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.

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.

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

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.

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.