Consensus-based guidance for conducting and reporting multi-analyst studies.

Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.

Harmonization of diffusion MRI data sets with adaptive dictionary learning.

Diffusion magnetic resonance imaging can indirectly infer the microstructure of tissues and provide metrics subject to normal variability in a population. Potentially abnormal values may yield essential information to support analysis of controls and patients cohorts, but subtle confounds could be mistaken for purely biologically driven variations amongst subjects. In this work, we propose a new harmonization algorithm based on adaptive dictionary learning to mitigate the unwanted variability caused by different scanner hardware while preserving the natural biological variability of the data. Our harmonization algorithm does not require paired training data sets, nor spatial registration or matching spatial resolution. Overcomplete dictionaries are learned iteratively from all data sets at the same time with an adaptive regularization criterion, removing variability attributable to the scanners in the process. The obtained mapping is applied directly in the native space of each subject toward a scanner-space. The method is evaluated with a public database which consists of two different protocols acquired on three different scanners. Results show that the effect size of the four studied diffusion metrics is preserved while removing variability attributable to the scanner. Experiments with alterations using a free water compartment, which is not simulated in the training data, shows that the modifications applied to the diffusion weighted images are preserved in the diffusion metrics after harmonization, while still reducing global variability at the same time. The algorithm could help multicenter studies pooling their data by removing scanner specific confounds, and increase statistical power in the process.

Automated characterization of noise distributions in diffusion MRI data.

Knowledge of the noise distribution in magnitude diffusion MRI images is the centerpiece to quantify uncertainties arising from the acquisition process. The use of parallel imaging methods, the number of receiver coils and imaging filters applied by the scanner, amongst other factors, dictate the resulting signal distribution. Accurate estimation beyond textbook Rician or noncentral chi distributions often requires information about the acquisition process (e.g., coils sensitivity maps or reconstruction coefficients), which is usually not available. We introduce two new automated methods using the moments and maximum likelihood equations of the Gamma distribution to estimate noise distributions as they explicitly depend on the number of coils, making it possible to estimate all unknown parameters using only the magnitude data. A rejection step is used to make the framework automatic and robust to artifacts. Simulations using stationary and spatially varying noncentral chi noise distributions were created for two diffusion weightings with SENSE or GRAPPA reconstruction and 8, 12 or 32 receiver coils. Furthermore, MRI data of a water phantom with different combinations of parallel imaging were acquired on a 3T Philips scanner along with noise-only measurements. Finally, experiments on freely available datasets from a single subject acquired on a 3T GE scanner are used to assess reproducibility when limited information about the acquisition protocol is available. Additionally, we demonstrated the applicability of the proposed methods for a bias correction and denoising task on an in vivo dataset acquired on a 3T Siemens scanner. A generalized version of the bias correction framework for non integer degrees of freedom is also introduced. The proposed framework is compared with three other algorithms with datasets from three vendors, employing different reconstruction methods. Simulations showed that assuming a Rician distribution can lead to misestimation of the noise distribution in parallel imaging. Results on the acquired datasets showed that signal leakage in multiband can also lead to a misestimation of the noise distribution. Repeated acquisitions of in vivo datasets show that the estimated parameters are stable and have lower variability than compared methods. Results for the bias correction and denoising task show that the proposed methods reduce the appearance of noise at high b-value. The proposed algorithms herein can estimate both parameters of the noise distribution automatically, are robust to signal leakage artifacts and perform best when used on acquired noise maps.

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.

Reducing variability in along-tract analysis with diffusion profile realignment.

Diffusion weighted magnetic resonance imaging (dMRI) provides a non invasive virtual reconstruction of the brain's white matter structures through tractography. Analyzing dMRI measures along the trajectory of white matter bundles can provide a more specific investigation than considering a region of interest or tract-averaged measurements. However, performing group analyses with this along-tract strategy requires correspondence between points of tract pathways across subjects. This is usually achieved by creating a new common space where the representative streamlines from every subject are resampled to the same number of points. If the underlying anatomy of some subjects was altered due to, e.g., disease or developmental changes, such information might be lost by resampling to a fixed number of points. In this work, we propose to address the issue of possible misalignment, which might be present even after resampling, by realigning the representative streamline of each subject in this 1D space with a new method, coined diffusion profile realignment (DPR). Experiments on synthetic datasets show that DPR reduces the coefficient of variation for the mean diffusivity, fractional anisotropy and apparent fiber density when compared to the unaligned case. Using 100 in vivo datasets from the human connectome project, we simulated changes in mean diffusivity, fractional anisotropy and apparent fiber density. Independent Student's t-tests between these altered subjects and the original subjects indicate that regional changes are identified after realignment with the DPR algorithm, while preserving differences previously detected in the unaligned case. This new correction strategy contributes to revealing effects of interest which might be hidden by misalignment and has the potential to improve the specificity in longitudinal population studies beyond the traditional region of interest based analysis and along-tract analysis workflows.

Cross-scanner and cross-protocol diffusion MRI data harmonisation: A benchmark database and evaluation of algorithms.

Diffusion MRI is being used increasingly in studies of the brain and other parts of the body for its ability to provide quantitative measures that are sensitive to changes in tissue microstructure. However, inter-scanner and inter-protocol differences are known to induce significant measurement variability, which in turn jeopardises the ability to obtain 'truly quantitative measures' and challenges the reliable combination of different datasets. Combining datasets from different scanners and/or acquired at different time points could dramatically increase the statistical power of clinical studies, and facilitate multi-centre research. Even though careful harmonisation of acquisition parameters can reduce variability, inter-protocol differences become almost inevitable with improvements in hardware and sequence design over time, even within a site. In this work, we present a benchmark diffusion MRI database of the same subjects acquired on three distinct scanners with different maximum gradient strength (40, 80, and 300 mT/m), and with 'standard' and 'state-of-the-art' protocols, where the latter have higher spatial and angular resolution. The dataset serves as a useful testbed for method development in cross-scanner/cross-protocol diffusion MRI harmonisation and quality enhancement. Using the database, we compare the performance of five different methods for estimating mappings between the scanners and protocols. The results show that cross-scanner harmonisation of single-shell diffusion data sets can reduce the variability between scanners, and highlight the promises and shortcomings of today's data harmonisation techniques.

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.

Non Local Spatial and Angular Matching: Enabling higher spatial resolution diffusion MRI datasets through adaptive denoising.

Diffusion magnetic resonance imaging (MRI) datasets suffer from low Signal-to-Noise Ratio (SNR), especially at high b-values. Acquiring data at high b-values contains relevant information and is now of great interest for microstructural and connectomics studies. High noise levels bias the measurements due to the non-Gaussian nature of the noise, which in turn can lead to a false and biased estimation of the diffusion parameters. Additionally, the usage of in-plane acceleration techniques during the acquisition leads to a spatially varying noise distribution, which depends on the parallel acceleration method implemented on the scanner. This paper proposes a novel diffusion MRI denoising technique that can be used on all existing data, without adding to the scanning time. We first apply a statistical framework to convert both stationary and non stationary Rician and non central Chi distributed noise to Gaussian distributed noise, effectively removing the bias. We then introduce a spatially and angular adaptive denoising technique, the Non Local Spatial and Angular Matching (NLSAM) algorithm. Each volume is first decomposed in small 4D overlapping patches, thus capturing the spatial and angular structure of the diffusion data, and a dictionary of atoms is learned on those patches. A local sparse decomposition is then found by bounding the reconstruction error with the local noise variance. We compare against three other state-of-the-art denoising methods and show quantitative local and connectivity results on a synthetic phantom and on an in-vivo high resolution dataset. Overall, our method restores perceptual information, removes the noise bias in common diffusion metrics, restores the extracted peaks coherence and improves reproducibility of tractography on the synthetic dataset. On the 1.2 mm high resolution in-vivo dataset, our denoising improves the visual quality of the data and reduces the number of spurious tracts when compared to the noisy acquisition. Our work paves the way for higher spatial resolution acquisition of diffusion MRI datasets, which could in turn reveal new anatomical details that are not discernible at the spatial resolution currently used by the diffusion MRI community.

Sparse Reconstruction Challenge for diffusion MRI: Validation on a physical phantom to determine which acquisition scheme and analysis method to use?

Diffusion magnetic resonance imaging (dMRI) is the modality of choice for investigating in-vivo white matter connectivity and neural tissue architecture of the brain. The diffusion-weighted signal in dMRI reflects the diffusivity of water molecules in brain tissue and can be utilized to produce image-based biomarkers for clinical research. Due to the constraints on scanning time, a limited number of measurements can be acquired within a clinically feasible scan time. In order to reconstruct the dMRI signal from a discrete set of measurements, a large number of algorithms have been proposed in recent years in conjunction with varying sampling schemes, i.e., with varying b-values and gradient directions. Thus, it is imperative to compare the performance of these reconstruction methods on a single data set to provide appropriate guidelines to neuroscientists on making an informed decision while designing their acquisition protocols. For this purpose, the SPArse Reconstruction Challenge (SPARC) was held along with the workshop on Computational Diffusion MRI (at MICCAI 2014) to validate the performance of multiple reconstruction methods using data acquired from a physical phantom. A total of 16 reconstruction algorithms (9 teams) participated in this community challenge. The goal was to reconstruct single b-value and/or multiple b-value data from a sparse set of measurements. In particular, the aim was to determine an appropriate acquisition protocol (in terms of the number of measurements, b-values) and the analysis method to use for a neuroimaging study. The challenge did not delve on the accuracy of these methods in estimating model specific measures such as fractional anisotropy (FA) or mean diffusivity, but on the accuracy of these methods to fit the data. This paper presents several quantitative results pertaining to each reconstruction algorithm. The conclusions in this paper provide a valuable guideline for choosing a suitable algorithm and the corresponding data-sampling scheme for clinical neuroscience applications.