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Purpose: The compartmental nature of brain tissue microstructure is typically studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI relies on signal representations or biophysical models, while MR relaxometry and correlation studies are based on regularized inverse Laplace transforms (ILTs). Here we introduce a general framework for characterizing microstructure that does not depend on diffusion modeling and replaces ill-posed ILTs with blind source separation (BSS). This framework yields proton density, relaxation times, volume fractions, and signal disentanglement, allowing for separation of the free-water component., Theory and Methods: Diffusion experiments repeated for several different echo times, contain entangled diffusion and relaxation compartmental information. These can be disentangled by BSS using a physically constrained nonnegative matrix factorization., Results: Computer simulations, phantom studies, together with repeatability and reproducibility experiments demonstrated that BSS is capable of estimating proton density, compartmental volume fractions and transversal relaxations. In vivo results proved its potential to correct for free-water contamination and to estimate tissue parameters., Conclusion: Formulation of the diffusion-relaxation dependence as a BSS problem introduces a new framework for studying microstructure compartmentalization, and a novel tool for free-water elimination., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: Diffusion MRI often suffers from low signal-to-noise ratio, especially for high b-values. This work proposes a model-based denoising technique to address this limitation., Methods: A generalization of the multi-shell spherical deconvolution model using a Richardson-Lucy algorithm is applied to noisy data. The reconstructed coefficients are then used in the forward model to compute denoised diffusion-weighted images (DWIs). The proposed method operates in the diffusion space and thus is complementary to image-based denoising methods., Results: We demonstrate improved image quality on the DWIs themselves, maps of neurite orientation dispersion and density imaging, and diffusional kurtosis imaging (DKI), as well as reduced spurious peaks in deterministic tractography. For DKI in particular, we observe up to 50% error reduction and demonstrate high image quality using just 30 DWIs. This corresponds to greater than fourfold reduction in scan time if compared to the widely used 140-DWI acquisitions. We also confirm consistent performance in pathological data sets, namely in white matter lesions of a multiple sclerosis patient., Conclusion: The proposed denoising technique termed generalized spherical deconvolution has the potential of significantly improving image quality in diffusion MRI. Magn Reson Med 78:2428-2438, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To compare the effectiveness of prospective, retrospective, and combined (prospective + retrospective) EPI distortion correction methods in bilateral breast diffusion-weighted imaging (DWI) scans., Methods: Five healthy female subjects underwent an axial bilateral breast DWI exam with and without prospective B 0 inhomogeneity correction using slice-by-slice linear shimming. In each case, an additional b=0 DWI scan was performed with the polarity of the phase-encoding gradient reversed, to generate an estimated B 0 map; this map or a separately acquired B 0 map was used for retrospective correction, either alone or in combination with the prospective correction. The alignment between an undistorted, anatomical reference scan with similar contrast and the corrected b=0 DWI images with different correction schemes was assessed., Results: The average cross-correlation coefficient between the DWI images and the anatomical reference scan was increased from 0.82 to 0.92 over the five volunteers when combined prospective and retrospective distortion correction was applied. Furthermore, such correction substantially reduced patient-to-patient variation of the image alignment and the variability of the average apparent diffusion coefficient in normal glandular tissue., Conclusion: Combined prospective and retrospective distortion correction can provide an efficient way to reduce susceptibility-induced image distortions and enhance the reliability of breast DWI exams. Magn Reson Med 78:247-253, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: Because of the intrinsic low signal-to-noise ratio in diffusion-weighted imaging (DWI), magnitude processing often causes an overestimation of the signal's amplitude. This results in low-estimation accuracy of diffusion models and reduced contrast because of a superposition of the image signal and the noise floor. We adopt a new phase correction (PC) technique that yields real valued diffusion data while maintaining a Gaussian noise distribution., Methods: We conduct simulations of the noise propagation in the echo-planar imaging reconstruction chain to determine the spatial noise correlation in the image. Using the correlation pattern, optimized filter kernels are derived to estimate the true phase of the signal in each voxel. Furthermore, we adopt an outlier detection technique to replace the real value by the magnitude in case of substantial signal loss resulting from incorrect PC., Results: The benefits of our method are demonstrated on Monte Carlo simulations, DWI data acquired from healthy volunteer experiments, estimated parameters of the diffusion kurtosis imaging model, and the model-free diffusion spectrum imaging technique. The improved PC approach significantly reduces the noise bias and only slightly increases the sensitivity to local phase variations., Conclusion: PC can enhance the usefulness of higher b-values, allowing deeper insights into tissue microstructure. Magn Reson Med 77:559-570, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: Diffusion spectrum imaging (DSI) is an imaging technique that has been successfully applied to resolve white matter crossings in the human brain. However, its accuracy in complex microstructure environments has not been well characterized., Theory and Methods: Here we have simulated different tissue configurations, sampling schemes, and processing steps to evaluate DSI performances' under realistic biophysical conditions. A novel approach to compute the orientation distribution function (ODF) has also been developed to include biophysical constraints, namely integration ranges compatible with axial fiber diffusivities., Results: Performed simulations identified several DSI configurations that consistently show aliasing artifacts caused by fast diffusion components for both isotropic diffusion and fiber configurations. The proposed method for ODF computation showed some improvement in reducing such artifacts and improving the ability to resolve crossings, while keeping the quantitative nature of the ODF., Conclusion: In this study, we identified an important limitation of current DSI implementations, specifically the presence of aliasing due to fast diffusion components like those from pathological tissues, which are not well characterized, and can lead to artifactual fiber reconstructions. To minimize this issue, a new way of computing the ODF was introduced, which removes most of these artifacts and offers improved angular resolution. Magn Reson Med 76:1837-1847, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Diffusional kurtosis imaging (DKI) is an approach to characterizing the non-Gaussian fraction of water diffusion in biological tissue. However, DKI is highly susceptible to the low signal-to-noise ratio of diffusion-weighted images, causing low precision and a significant bias due to Rician noise distribution. Here, we evaluate precision and bias using weighted linear least squares fitting of different acquisition schemes including several multishell schemes, a diffusion spectrum imaging (DSI) scheme, as well as a compressed sensing reconstruction of undersampled DSI scheme., Methods: Monte Carlo simulations were performed to study the three-dimensional distribution of the apparent kurtosis coefficient (AKC). Experimental data were acquired from one healthy volunteer with multiple repetitions, using the same acquisition schemes as for the simulations., Results: The angular distribution of the bias and precision were very inhomogeneous. While axial kurtosis was significantly overestimated, radial kurtosis was underestimated. The precision of radial kurtosis was up to 10-fold lower than axial kurtosis., Conclusion: The noise bias behavior of DKI is highly complex and can cause overestimation as well as underestimation of the AKC even within one voxel. The acquisition scheme with three shells, suggested by Poot et al, provided overall the best performance. Magn Reson Med 76:1684-1696, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Within the last decade hyperpolarized [1-13C] pyruvate chemical-shift imaging has demonstrated impressive potential for metabolic MR imaging for a wide range of applications in oncology, cardiology, and neurology. In this work, a highly efficient pulse sequence is described for time-resolved, multislice chemical shift imaging of the injected substrate and obtained downstream metabolites. Using spectral-spatial excitation in combination with single-shot spiral data acquisition, the overall encoding is evenly distributed between excitation and signal reception, allowing the encoding of one full two-dimensional metabolite image per excitation. The signal-to-noise ratio can be flexibly adjusted and optimized using lower flip angles for the pyruvate substrate and larger ones for the downstream metabolites. Selectively adjusting the excitation of the down-stream metabolites to 90° leads to a so-called "saturation-recovery" scheme with the detected signal content being determined by forward conversion of the available pyruvate. In case of repetitive excitations, the polarization is preserved using smaller flip angles for pyruvate. Metabolic exchange rates are determined spatially resolved from the metabolite images using a simplified two-site exchange model. This novel contrast is an important step toward more quantitative metabolic imaging. Goal of this work was to derive, analyze, and implement this "saturation-recovery metabolic exchange rate imaging" and demonstrate its capabilities in four rats bearing subcutaneous tumors., (Copyright © 2012 Wiley Periodicals, Inc.)

We developed a novel method to accelerate diffusion spectrum imaging using compressed sensing. The method can be applied to either reduce acquisition time of diffusion spectrum imaging acquisition without losing critical information or to improve the resolution in diffusion space without increasing scan time. Unlike parallel imaging, compressed sensing can be applied to reconstruct a sub-Nyquist sampled dataset in domains other than the spatial one. Simulations of fiber crossings in 2D and 3D were performed to systematically evaluate the effect of compressed sensing reconstruction with different types of undersampling patterns (random, gaussian, Poisson disk) and different acceleration factors on radial and axial diffusion information. Experiments in brains of healthy volunteers were performed, where diffusion space was undersampled with different sampling patterns and reconstructed using compressed sensing. Essential information on diffusion properties, such as orientation distribution function, diffusion coefficient, and kurtosis is preserved up to an acceleration factor of R = 4., (Copyright © 2011 Wiley Periodicals, Inc.)