Double Diffusion Encoding Prevents Degeneracy in Parameter Estimation of Biophysical Models in Diffusion MRI

Purpose: Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, the general Standard Model has recently shown that model parameter estimation from dMRI data is ill-posed unless very strong magnetic gradients are used. We analyse this issue for the Neurite Orientation Dispersion and Density Imaging with Diffusivity Assessment (NODDIDA) model and demonstrate that its extension from Single Diffusion Encoding (SDE) to Double Diffusion Encoding (DDE) solves the ill-posedness and increases the accuracy of the parameter estimation. Methods: We analyse theoretically the cumulant expansion up to fourth order in b of SDE and DDE signals. Additionally, we perform in silico experiments to compare SDE and DDE capabilities under similar noise conditions. Results: We prove analytically that DDE provides invariant information non-accessible from SDE, which makes the NODDIDA parameter estimation injective. The in silico experiments show that DDE reduces the bias and mean square error of the estimation along the whole feasible region of 5D model parameter space. Conclusions: DDE adds additional information for estimating the model parameters, unexplored by SDE, which is enough to solve the degeneracy in the NODDIDA model parameter estimation.Comment: 22 pages, 7 figure

Lossy compression of multidimensional medical images using sinusoidal activation networks: an evaluation study

In this work, we evaluate how neural networks with periodic activation functions can be leveraged to reliably compress large multidimensional medical image datasets, with proof-of-concept application to 4D diffusion-weighted MRI (dMRI). In the medical imaging landscape, multidimensional MRI is a key area of research for developing biomarkers that are both sensitive and specific to the underlying tissue microstructure. However, the high-dimensional nature of these data poses a challenge in terms of both storage and sharing capabilities and associated costs, requiring appropriate algorithms able to represent the information in a low-dimensional space. Recent theoretical developments in deep learning have shown how periodic activation functions are a powerful tool for implicit neural representation of images and can be used for compression of 2D images. Here we extend this approach to 4D images and show how any given 4D dMRI dataset can be accurately represented through the parameters of a sinusoidal activation network, achieving a data compression rate about 10 times higher than the standard DEFLATE algorithm. Our results show that the proposed approach outperforms benchmark ReLU and Tanh activation perceptron architectures in terms of mean squared error, peak signal-to-noise ratio and structural similarity index. Subsequent analyses using the tensor and spherical harmonics representations demonstrate that the proposed lossy compression reproduces accurately the characteristics of the original data, leading to relative errors about 5 to 10 times lower than the benchmark JPEG2000 lossy compression and similar to standard pre-processing steps such as MP-PCA denosing, suggesting a loss of information within the currently accepted levels for clinical application

Direction-averaged diffusion-weighted MRI signal using different axisymmetric B-tensor encoding schemes

Purpose: It has been shown, theoretically and in vivo, that using the Stejskal-Tannerpulsed-gradient, or linear tensor encoding (LTE), and in exhibiting a ’stick-like’ diffusion geometry,the direction-averaged diffusion-weighted MRI signal at high b-values (7000 < b <10000 s=mm2) follows a power-law, decaying as 1=pb. It has also been shown, theoretically,that for planar tensor encoding (PTE), the direction-averaged signal decays as 1=b. We aimedto confirm this theoretical prediction in vivo. We then considered the direction-averaged signalfor arbitrary b-tensor shapes and different tissue substrates to look for other conditions underwhich a power-law exists.Methods: We considered the signal decay for high b-values for encoding geometries rangingfrom 2-dimensional PTE, through isotropic or spherical tensor encoding (STE) to LTE. Whena power-law behaviour was suggested, this was tested using in silico simulations and in vivousing ultra-strong gradients (300 mT/m).Results: Our in vivo results confirmed the predicted 1/b power law for PTE. Moreover, ouranalysis showed that using an axisymmetric b-tensor a power-law only exists under very specificconditions: (a) the tissue must have ’stick-like’ geometry; and (b) the waveform must bepurely LTE or purely PTE.Conclusion: A complete analysis of the power-law dependencies of the diffusion-weightedsignal at high b-values has been performed. Only two specific forms of encoding result in apower-law dependency, pure linear and pure planar tensor encoding and when the microstructuralgeometry is ’stick-like’. The different exponents of these encodings could be used toprovide independent validation of the presence of stick-like geometries in vivo

Including diffusion time dependence in the extra-axonal space improves in vivo estimates of axonal diameter and density in human white matter

Axonal density and diameter are two fundamental properties of brain white matter. Recently, advanced diffusion MRI techniques have made these two parameters accessible in vivo. However, the techniques available to estimate such parameters are still under development. For example, current methods to map axonal diameters capture relative trends over different structures, but consistently over-estimate absolute diameters. Axonal density estimates are more accessible experimentally, but different modeling approaches exist and the impact of the experimental parameters has not been thoroughly quantified, potentially leading to incompatibility of results obtained in different studies using different techniques. Here, we characterise the impact of diffusion time on axonal density and diameter estimates using Monte Carlo simulations and STEAM diffusion MRI at 7 T on 9 healthy volunteers. We show that axonal density and diameter estimates strongly depend on diffusion time, with diameters almost invariably overestimated and density both over and underestimated for some commonly used models. Crucially, we also demonstrate that these biases are reduced when the model accounts for diffusion time dependency in the extra-axonal space. For axonal density estimates, both upward and downward bias in different situations are removed by modeling extra-axonal time-dependence, showing increased accuracy in these estimates. For axonal diameter estimates, we report increased accuracy in ground truth simulations and axonal diameter estimates decreased away from high values given by earlier models and towards known values in the human corpus callosum when modeling extra-axonal time-dependence. Axonal diameter feasibility under both advanced and clinical settings is discussed in the light of the proposed advances

Meyer's loop tractography for image-guided surgery depends on imaging protocol and hardware

Introduction Surgical resection is an effective treatment for temporal lobe epilepsy but can result in visual field defects. This could be minimized if surgeons knew the exact location of the anterior part of the optic radiation (OR), the Meyer's loop. To this end, there is increasing prevalence of image-guided surgery using diffusion MRI tractography. Despite considerable effort in developing analysis methods, a wide discrepancy in Meyer's loop reconstructions is observed in the literature. Moreover, the impact of differences in image acquisition on Meyer's loop tractography remains unclear. Here, while employing the same state-of-the-art analysis protocol, we explored the extent to which variance in data acquisition leads to variance in OR reconstruction. Methods Diffusion MRI data were acquired for the same thirteen healthy subjects using standard and state-of-the-art protocols on three scanners with different maximum gradient amplitudes (MGA): Siemens Connectom (MGA = 300 mT/m); Siemens Prisma (MGA = 80 mT/m) and GE Excite-HD (MGA = 40 mT/m). Meyer's loop was reconstructed on all subjects and its distance to the temporal pole (ML-TP) was compared across protocols. Results A significant effect of data acquisition on the ML-TP distance was observed between protocols (p < .01 to 0.0001). The biggest inter-acquisition discrepancy for the same subject across different protocols was 16.5 mm (mean: 9.4 mm, range: 3.7–16.5 mm). Conclusion We showed that variance in data acquisition leads to substantive variance in OR tractography. This has direct implications for neurosurgical planning, where part of the OR is at risk due to an under-estimation of its location using conventional acquisition protocols

The dot-compartment revealed? Diffusion MRI with ultra-strong gradients and spherical tensor encoding in the living human brain

The so-called “dot-compartment” is conjectured in diffusion MRI to represent small spherical spaces, such as cell bodies, in which the diffusion is restricted in all directions. Previous investigations inferred its existence from data acquired with directional diffusion encoding which does not permit a straightforward separation of signals from ‘sticks’ (axons) and signals from ‘dots’. Here we combine isotropic diffusion encoding with ultra-strong diffusion gradients (240 mT/m) to achieve high diffusion-weightings with high signal to noise ratio, while suppressing signal arising from anisotropic water compartments with significant mobility along at least one axis (e.g., axons). A dot-compartment, defined to have apparent diffusion coefficient equal to zero and no exchange, would result in a non-decaying signal at very high b-values (b 7000 s/mm2). With this unique experimental setup, a residual yet slowly decaying, signal above the noise floor for b-values as high as 15 000 s/mm2 was seen clearly in the cerebellar grey matter (GM), and in several white matter (WM) regions to some extent. Upper limits of the dot-signal-fraction were estimated to be 1.8% in cerebellar GM and 0.2% in WM. By relaxing the assumption of zero diffusivity, the signal at high b-values in cerebellar GM could be represented more accurately by an isotropic water pool with a low apparent diffusivity of 0.12 and a substantial signal fraction of 9.7%. The T2 of this component was estimated to be around 61 m s. This remaining signal at high b-values has potential to serve as a novel and simple marker for isotropically-restricted water compartments in cerebellar GM

Dynamics of the human structural connectome underlying working memory training

Brain region-specific changes have been demonstrated with a variety of cognitive training interventions. The effect of cognitive training on brain subnetworks in humans, however, remains largely unknown, with studies limited to functional networks. Here, we used a well-established working memory training program and state-of-the art neuroimaging methods in 40 healthy adults (21 females, mean age 26.5 years). Near and far-transfer training effects were assessed using computerized working memory and executive function tasks. Adaptive working memory training led to improvement on (non)trained working memory tasks and generalization to tasks of reasoning and inhibition. Graph theoretical analysis of the structural (white matter) network connectivity (“connectome”) revealed increased global integration within a frontoparietal attention network following adaptive working memory training compared with the nonadaptive group. Furthermore, the impact on the outcome of graph theoretical analyses of different white matter metrics to infer “connection strength” was evaluated. Increased efficiency of the frontoparietal network was best captured when using connection strengths derived from MR metrics that are thought to be more sensitive to differences in myelination (putatively indexed by the [quantitative] longitudinal relaxation rate, R1) than previously used diffusion MRI metrics (fractional anisotropy or fiber-tracking recovered streamlines). Our findings emphasize the critical role of specific microstructural markers in providing important hints toward the mechanisms underpinning training-induced plasticity that may drive working memory improvement in clinical populations

Longitudinal data on cortical thickness before and after working memory training

The data and supplementary information provided in this article relate to our research article “Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training.” [1]. We provide cortical thickness and subcortical volume data derived from parieto-frontal cortical regions and the basal ganglia with the FreeSurfer longitudinal analyses stream (http://surfer.nmr.mgh.harvard.edu [2]) before and after working memory training, “Cogmed and Cogmed Working Memory Training” [3]. This article also provides supplementary information to the research article, i.e., within-group comparisons between baseline and outcome cortical thickness and subcortical volume measures, between-group tests of performance changes in cognitive benchmark tests (www.cambridgebrainsciences.com[4]), correlation analyses between performance changes in benchmark tests and training-related structural changes, correlation analyses between the time spent training and structural changes, a scatterplot of the relationship between cortical thickness measures derived from the occipital lobe as control region and the chronological order of the MRI sessions to assess potential scanner drift effects and a post-hoc vertex-wise whole brain analysis with FreeSurfer Qdec (https://surfer.nmr.mgh.harvard.edu/fswiki/Qdec [5])