a clinically homogeneous population, we were able to localize trait diffusivity changes to specific subdivisions of limbic fiber pathways, including the fornix. Our findings extend previous reports of altered limbic system microstructural disorganization as a trait feature of bipolar disorder.

Comparing isotropic and anisotropic smoothing for voxel‐based DTI analyses: A simulation study

Voxel‐based analysis (VBA) methods are increasingly being used to compare diffusion tensor image (DTI) properties across different populations of subjects. Although VBA has many advantages, its results are highly dependent on several parameter settings, such as those from the coregistration technique applied to align the data, the smoothing kernel, the statistics, and the post‐hoc analyses. In particular, to increase the signal‐to‐noise ratio and to mitigate the adverse effect of residual image misalignments, DTI data are often smoothed before VBA with an isotropic Gaussian kernel with a full width half maximum up to 16 × 16 × 16 mm3. However, using isotropic smoothing kernels can significantly partial volume or voxel averaging artifacts, adversely affecting the true diffusion properties of the underlying fiber tissue. In this work, we compared VBA results between the isotropic and an anisotropic Gaussian filtering method using a simulated framework. Our results clearly demonstrate an increased sensitivity and specificity of detecting a predefined simulated pathology when the anisotropic smoothing kernel was used. Hum Brain Mapp, 2010.

Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography.

Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with “crossing fibers.” Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of “crossing fibers” on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer’s disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of “crossing fibers,” i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with “crossing fibers” the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture.

Maximum likelihood estimation-based denoising of magnetic resonance images using restricted local neighborhoods

In this paper, we propose a method to denoise magnitude magnetic resonance (MR) images, which are Rician distributed. Conventionally, maximum likelihood methods incorporate the Rice distribution to estimate the true, underlying signal from a local neighborhood within which the signal is assumed to be constant. However, if this assumption is not met, such filtering will lead to blurred edges and loss of fine structures. As a solution to this problem, we put forward the concept of restricted local neighborhoods where the true intensity for each noisy pixel is estimated from a set of preselected neighboring pixels. To this end, a reference image is created from the noisy image using a recently proposed nonlocal means algorithm. This reference image is used as a prior for further noise reduction. A scheme is developed to locally select an appropriate subset of pixels from which the underlying signal is estimated. Experimental results based on the peak signal to noise ratio, structural similarity index matrix, Bhattacharyya coefficient and mean absolute difference from synthetic and real MR images demonstrate the superior performance of the proposed method over other state-of-the-art methods.

Isotropic non-white matter partial volume effects in constrained spherical deconvolution.

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive imaging method, which can be used to investigate neural tracts in the white matter (WM) of the brain. Significant partial volume effects (PVEs) are present in the DW signal due to relatively large voxel sizes. These PVEs can be caused by both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and by multiple non-parallel WM fiber populations. High angular resolution diffusion imaging (HARDI) methods have been developed to correctly characterize complex WM fiber configurations, but to date, many of the HARDI methods do not account for non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM tissue in WM voxels on fiber orientations extracted with constrained spherical deconvolution (CSD). Experiments were performed on simulated and real DW-MRI data. In particular, simulations were performed to demonstrate the effects of varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber configurations, and tissue fractions. Our results show that the presence of non-WM tissue signal causes a decrease in the precision of the detected fiber orientations and an increase in the detection of false peaks in CSD. We estimated 35–50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which typically have a relatively high degree of diffusion weighting, these adverse effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe with 50% GM volume for maximum spherical harmonics orders of 8 and below, and already with 25% GM volume for higher orders. In addition, a low diffusion weighting or SNR increases the effects. The non-WM PVEs may cause problems in connectomics, where reliable fiber tracking at the WM–GM interface is especially important. We suggest acquiring data with high diffusion-weighting 2500–3000 s/mm2, reasonable SNR (~30) and using lower SH orders in GM contaminated regions to minimize the non-WM PVEs in CSD.