Tensor-valued diffusion MRI of human acute stroke.

PURPOSE: Tensor-valued diffusion encoding can disentangle orientation dispersion and subvoxel anisotropy, potentially offering insight into microstructural changes after cerebral ischemia. The purpose was to evaluate tensor-valued diffusion MRI in human acute ischemic stroke, assess potential confounders from diffusion time dependencies, and compare to Monte Carlo diffusion simulations of axon beading. METHODS: Linear (LTE) and spherical (STE) b-tensor encoding with inherently different effective diffusion times were acquired in 21 acute ischemic stroke patients between 3 and 57 h post-onset at 3 T in 2.5 min. In an additional 10 patients, STE with 2 LTE yielding different effective diffusion times were acquired for comparison. Diffusional variance decomposition (DIVIDE) was used to estimate microscopic anisotropy (µFA), as well as anisotropic, isotropic, and total diffusional variance (MKA , MKI , MKT ). DIVIDE parameters, and diffusion tensor imaging (DTI)-derived mean diffusivity and fractional anisotropy (FA) were compared in lesion versus contralateral white matter. Monte Carlo diffusion simulations of various cylindrical geometries for all b-tensor protocols were used to interpret parameter measurements. RESULTS: MD was ˜40% lower in lesions for all LTE/STE protocols. The DIVIDE parameters varied with effective diffusion time: higher µFA and MKA in lesion versus contralateral white matter for STE with longer effective diffusion time LTE, whereas the shorter effective diffusion time LTE protocol yielded lower µFA and MKA in lesions. Both protocols, regardless of diffusion time, were consistent with simulations of greater beading amplitude and intracellular volume fraction. CONCLUSION: DIVIDE parameters depend on diffusion time in acute stroke but consistently indicate neurite beading and larger intracellular volume fraction.

Human prostate MRI at ultrahigh-performance gradient: A feasibility study.

PURPOSE: To demonstrate the technical feasibility and the value of ultrahigh-performance gradient in imaging the prostate in a 3T MRI system. METHODS: In this local institutional review board-approved study, prostate MRI was performed on 4 healthy men. Each subject was scanned in a prototype 3T MRI system with a 42-cm inner-diameter gradient coil that achieves a maximum gradient amplitude of 200 mT/m and slew rate of 500 T/m/s. PI-RADS V2.1-compliant axial T2 -weighted anatomical imaging and single-shot echo planar DWI at standard gradient of 70 mT/m and 150 T/m/s were obtained, followed by DWI at maximum performance (i.e., 200 mT/m and 500 T/m/s). In comparison to state-of-the-art clinical whole-body MRI systems, the high slew rate improved echo spacing from 1020 to 596 µs and, together with a high gradient amplitude for diffusion encoding, TE was reduced from 55 to 36 ms. RESULTS: In all 4 subjects (waist circumference = 81-91 cm, age = 45-65 years), no peripheral nerve stimulation sensation was reported during DWI. Reduced image distortion in the posterior peripheral zone prostate gland and higher signal intensity, such as in the surrounding muscle of high-gradient DWI, were noted. CONCLUSION: Human prostate MRI at simultaneously high gradient amplitude of 200 mT/m and slew rate of 500 T/m/s is feasible, demonstrating that improved gradient performance can address image distortion and T2 decay-induced SNR issues for in vivo prostate imaging.

Tuned exchange imaging: Can the filter exchange imaging pulse sequence be adapted for applications with thin slices and restricted diffusion?

Filter exchange imaging (FEXI) is a double diffusion-encoding (DDE) sequence that is specifically sensitive to exchange between sites with different apparent diffusivities. FEXI uses a diffusion-encoding filtering block followed by a detection block at varying mixing times to map the exchange rate. Long mixing times enhance the sensitivity to exchange, but they pose challenges for imaging applications that require a stimulated echo sequence with crusher gradients. Thin imaging slices require strong crushers, which can introduce significant diffusion weighting and bias exchange rate estimates. Here, we treat the crushers as an additional encoding block and consider FEXI as a triple diffusion-encoding sequence. This allows the bias to be corrected in the case of multi-Gaussian diffusion, but not easily in the presence of restricted diffusion. Our approach addresses challenges in the presence of restricted diffusion and relies on the ability to independently gauge sensitivities to exchange and restricted diffusion for arbitrary gradient waveforms. It follows two principles: (i) the effects of crushers are included in the forward model using signal cumulant expansion; and (ii) timing parameters of diffusion gradients in filter and detection blocks are adjusted to maintain the same level of restriction encoding regardless of the mixing time. This results in the tuned exchange imaging (TEXI) protocol. The accuracy of exchange mapping with TEXI was assessed through Monte Carlo simulations in spheres of identical sizes and gamma-distributed sizes, and in parallel hexagonally packed cylinders. The simulations demonstrate that TEXI provides consistent exchange rates regardless of slice thickness and restriction size, even with strong crushers. However, the accuracy depends on b-values, mixing times, and restriction geometry. The constraints and limitations of TEXI are discussed, including suggestions for protocol adaptations. Further studies are needed to optimize the precision of TEXI and assess the approach experimentally in realistic, heterogeneous substrates.

Diffusion MRI with free gradient waveforms on a high-performance gradient system: Probing restriction and exchange in the human brain.

The dependence of the diffusion MRI signal on the diffusion time carries signatures of restricted diffusion and exchange. Here we seek to highlight these signatures in the human brain by performing experiments using free gradient waveforms designed to be selectively sensitive to the two effects. We examine six healthy volunteers using both strong and ultra-strong gradients (80, 200 and 300 mT/m). In an experiment featuring a large set of 150 gradient waveforms with different sensitivities to restricted diffusion and exchange, our results reveal unique and different time-dependence signatures in grey and white matter. Grey matter was characterised by both restricted diffusion and exchange and white matter predominantly by restricted diffusion. Exchange in grey matter was at least twice as fast as in white matter, across all subjects and all gradient strengths. The cerebellar cortex featured relatively short exchange times (115 ms). Furthermore, we show that gradient waveforms with tailored designs can be used to map exchange in the human brain. We also assessed the feasibility of clinical applications of the method used in this work and found that the exchange-related contrast obtained with a 25-minute protocol at 300 mT/m was preserved in a 4-minute protocol at 300 mT/m and a 10-minute protocol at 80 mT/m. Our work underlines the utility of free waveforms for detecting time dependence signatures due to restricted diffusion and exchange in vivo, which may potentially serve as a tool for studying diseased tissue.

Diffusion MRI with pulsed and free gradient waveforms: Effects of restricted diffusion and exchange.

Monitoring time dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted diffusion and exchange have opposite effects on the diffusion-weighted signal, which can lead to errors in parameter estimates. In this work, we propose a signal representation that incorporates the effects of both restricted diffusion and exchange up to second order in b-value and is compatible with gradient waveforms of arbitrary shape. The representation features mappings from a gradient waveform to two scalars that separately control the sensitivity to restriction and exchange. We demonstrate that these scalars span a two-dimensional space that can be used to choose waveforms that selectively probe restricted diffusion or exchange, eliminating the correlation between the two phenomena. We found that waveforms with specific but unconventional shapes provide an advantage over conventional pulsed and oscillating gradient acquisitions. We also show that parametrization of waveforms into a two-dimensional space can be used to understand protocols from other approaches that probe restricted diffusion and exchange. For example, we found that the variation of mixing time in filter-exchange imaging corresponds to variation of our exchange-weighting scalar at a fixed value of the restriction-weighting scalar. The proposed signal representation was evaluated using Monte Carlo simulations in identical parallel cylinders with hexagonal and random packing as well as parallel cylinders with gamma-distributed radii. Results showed that the approach is sensitive to sizes in the interval 4-12 µm and exchange rates in the simulated range of 0 to 20 s - 1 , but also that there is a sensitivity to the extracellular geometry. The presented theory constitutes a simple and intuitive description of how restricted diffusion and exchange influence the signal as well as a guide to protocol design capable of separating the two effects.

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Accelerating joint relaxation-diffusion MRI by integrating time division multiplexing and simultaneous multi-slice (TDM-SMS) strategies.

PURPOSE: To accelerate the acquisition of relaxation-diffusion imaging by integrating time-division multiplexing (TDM) with simultaneous multi-slice (SMS) for EPI and evaluate imaging quality and diffusion measures. METHODS: The time-division multiplexing (TDM) technique and SMS method were integrated to achieve a high slice-acceleration (e.g., 6×) factor for acquiring relaxation-diffusion MRI. Two variants of the sequence, referred to as TDM3e-SMS and TDM2s-SMS, were developed to simultaneously acquire slice groups with three distinct TEs and two slice groups with the same TE, respectively. Both sequences were evaluated on a 3T scanner with in vivo human brains and compared with standard single-band (SB) -EPI and SMS-EPI using diffusion measures and tractography results. RESULTS: Experimental results showed that the TDM3e-SMS sequence with total slice acceleration of 6 (multiplexing factor (MP) = 3 × multi-band factor (MB) = 2) provided similar image intensity and microstructure measures compared to standard SMS-EPI with MB = 2, and yielded less bias in intensity compared to standard SMS-EPI with MB = 4. The three sequences showed a similar positive correlation between TE and mean kurtosis (MK) and a negative correlation between TE and mean diffusivity (MD) in white matter. Multi-fiber tractography also shows consistency of results in TE-dependent measures between different sequences. The TDM2s-SMS sequence (MP = 2, MB = 2) also provided imaging measures similar to standard SMS-EPI sequences (MB = 2) for single-TE diffusion imaging. CONCLUSIONS: The TDM-SMS sequence can provide additional 2× to 3× acceleration to SMS without degrading imaging quality. With the significant reduction in scan time, TDM-SMS makes joint relaxation-diffusion MRI a feasible technique in neuroimaging research to investigate new markers of brain disorders.

Elucidating the relationship between white matter structure, demographic, and clinical variables in schizophrenia-a multicenter harmonized diffusion tensor imaging study.

White matter (WM) abnormalities are repeatedly demonstrated across the schizophrenia time-course. However, our understanding of how demographic and clinical variables interact, influence, or are dependent on WM pathologies is limited. The most well-known barriers to progress are heterogeneous findings due to small sample sizes and the confounding influence of age on WM. The present study leverages access to the harmonized diffusion magnetic-resonance-imaging data and standardized clinical data from 13 international sites (597 schizophrenia patients (SCZ)). Fractional anisotropy (FA) values for all major WM structures in patients were predicted based on FA models estimated from a healthy population (n = 492). We utilized the deviations between predicted and real FA values to answer three essential questions. (1) "Which clinical variables explain WM abnormalities?". (2) "Does the degree of WM abnormalities predict symptom severity?". (3) "Does sex influence any of those relationships?". Regression and mediator analyses revealed that a longer duration-of-illness is associated with more severe WM abnormalities in several tracts. In addition, they demonstrated that a higher antipsychotic medication dose is related to more severe corpus callosum abnormalities. A structural equation model revealed that patients with more WM abnormalities display higher symptom severity. Last, the results exhibited sex-specificity. Males showed a stronger association between duration-of-illness and WM abnormalities. Females presented a stronger association between WM abnormalities and symptom severity, with IQ impacting this relationship. Our findings provide clear evidence for the interaction of demographic, clinical, and behavioral variables with WM pathology in SCZ. Our results also point to the need for longitudinal studies, directly investigating the casualty and sex-specificity of these relationships, as well as the impact of cognitive resiliency on structure-function relationships.

Accuracy and precision in super-resolution MRI: Enabling spherical tensor diffusion encoding at ultra-high b-values and high resolution.

Diffusion MRI (dMRI) can probe the tissue microstructure but suffers from low signal-to-noise ratio (SNR) whenever high resolution is combined with high diffusion encoding strengths. Low SNR leads to poor precision as well as poor accuracy of the diffusion-weighted signal; the latter is caused by the rectified noise floor and can be observed as a positive bias in magnitude signal. Super-resolution techniques may facilitate a beneficial tradeoff between bias and resolution by allowing acquisition at low spatial resolution and high SNR, whereafter high spatial resolution is recovered by image reconstruction. In this work, we describe a super-resolution reconstruction framework for dMRI and investigate its performance with respect to signal accuracy and precision. Using phantom experiments and numerical simulations, we show that the super-resolution approach improves accuracy by facilitating a more beneficial trade-off between spatial resolution and diffusion encoding strength before the noise floor affects the signal. By contrast, precision is shown to have a less straightforward dependency on acquisition, reconstruction, and intrinsic tissue parameters. Indeed, we find a gain in precision from super-resolution reconstruction is substantial only when some spatial resolution is sacrificed. Finally, we deployed super-resolution reconstruction in a healthy brain for the challenging combination of spherical b-tensor encoding at ultra-high b-values and high spatial resolution-a configuration that produces a unique contrast that emphasizes tissue in which diffusion is restricted in all directions. This demonstration showcased that super-resolution reconstruction enables a vastly superior image contrast compared to conventional imaging, facilitating investigations that would otherwise have prohibitively low SNR, resolution or require non-conventional MRI hardware.

Diffusion-informed spatial smoothing of fMRI data in white matter using spectral graph filters.

Brain activation mapping using functional magnetic resonance imaging (fMRI) has been extensively studied in brain gray matter (GM), whereas in large disregarded for probing white matter (WM). This unbalanced treatment has been in part due to controversies in relation to the nature of the blood oxygenation level-dependent (BOLD) contrast in WM and its detectability. However, an accumulating body of studies has provided solid evidence of the functional significance of the BOLD signal in WM and has revealed that it exhibits anisotropic spatio-temporal correlations and structure-specific fluctuations concomitant with those of the cortical BOLD signal. In this work, we present an anisotropic spatial filtering scheme for smoothing fMRI data in WM that accounts for known spatial constraints on the BOLD signal in WM. In particular, the spatial correlation structure of the BOLD signal in WM is highly anisotropic and closely linked to local axonal structure in terms of shape and orientation, suggesting that isotropic Gaussian filters conventionally used for smoothing fMRI data are inadequate for denoising the BOLD signal in WM. The fundamental element in the proposed method is a graph-based description of WM that encodes the underlying anisotropy observed across WM, derived from diffusion-weighted MRI data. Based on this representation, and leveraging graph signal processing principles, we design subject-specific spatial filters that adapt to a subject's unique WM structure at each position in the WM that they are applied at. We use the proposed filters to spatially smooth fMRI data in WM, as an alternative to the conventional practice of using isotropic Gaussian filters. We test the proposed filtering approach on two sets of simulated phantoms, showcasing its greater sensitivity and specificity for the detection of slender anisotropic activations, compared to that achieved with isotropic Gaussian filters. We also present WM activation mapping results on the Human Connectome Project's 100-unrelated subject dataset, across seven functional tasks, showing that the proposed method enables the detection of streamline-like activations within axonal bundles.

Q-space trajectory imaging with positivity constraints (QTI+).

Q-space trajectory imaging (QTI) enables the estimation of useful scalar measures indicative of the local tissue structure. This is accomplished by employing generalized gradient waveforms for diffusion sensitization alongside a diffusion tensor distribution (DTD) model. The first two moments of the underlying DTD are made available by acquisitions at low diffusion sensitivity (b-values). Here, we show that three independent conditions have to be fulfilled by the mean and covariance tensors associated with distributions of symmetric positive semidefinite tensors. We introduce an estimation framework utilizing semi-definite programming (SDP) to guarantee that these conditions are met. Applying the framework on simulated signal profiles for diffusion tensors distributed according to non-central Wishart distributions demonstrates the improved noise resilience of QTI+ over the commonly employed estimation methods. Our findings on a human brain data set also reveal pronounced improvements, especially so for acquisition protocols featuring few number of volumes. Our method's robustness to noise is expected to not only improve the accuracy of the estimates, but also enable a meaningful interpretation of contrast in the derived scalar maps. The technique's performance on shorter acquisitions could make it feasible in routine clinical practice.

Neural networks for parameter estimation in microstructural MRI: Application to a diffusion-relaxation model of white matter.

Specific features of white matter microstructure can be investigated by using biophysical models to interpret relaxation-diffusion MRI brain data. Although more intricate models have the potential to reveal more details of the tissue, they also incur time-consuming parameter estimation that may converge to inaccurate solutions due to a prevalence of local minima in a degenerate fitting landscape. Machine-learning fitting algorithms have been proposed to accelerate the parameter estimation and increase the robustness of the attained estimates. So far, learning-based fitting approaches have been restricted to microstructural models with a reduced number of independent model parameters where dense sets of training data are easy to generate. Moreover, the degree to which machine learning can alleviate the degeneracy problem is poorly understood. For conventional least-squares solvers, it has been shown that degeneracy can be avoided by acquisition with optimized relaxation-diffusion-correlation protocols that include tensor-valued diffusion encoding. Whether machine-learning techniques can offset these acquisition requirements remains to be tested. In this work, we employ artificial neural networks to vastly accelerate the parameter estimation for a recently introduced relaxation-diffusion model of white matter microstructure. We also develop strategies for assessing the accuracy and sensitivity of function fitting networks and use those strategies to explore the impact of the acquisition protocol. The developed learning-based fitting pipelines were tested on relaxation-diffusion data acquired with optimal and sub-optimal acquisition protocols. Networks trained with an optimized protocol were observed to provide accurate parameter estimates within short computational times. Comparing neural networks and least-squares solvers, we found the performance of the former to be less affected by sub-optimal protocols; however, model fitting networks were still susceptible to degeneracy issues and their use could not fully replace a careful design of the acquisition protocol.

Deep learning based segmentation of brain tissue from diffusion MRI.

Segmentation of brain tissue types from diffusion MRI (dMRI) is an important task, required for quantification of brain microstructure and for improving tractography. Current dMRI segmentation is mostly based on anatomical MRI (e.g., T1- and T2-weighted) segmentation that is registered to the dMRI space. However, such inter-modality registration is challenging due to more image distortions and lower image resolution in dMRI as compared with anatomical MRI. In this study, we present a deep learning method for diffusion MRI segmentation, which we refer to as DDSeg. Our proposed method learns tissue segmentation from high-quality imaging data from the Human Connectome Project (HCP), where registration of anatomical MRI to dMRI is more precise. The method is then able to predict a tissue segmentation directly from new dMRI data, including data collected with different acquisition protocols, without requiring anatomical data and inter-modality registration. We train a convolutional neural network (CNN) to learn a tissue segmentation model using a novel augmented target loss function designed to improve accuracy in regions of tissue boundary. To further improve accuracy, our method adds diffusion kurtosis imaging (DKI) parameters that characterize non-Gaussian water molecule diffusion to the conventional diffusion tensor imaging parameters. The DKI parameters are calculated from the recently proposed mean-kurtosis-curve method that corrects implausible DKI parameter values and provides additional features that discriminate between tissue types. We demonstrate high tissue segmentation accuracy on HCP data, and also when applying the HCP-trained model on dMRI data from other acquisitions with lower resolution and fewer gradient directions.

SNR-enhanced diffusion MRI with structure-preserving low-rank denoising in reproducing kernel Hilbert spaces.

PURPOSE: To introduce, develop, and evaluate a novel denoising technique for diffusion MRI that leverages nonlinear redundancy in the data to boost the SNR while preserving signal information. METHODS: We exploit nonlinear redundancy of the dMRI data by means of kernel principal component analysis (KPCA), a nonlinear generalization of PCA to reproducing kernel Hilbert spaces. By mapping the signal to a high-dimensional space, a higher level of redundant information is exploited, thereby enabling better denoising than linear PCA. We implement KPCA with a Gaussian kernel, with parameters automatically selected from knowledge of the noise statistics, and validate it on realistic Monte Carlo simulations as well as with in vivo human brain submillimeter and low-resolution dMRI data. We also demonstrate KPCA denoising on multi-coil dMRI data. RESULTS: SNR improvements up to 2.7 × were obtained in real in vivo datasets denoised with KPCA, in comparison to SNR gains of up to 1.8 × using a linear PCA denoising technique called Marchenko-Pastur PCA (MPPCA). Compared to gold-standard dataset references created from averaged data, we showed that lower normalized root mean squared error was achieved with KPCA compared to MPPCA. Statistical analysis of residuals shows that anatomical information is preserved and only noise is removed. Improvements in the estimation of diffusion model parameters such as fractional anisotropy, mean diffusivity, and fiber orientation distribution functions were also demonstrated. CONCLUSION: Nonlinear redundancy of the dMRI signal can be exploited with KPCA, which allows superior noise reduction/SNR improvements than the MPPCA method, without loss of signal information.

Mapping prostatic microscopic anisotropy using linear and spherical b-tensor encoding: A preliminary study.

PURPOSE: Tensor-valued diffusion encoding provides more specific information than conventional diffusion-weighted imaging (DWI), but has mainly been applied in neuroimaging studies. This study aimed to assess its potential for the imaging of prostate cancer (PCa). METHODS: Seventeen patients with histologically proven PCa were enrolled. DWI of the prostate was performed with linear and spherical tensor encoding using a maximal b-value of 1.5 ms/µm2 and a voxel size of 3 × 3 × 4 mm3 . The gamma-distribution model was used to estimate the mean diffusivity (MD), the isotropic kurtosis (MKI ), and the anisotropic kurtosis (MKA ). Regions of interest were placed in MR-defined cancerous tissues, as well as in apparently healthy tissues in the peripheral and transitional zones (PZs and TZs). RESULTS: DWI with linear and spherical encoding yielded different image contrasts at high b-values, which enabled the estimation of MKA and MKI . Compared with healthy tissue (PZs and TZs combined) the cancers displayed a significantly lower MD (P < .05), higher MKI (P < 10-5 ), and lower MKA (P < .05). Compared with the TZ, tissue in the PZ showed lower MD (P < 10-3 ) and higher MKA (P < 10-3 ). No significant differences were found between cancers of different Gleason scores, possibly because of the limited sample size. CONCLUSION: Tensor-valued diffusion encoding enabled mapping of MKA and MKI in the prostate. The elevated MKI in PCa compared with normal tissues suggests an elevated heterogeneity in the cancers. Increased in-plane resolution could improve tumor delineation in future studies.

Motion-compensated gradient waveforms for tensor-valued diffusion encoding by constrained numerical optimization.

PURPOSE: Diffusion-weighted MRI is sensitive to incoherent tissue motion, which may confound the measured signal and subsequent analysis. We propose a "motion-compensated" gradient waveform design for tensor-valued diffusion encoding that negates the effects bulk motion and incoherent motion in the ballistic regime. METHODS: Motion compensation was achieved by constraining the magnitude of gradient waveform moment vectors. The constraint was incorporated into a numerical optimization framework, along with existing constraints that account for b-tensor shape, hardware restrictions, and concomitant field gradients. We evaluated the efficacy of encoding and motion compensation in simulations, and we demonstrated the approach by linear and planar b-tensor encoding in a healthy heart in vivo. RESULTS: The optimization framework produced asymmetric motion-compensated waveforms that yielded b-tensors of arbitrary shape with improved efficiency compared with previous designs for tensor-valued encoding, and equivalent efficiency to previous designs for linear (conventional) encoding. Technical feasibility was demonstrated in the heart in vivo, showing vastly improved data quality when using motion compensation. The optimization framework is available online in open source. CONCLUSION: Our gradient waveform design is both more flexible and efficient than previous methods, facilitating tensor-valued diffusion encoding in tissues in which motion would otherwise confound the signal. The proposed design exploits asymmetric encoding times, a single refocusing pulse or multiple refocusing pulses, and integrates compensation for concomitant gradient effects throughout the imaging volume.

Combined diffusion-relaxometry microstructure imaging: Current status and future prospects.

Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article reviews an emerging paradigm that has the potential to provide a more detailed assessment of tissue microstructure-combined diffusion-relaxometry imaging. Combined diffusion-relaxometry acquisitions vary multiple MR contrast encodings-such as b-value, gradient direction, inversion time, and echo time-in a multidimensional acquisition space. When paired with suitable analysis techniques, this enables quantification of correlations and coupling between multiple MR parameters-such as diffusivity, T1 , T2 , and T2∗ . This opens the possibility of disentangling multiple tissue compartments (within voxels) that are indistinguishable with single-contrast scans, enabling a new generation of microstructural maps with improved biological sensitivity and specificity.

Towards unconstrained compartment modeling in white matter using diffusion-relaxation MRI with tensor-valued diffusion encoding.

PURPOSE: To optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T2 values within a two-compartment model of white matter, and to explore the approach in vivo. METHODS: Sampling protocols featuring different b-values (b), b-tensor shapes (bΔ ), and echo times (TE) were optimized using Cramér-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T2 values were estimated in a model featuring two microstructural compartments represented by a "stick" and a "zeppelin." RESULTS: Precise parameter estimates were enabled by sampling protocols featuring seven or more "shells" with unique b/bΔ /TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the "stick" compartment had a fraction of approximately 0.5 and, compared with the "zeppelin" compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 µm2 /ms) but higher T2 values (85 vs. 65 ms). Children featured lower "stick" fractions (0.4). White matter lesions exhibited high "zeppelin" isotropic diffusivities (1.7 µm2 /ms) and T2 values (150 ms). CONCLUSIONS: Diffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.

Tensor-valued diffusion MRI in under 3 minutes: an initial survey of microscopic anisotropy and tissue heterogeneity in intracranial tumors.

PURPOSE: To evaluate the feasibility of a 3-minutes protocol for assessment of the microscopic anisotropy and tissue heterogeneity based on tensor-valued diffusion MRI in a wide range of intracranial tumors. METHODS: B-tensor encoding was performed in 42 patients with intracranial tumors (gliomas, meningiomas, adenomas, and metastases). Microscopic anisotropy and tissue heterogeneity were evaluated by estimating the anisotropic kurtosis (MKA ) and isotropic kurtosis (MKI ), respectively. An extensive imaging protocol was compared with a 3-minutes protocol. RESULTS: The fast imaging protocol yielded parameters with characteristics in terms of bias and precision similar to the full protocol. Glioblastomas had lower microscopic anisotropy than meningiomas (MKA = 0.29 ± 0.06 vs. 0.45 ± 0.08, P = 0.003). Metastases had higher tissue heterogeneity (MKI = 0.57 ± 0.07) than both the glioblastomas (0.44 ± 0.06, P < 0.001) and meningiomas (0.46 ± 0.06, P = 0.03). CONCLUSION: Evaluation of the microscopic anisotropy and tissue heterogeneity in intracranial tumor patients is feasible in clinically relevant times frames.

Fast and accurate initialization of the free-water imaging model parameters from multi-shell diffusion MRI.

Cerebrospinal fluid partial volume effect is a known bias in the estimation of Diffusion Tensor Imaging (DTI) parameters from diffusion MRI data. The Free-Water Imaging model for diffusion MRI data adds a second compartment to the DTI model, which explicitly accounts for the signal contribution of extracellular free-water, such as cerebrospinal fluid. As a result the DTI parameters obtained through the free-water model are corrected for partial volume effects, and thus better represent tissue microstructure. In addition, the model estimates the fractional volume of free-water, and can be used to monitor changes in the extracellular space. Under certain assumptions, the model can be estimated from single-shell diffusion MRI data. However, by using data from multi-shell diffusion acquisitions, these assumptions can be relaxed, and the fit becomes more robust. Nevertheless, fitting the model to multi-shell data requires high computational cost, with a non-linear iterative minimization, which has to be initialized close enough to the global minimum to avoid local minima and to robustly estimate the model parameters. Here we investigate the properties of the main initialization approaches that are currently being used, and suggest new fast approaches to improve the initial estimates of the model parameters. We show that our proposed approaches provide a fast and accurate initial approximation of the model parameters, which is very close to the final solution. We demonstrate that the proposed initializations improve the final outcome of non-linear model fitting.