Edge illumination x-ray phase contrast simulations using the CAD-ASTRA toolbox.

Edge illumination x-ray phase contrast imaging (XPCI) provides increased contrast for low absorbing materials compared to attenuation images and sheds light on the material microstructure through dark field contrast. To apply XPCI in areas such as non-destructive testing and inline inspection, where scanned samples are increasingly compared to simulated reference images, accurate and efficient simulation software is required. However, currently available simulators rely on expensive Monte Carlo techniques or wave-optics frameworks, resulting in long simulation times. Furthermore, these simulators are often not optimized to work with computer-aided design (CAD) models, a common and memory-efficient method to represent manufactured objects, hindering their integration in an inspection pipeline. In this work, we address these shortcomings by introducing an edge illumination XPCI simulation framework built upon the recently developed CAD-ASTRA toolbox. CAD-ASTRA allows for the efficient simulation of x-ray projections from CAD models through GPU-accelerated ray tracing and supports ray refraction in a geometric optics framework. The edge illumination implementation is validated and its performance is benchmarked against GATE, a state-of-the-art Monte Carlo simulator, revealing a simulation speed increase of up to three orders of magnitude, while maintaining high accuracy in the resulting images.

Automated Landmark Annotation for Morphometric Analysis of Distal Femur and Proximal Tibia.

Manual anatomical landmarking for morphometric knee bone characterization in orthopedics is highly time-consuming and shows high operator variability. Therefore, automation could be a substantial improvement for diagnostics and personalized treatments relying on landmark-based methods. Applications include implant sizing and planning, meniscal allograft sizing, and morphological risk factor assessment. For twenty MRI-based 3D bone and cartilage models, anatomical landmarks were manually applied by three experts, and morphometric measurements for 3D characterization of the distal femur and proximal tibia were calculated from all observations. One expert performed the landmark annotations three times. Intra- and inter-observer variations were assessed for landmark position and measurements. The mean of the three expert annotations served as the ground truth. Next, automated landmark annotation was performed by elastic deformation of a template shape, followed by landmark optimization at extreme positions (highest/lowest/most medial/lateral point). The results of our automated annotation method were compared with ground truth, and percentages of landmarks and measurements adhering to different tolerances were calculated. Reliability was evaluated by the intraclass correlation coefficient (ICC). For the manual annotations, the inter-observer absolute difference was 1.53 ± 1.22 mm (mean ± SD) for the landmark positions and 0.56 ± 0.55 mm (mean ± SD) for the morphometric measurements. Automated versus manual landmark extraction differed by an average of 2.05 mm. The automated measurements demonstrated an absolute difference of 0.78 ± 0.60 mm (mean ± SD) from their manual counterparts. Overall, 92% of the automated landmarks were within 4 mm of the expert mean position, and 95% of all morphometric measurements were within 2 mm of the expert mean measurements. The ICC (manual versus automated) for automated morphometric measurements was between 0.926 and 1. Manual annotations required on average 18 min of operator interaction time, while automated annotations only needed 7 min of operator-independent computing time. Considering the time consumption and variability among observers, there is a clear need for a more efficient, standardized, and operator-independent algorithm. Our automated method demonstrated excellent accuracy and reliability for landmark positioning and morphometric measurements. Above all, this automated method will lead to a faster, scalable, and operator-independent morphometric analysis of the knee.

Model-based super-resolution reconstruction for pseudo-continuous Arterial Spin Labeling.

Arterial spin labeling (ASL) is a promising, non-invasive perfusion magnetic resonance imaging technique for quantifying cerebral blood flow (CBF). Unfortunately, ASL suffers from an inherently low signal-to-noise ratio (SNR) and spatial resolution, undermining its potential. Increasing spatial resolution without significantly sacrificing SNR or scan time represents a critical challenge towards routine clinical use. In this work, we propose a model-based super-resolution reconstruction (SRR) method with joint motion estimation that breaks the traditional SNR/resolution/scan-time trade-off. From a set of differently oriented 2D multi-slice pseudo-continuous ASL images with a low through-plane resolution, 3D-isotropic, high resolution, quantitative CBF maps are estimated using a Bayesian approach. Experiments on both synthetic whole brain phantom data, and on in vivo brain data, show that the proposed SRR Bayesian estimation framework outperforms state-of-the-art ASL quantification.

A preparation pulse for fast steady state approach in Actual Flip angle Imaging.

BACKGROUND: Actual Flip angle Imaging (AFI) is a sequence used for B1 mapping, also embedded in the Variable flip angle with AFI for simultaneous estimation of T1 , B1 and equilibrium magnetization. PURPOSE: To investigate the design of a preparation module for AFI to allow a fast approach to steady state (SS) without requiring the use of dummy acquisitions. METHODS: The features of a preparation module with a B1 insensitive adiabatic pulse, spoiler gradients, and a recovery time T r e c $T_{rec}$ were studied with simulations and validated via experiments and acquired with different k-space traveling strategies. The robustness of the flip angle of the preparation pulse on the acquired signal is studied. RESULTS: When a 90° adiabatic pulse is used, the forthcoming T r e c $T_{rec}$ can be expressed as a function of repetition times and AFI flip angle only as TR 1 ( n + cos α ) / ( 1 - cos 2 α ) $\mathrm{TR_1}(n+\cos \alpha )/(1-\cos ^2\alpha )$ , where n represents the ratio between the two repetition times of AFI. The robustness of the method is demonstrated by showing that using the values further away from 90° still allows for a faster approach to SS than the use of dummy pulses. CONCLUSIONS: The preparation module is particularly advantageous for low flip angles, as well as for AFI sequences that sample the center of the k-space early in the sequence, such as centric ordering acquisitions, and for ultrafast EPI-based AFI methods, thus allowing to reduce scanner overhead time.

Super-Resolution Reconstruction of Multi-Slice T2-W FLAIR MRI Improves Multiple Sclerosis Lesion Segmentation.

Due to acquisition time constraints, T2-w FLAIR MRI of Multiple Sclerosis (MS) patients is often acquired with multi-slice 2D protocols with a low through-plane resolution rather than with high-resolution 3D protocols. Automated lesion segmentation on such low-resolution (LR) images, however, performs poorly and leads to inaccurate lesion volume estimates. Super-resolution reconstruction (SRR) methods can then be used to obtain a high-resolution (HR) image from multiple LR images to serve as input for lesion segmentation. In this work, we evaluate the effect on MS lesion segmentation of three SRR approaches: one based on interpolation, a state-of-the-art self-supervised CNN-based strategy, and a recently proposed model-based SRR method. These SRR strategies were applied to LR acquisitions simulated from 3D T2-w FLAIR MRI of MS patients. Each SRR method was evaluated in terms of image reconstruction quality and subsequent lesion segmentation performance. When compared to segmentation on LR images, the three considered SRR strategies demonstrate improved lesion segmentation. Furthermore, in some scenarios, SRR achieves a similar segmentation performance compared to segmentation of HR images.Clinical relevance- This study demonstrates the positive impact of super-resolution reconstruction from T2-w FLAIR multi-slice MRI acquisitions on segmentation performance of MS lesions.

Grating designs for cone beam edge illumination X-ray phase contrast imaging: a simulation study.

Edge illumination is an emerging X-ray phase contrast imaging technique providing attenuation, phase and dark field contrast. Despite the successful transition from synchrotron to lab sources, the cone beam geometry of lab systems limits the effectiveness of using conventional planar gratings. The non-parallel incidence of X-rays introduces shadowing effects, worsening with increasing cone angle. To overcome this limitation, several alternative grating designs can be considered. In this paper, the effectiveness of three alternative designs is compared to conventional gratings using numerical simulations. Improvements in flux and contrast are discussed, taking into account practical considerations concerning the implementation of the designs.

Efficient iterative reconstruction with beam shape compensation for THz computed tomography.

Terahertz (THz) computed tomography is an emerging nondestructive and non-ionizing imaging method. Most THz reconstruction methods rely on the Radon transform, originating from x-ray imaging, in which x rays propagate in straight lines. However, a THz beam has a finite width, and ignoring its shape results in blurred reconstructed images. Moreover, accounting for the THz beam model in a straightforward way in an iterative reconstruction method results in extreme demands in memory and in slow convergence. In this paper, we propose an efficient iterative reconstruction that incorporates the THz beam shape, while avoiding the above disadvantages. Both simulation and real experiments show that our approach results in improved resolution recovery in the reconstructed image. Furthermore, we propose a suitable preconditioner to improve the convergence speed of our reconstruction.

Fiber Orientation Estimation from X-ray Dark Field Images of Fiber Reinforced Polymers Using Constrained Spherical Deconvolution.

The properties of fiber reinforced polymers are strongly related to the length and orientation of the fibers within the polymer matrix, the latter of which can be studied using X-ray computed tomography (XCT). Unfortunately, resolving individual fibers is challenging because they are small compared to the XCT voxel resolution and because of the low attenuation contrast between the fibers and the surrounding resin. To alleviate both problems, anisotropic dark field tomography via grating based interferometry (GBI) has been proposed. Here, the fiber orientations are extracted by applying a Funk-Radon transform (FRT) to the local scatter function. However, the FRT suffers from a low angular resolution, which complicates estimating fiber orientations for small fiber crossing angles. We propose constrained spherical deconvolution (CSD) as an alternative to the FRT to resolve fiber orientations. Instead of GBI, edge illumination phase contrast imaging is used because estimating fiber orientations with this technique has not yet been explored. Dark field images are generated by a Monte Carlo simulation framework. It is shown that the FRT cannot estimate the fiber orientation accurately for crossing angles smaller than 70∘, while CSD performs well down to a crossing angle of 50∘. In general, CSD outperforms the FRT in estimating fiber orientations.

Systematic review of reconstruction techniques for accelerated quantitative MRI.

PURPOSE: To systematically review the techniques that address undersampling artifacts in accelerated quantitative magnetic resonance imaging (qMRI). METHODS: A literature search was conducted using the Embase, Medline, Web of Science Core Collection, Coherence Central Register of Controlled Trials, and Google Scholar databases for studies, published before July 2022 proposing reconstruction techniques for accelerated qMRI. Studies are reviewed according to inclusion criteria, and included studies are categorized based on the methodology used. RESULTS: A total of 292 studies included in the review are categorized. A technical overview of each category is provided, and the categories are described in a unified mathematical framework. The distribution of the reviewed studies over time, application domain, and parameters of interest is illustrated. CONCLUSION: An increasing trend in the number of articles that propose new techniques for accelerated qMRI reconstruction indicates the importance of acceleration in qMRI. The techniques are mostly validated for relaxometry parameters and brain scans. The categories of techniques are compared based on theoretical grounds, highlighting existing trends and potential gaps in the field.

Use of Support Vector Machines Approach via ComBat Harmonized Diffusion Tensor Imaging for the Diagnosis and Prognosis of Mild Traumatic Brain Injury: A CENTER-TBI Study.

The prediction of functional outcome after mild traumatic brain injury (mTBI) is challenging. Conventional magnetic resonance imaging (MRI) does not do a good job of explaining the variance in outcome, as many patients with incomplete recovery will have normal-appearing clinical neuroimaging. More advanced quantitative techniques such as diffusion MRI (dMRI), can detect microstructural changes not otherwise visible, and so may offer a way to improve outcome prediction. In this study, we explore the potential of linear support vector classifiers (linearSVCs) to identify dMRI biomarkers that can predict recovery after mTBI. Simultaneously, the harmonization of fractional anisotropy (FA) and mean diffusivity (MD) via ComBat was evaluated and compared for the classification performances of the linearSVCs. We included dMRI scans of 179 mTBI patients and 85 controls from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a multi-center prospective cohort study, up to 21 days post-injury. Patients were dichotomized according to their Extended Glasgow Outcome Scale (GOSE) scores at 6 months into complete (n = 92; GOSE = 8) and incomplete (n = 87; GOSE <8) recovery. FA and MD maps were registered to a common space and harmonized via the ComBat algorithm. LinearSVCs were applied to distinguish: (1) mTBI patients from controls and (2) mTBI patients with complete from those with incomplete recovery. The linearSVCs were trained on (1) age and sex only, (2) non-harmonized, (3) two-category-harmonized ComBat, and (4) three-category-harmonized ComBat FA and MD images combined with age and sex. White matter FA and MD voxels and regions of interest (ROIs) within the John Hopkins University (JHU) atlas were examined. Recursive feature elimination was used to identify the 10% most discriminative voxels or the 10 most discriminative ROIs for each implementation. mTBI patients displayed significantly higher MD and lower FA values than controls for the discriminative voxels and ROIs. For the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD voxel-wise linearSVC provided significantly higher classification scores (81.4% accuracy, 93.3% sensitivity, 80.3% F1-score, and 0.88 area under the curve [AUC], p < 0.05) compared with the classification based on age and sex only and the ROI approaches (accuracies: 59.8% and 64.8%, respectively). Similar to the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD maps voxelwise approach yields statistically significant prediction scores between mTBI patients with complete and those with incomplete recovery (71.8% specificity, 66.2% F1-score and 0.71 AUC, p < 0.05), which provided a modest increase in the classification score (accuracy: 66.4%) compared with the classification based on age and sex only and ROI-wise approaches (accuracy: 61.4% and 64.7%, respectively). This study showed that ComBat harmonized FA and MD may provide additional information for diagnosis and prognosis of mTBI in a multi-modal machine learning approach. These findings demonstrate that dMRI may assist in the early detection of patients at risk of incomplete recovery from mTBI.

Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity.

The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.

Optimal experimental design and estimation for q-space trajectory imaging.

Tensor-valued diffusion encoding facilitates data analysis by q-space trajectory imaging. By modeling the diffusion signal of heterogeneous tissues with a diffusion tensor distribution (DTD) and modulating the encoding tensor shape, this novel approach allows disentangling variations in diffusivity from microscopic anisotropy, orientation dispersion, and mixtures of multiple isotropic diffusivities. To facilitate the estimation of the DTD parameters, a parsimonious acquisition scheme coupled with an accurate and precise estimation of the DTD is needed. In this work, we create two precision-optimized acquisition schemes: one that maximizes the precision of the raw DTD parameters, and another that maximizes the precision of the scalar measures derived from the DTD. The improved precision of these schemes compared to a naïve sampling scheme is demonstrated in both simulations and real data. Furthermore, we show that the weighted linear least squares (WLLS) estimator that uses the squared reciprocal of the noisy signal as weights can be biased, whereas the iteratively WLLS estimator with the squared reciprocal of the predicted signal as weights outperforms the conventional unweighted linear LS and nonlinear LS estimators in terms of accuracy and precision. Finally, we show that the use of appropriate constraints can considerably increase the precision of the estimator with only a limited decrease in accuracy.

ADEPT: Accurate Diffusion Echo-Planar imaging with multi-contrast shoTs.

PURPOSE: To introduce a novel imaging and parameter estimation framework for accurate multi-shot diffusion MRI. THEORY AND METHODS: We propose a new framework called ADEPT (Accurate Diffusion Echo-Planar imaging with multi-contrast shoTs) that enables fast diffusion MRI by allowing diffusion contrast settings to change between shots in a multi-shot EPI acquisition (i.e., intra-scan modulation). The framework estimates diffusion parameter maps directly from the acquired intra-scan modulated k-space data, while simultaneously accounting for shot-to-shot phase inconsistencies. The performance of the estimation framework is evaluated using Monte Carlo simulation studies and in-vivo experiments and compared to that of reference methods that rely on parallel imaging for shot-to-shot phase correction. RESULTS: Simulation and real-data experiments show that ADEPT yields more accurate and more precise estimates of the diffusion metrics in multi-shot EPI data in comparison with the reference methods. CONCLUSION: ADEPT allows fast multi-shot EPI diffusion MRI without significantly degrading the accuracy and precision of the estimated diffusion maps.

Automated mitral valve assessment for transcatheter mitral valve replacement planning.

Transcatheter mitral valve replacement (TMVR) has emerged as a minimally invasive alternative for treating patients suffering from mitral valve disease. The number of TMVR procedures is expected to rise as devices currently in clinical trials obtain approval for commercialization. Automating the planning of such interventions becomes, therefore, more relevant in an attempt to decrease inter-subject discrepancies and time spent in patient assessment. This study evaluates the performance of an automated method for detection of anatomical landmarks and generation of relevant measurements for device selection and positioning. Cardiac CT scans of 70 patients were collected retrospectively. Fifty scans were used to generate a statistical shape model (SSM) of the left heart chambers at ten different timepoints, whereas the remaining 20 scans were used for validation of the automated method. The clinical measurements resulting from the anatomical landmarks generated automatically were compared against the measurements obtained through the manual indication of the corresponding landmarks by three observers, during systole and diastole. The automatically generated measurements were in close agreement with the user-driven analysis, with intraclass correlation coefficients (ICC) consistently lower for the saddle-shaped (ICCArea = 0.90, ICCPerimeter 2D = 0.95, ICCPerimeter 3D = 0.93, ICCAP-Diameter = 0.71, ICCML-Diameter = 0.90) compared to the D-shaped annulus (ICCArea = 0.94, ICCPerimeter 2D = 0.96, ICCPerimeter 3D = 0.96, ICCAP-Diameter = 0.95, ICCML-Diameter = 0.92). The larger differences observed for the saddle shape suggest that the main discrepancies occur in the aorto-mitral curtain. This is supported by the fact that statistically significant differences are observed between the two annulus configurations for area (p < 0.001), 3D perimeter (p = 0.009) and AP diameter (p < 0.001), whereas errors for 2D perimeter and ML diameter remained almost constant. The mitral valve center deviated in average 2.5 mm from the user-driven position, a value comparable to the inter-observer variability. The present study suggests that accurate mitral valve assessment can be achieved with a fully automated method, what could result in more consistent and shorter pre-interventional planning of TMVR procedures.

Investigating Tissue-Specific Abnormalities in Alzheimer's Disease with Multi-Shell Diffusion MRI.

BACKGROUND: Most studies using diffusion-weighted MRI (DW-MRI) in Alzheimer's disease (AD) have focused their analyses on white matter (WM) microstructural changes using the diffusion (kurtosis) tensor model. Although recent works have addressed some limitations of the tensor model, such as the representation of crossing fibers and partial volume effects with cerebrospinal fluid (CSF), the focus remains in modeling and analyzing the WM. OBJECTIVE: In this work, we present a brain analysis approach for DW-MRI that disentangles multiple tissue compartments as well as micro- and macroscopic effects to investigate differences between groups of subjects in the AD continuum and controls. METHODS: By means of the multi-tissue constrained spherical deconvolution of multi-shell DW-MRI, underlying brain tissue is modeled with a WM fiber orientation distribution function along with the contributions of gray matter (GM) and CSF to the diffusion signal. From this multi-tissue model, a set of measures capturing tissue diffusivity properties and morphology are extracted. Group differences were interrogated following fixel-, voxel-, and tensor-based morphometry approaches while including strong FWE control across multiple comparisons. RESULTS: Abnormalities related to AD stages were detected in WM tracts including the splenium, cingulum, longitudinal fasciculi, and corticospinal tract. Changes in tissue composition were identified, particularly in the medial temporal lobe and superior longitudinal fasciculus. CONCLUSION: This analysis framework constitutes a comprehensive approach allowing simultaneous macro and microscopic assessment of WM, GM, and CSF, from a single DW-MRI dataset.

To shift or to rotate? Comparison of acquisition strategies for multi-slice super-resolution magnetic resonance imaging.

Multi-slice (MS) super-resolution reconstruction (SRR) methods have been proposed to improve the trade-off between resolution, signal-to-noise ratio and scan time in magnetic resonance imaging. MS-SRR consists in the estimation of an isotropic high-resolution image from a series of anisotropic MS images with a low through-plane resolution, where the anisotropic low-resolution images can be acquired according to different acquisition schemes. However, it is yet unclear how these schemes compare in terms of statistical performance criteria, especially for regularized MS-SRR. In this work, the estimation performance of two commonly adopted MS-SRR acquisition schemes based on shifted and rotated MS images respectively are evaluated in a Bayesian framework. The maximum a posteriori estimator, which introduces regularization by incorporating prior knowledge in a statistically well-defined way, is put forward as the estimator of choice and its accuracy, precision, and Bayesian mean squared error (BMSE) are used as performance criteria. Analytic calculations as well as Monte Carlo simulation experiments show that the rotated scheme outperforms the shifted scheme in terms of precision, accuracy, and BMSE. Furthermore, the superior performance of the rotated scheme is confirmed in real data experiments and in retrospective simulation experiments with and without inter-image motion. Results show that the rotated scheme allows regularized MS-SRR with a higher accuracy and precision than the shifted scheme, besides being more resilient to motion.

Virtual grating approach for Monte Carlo simulations of edge illumination-based x-ray phase contrast imaging.

The design of new x-ray phase contrast imaging setups often relies on Monte Carlo simulations for prospective parameter studies. Monte Carlo simulations are known to be accurate but time consuming, leading to long simulation times, especially when many parameter variations are required. This is certainly the case for imaging methods relying on absorbing masks or gratings, with various tunable properties, such as pitch, aperture size, and thickness. In this work, we present the virtual grating approach to overcome this limitation. By replacing the gratings in the simulation with virtual gratings, the parameters of the gratings can be changed after the simulation, thereby significantly reducing the overall simulation time. The method is validated by comparison to explicit grating simulations, followed by representative demonstration cases.

Automatic landmark detection and mapping for 2D/3D registration with BoneNet.

The 3D musculoskeletal motion of animals is of interest for various biological studies and can be derived from X-ray fluoroscopy acquisitions by means of image matching or manual landmark annotation and mapping. While the image matching method requires a robust similarity measure (intensity-based) or an expensive computation (tomographic reconstruction-based), the manual annotation method depends on the experience of operators. In this paper, we tackle these challenges by a strategic approach that consists of two building blocks: an automated 3D landmark extraction technique and a deep neural network for 2D landmarks detection. For 3D landmark extraction, we propose a technique based on the shortest voxel coordinate variance to extract the 3D landmarks from the 3D tomographic reconstruction of an object. For 2D landmark detection, we propose a customized ResNet18-based neural network, BoneNet, to automatically detect geometrical landmarks on X-ray fluoroscopy images. With a deeper network architecture in comparison to the original ResNet18 model, BoneNet can extract and propagate feature vectors for accurate 2D landmark inference. The 3D poses of the animal are then reconstructed by aligning the extracted 2D landmarks from X-ray radiographs and the corresponding 3D landmarks in a 3D object reference model. Our proposed method is validated on X-ray images, simulated from a real piglet hindlimb 3D computed tomography scan and does not require manual annotation of landmark positions. The simulation results show that BoneNet is able to accurately detect the 2D landmarks in simulated, noisy 2D X-ray images, resulting in promising rigid and articulated parameter estimations.

Model-based super-resolution reconstruction with joint motion estimation for improved quantitative MRI parameter mapping.

Quantitative Magnetic Resonance (MR) imaging provides reproducible measurements of biophysical parameters, and has become an essential tool in clinical MR studies. Unfortunately, 3D isotropic high resolution (HR) parameter mapping is hardly feasible in clinical practice due to prohibitively long acquisition times. Moreover, accurate and precise estimation of quantitative parameters is complicated by inevitable subject motion, the risk of which increases with scanning time. In this paper, we present a model-based super-resolution reconstruction (SRR) method that jointly estimates HR quantitative parameter maps and inter-image motion parameters from a set of 2D multi-slice contrast-weighted images with a low through-plane resolution. The method uses a Bayesian approach, which allows to optimally exploit prior knowledge of the tissue and noise statistics. To demonstrate its potential, the proposed SRR method is evaluated for a T1 and T2 quantitative mapping protocol. Furthermore, the method's performance in terms of precision, accuracy, and spatial resolution is evaluated using simulated as well as real brain imaging experiments. Results show that our proposed fully flexible, quantitative SRR framework with integrated motion estimation outperforms state-of-the-art SRR methods for quantitative MRI.

Improved diffusion parameter estimation by incorporating T2 relaxation properties into the DKI-FWE model.

The free water elimination (FWE) model and its kurtosis variant (DKI-FWE) can separate tissue and free water signal contributions, thus providing tissue-specific diffusional information. However, a downside of these models is that the associated parameter estimation problem is ill-conditioned, necessitating the use of advanced estimation techniques that can potentially bias the parameter estimates. In this work, we propose the T2-DKI-FWE model that exploits the T2 relaxation properties of both compartments, thereby better conditioning the parameter estimation problem and providing, at the same time, an additional potential biomarker (the T2 of tissue). In our approach, the T2 of tissue is estimated as an unknown parameter, whereas the T2 of free water is assumed known a priori and fixed to a literature value (1573 ms). First, the error propagation of an erroneous assumption on the T2 of free water is studied. Next, the improved conditioning of T2-DKI-FWE compared to DKI-FWE is illustrated using the Cramér-Rao lower bound matrix. Finally, the performance of the T2-DKI-FWE model is compared to that of the DKI-FWE and T2-DKI models on both simulated and real datasets. The error due to a biased approximation of the T2 of free water was found to be relatively small in various diffusion metrics and for a broad range of erroneous assumptions on its underlying ground truth value. Compared to DKI-FWE, using the T2-DKI-FWE model is beneficial for the identifiability of the model parameters. Our results suggest that the T2-DKI-FWE model can achieve precise and accurate diffusion parameter estimates, through effective reduction of free water partial volume effects and by using a standard nonlinear least squares approach. In conclusion, incorporating T2 relaxation properties into the DKI-FWE model improves the conditioning of the model fitting, while only requiring an acquisition scheme with at least two different echo times.