Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences.

A major challenge in understanding the cellular diversity of the brain has been linking activity during behavior with standard cellular typology. For example, it has not been possible to determine whether principal neurons in prefrontal cortex active during distinct experiences represent separable cell types, and it is not known whether these differentially active cells exert distinct causal influences on behavior. Here, we develop quantitative hydrogel-based technologies to connect activity in cells reporting on behavioral experience with measures for both brain-wide wiring and molecular phenotype. We find that positive and negative-valence experiences in prefrontal cortex are represented by cell populations that differ in their causal impact on behavior, long-range wiring, and gene expression profiles, with the major discriminant being expression of the adaptation-linked gene NPAS4. These findings illuminate cellular logic of prefrontal cortex information processing and natural adaptive behavior and may point the way to cell-type-specific understanding and treatment of disease-associated states.

An orexigenic subnetwork within the human hippocampus.

Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1-4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

Quantitative MRI reveals widespread, network-specific myelination change during generalized epilepsy progression.

Activity-dependent myelination is a fundamental mode of brain plasticity which significantly influences network function. We recently discovered that absence seizures, which occur in multiple forms of generalized epilepsy, can induce activity-dependent myelination, which in turn promotes further progression of epilepsy. Structural alterations of myelin are likely to be widespread, given that absence seizures arise from an extensive thalamocortical network involving frontoparietal regions of the bilateral hemispheres. However, the temporal course and spatial extent of myelin plasticity is unknown, due to limitations of gold-standard histological methods such as electron microscopy (EM). In this study, we leveraged magnetization transfer and diffusion MRI for estimation of g-ratios across major white matter tracts in a mouse model of generalized epilepsy with progressive absence seizures. EM was performed on the same brains after MRI. After seizure progression, we found increased myelination (decreased g-ratios) throughout the anterior portion (genu-to-body) of the corpus callosum but not in the posterior portion (body-splenium) nor in the fornix or the internal capsule. Curves obtained from averaging g-ratio values at every longitudinal point of the corpus callosum were statistically different with p<0.001. Seizure-associated myelin differences found in the corpus callosum body with MRI were statistically significant (p = 0.0027) and were concordant with EM in the same region (p = 0.01). Notably, these differences were not detected by diffusion tensor imaging. This study reveals widespread myelin structural change that is specific to the absence seizure network. Furthermore, our findings demonstrate the potential utility and importance of MRI-based g-ratio estimation to non-invasively detect myelin plasticity.

Frequency-dependent diffusion kurtosis imaging in the human brain using an oscillating gradient spin echo sequence and a high-performance head-only gradient.

Measuring the time/frequency dependence of diffusion MRI is a promising approach to distinguish between the effects of different tissue microenvironments, such as membrane restriction, tissue heterogeneity, and compartmental water exchange. In this study, we measure the frequency dependence of diffusivity (D) and kurtosis (K) with oscillating gradient diffusion encoding waveforms and a diffusion kurtosis imaging (DKI) model in human brains using a high-performance, head-only MAGNUS gradient system, with a combination of b-values, oscillating frequencies (f), and echo time that has not been achieved in human studies before. Frequency dependence of diffusivity and kurtosis are observed in both global and local white matter (WM) and gray matter (GM) regions and characterized with a power-law model ∼Λ*fθ. The frequency dependences of diffusivity and kurtosis (including changes between fmin and fmax, Λ, and θ) vary over different WM and GM regions, indicating potential microstructural differences between regions. A trend of decreasing kurtosis over frequency in the short-time limit is successfully captured for in vivo human brains. The effects of gradient nonlinearity (GNL) on frequency-dependent diffusivity and kurtosis measurements are investigated and corrected. Our results show that the GNL has prominent scaling effects on the measured diffusivity values (3.5∼5.5% difference in the global WM and 6∼8% difference in the global cortex) and subsequently affects the corresponding power-law parameters (Λ, θ) while having a marginal influence on the measured kurtosis values (<0.05% difference) and power-law parameters (Λ, θ). This study expands previous OGSE studies and further demonstrates the translatability of frequency-dependent diffusivity and kurtosis measurements to human brains, which may provide new opportunities to probe human brain microstructure in health and disease.

Multi-band multi-shot diffusion MRI reconstruction with joint usage of structured low-rank constraints and explicit phase mapping.

PURPOSE: To develop a joint reconstruction method for multi-band multi-shot diffusion MRI. THEORY AND METHODS: Multi-band multi-shot EPI acquisition is an effective approach for high-resolution diffusion MRI, but requires specific algorithms to correct the inter-shot phase variations. The phase correction can be done by first estimating the explicit phase map and then feeding it into the k-space signal formulation model. Alternatively, the phase information can be used indirectly as structured low-rank constraints in k-space. The 2 methods differ in reconstruction accuracy and efficiency. We aim to combine the 2 different approaches for improved image quality and reconstruction efficiency simultaneously, termed "joint usage of structured low-rank constraints and explicit phase mapping" (JULEP). The proposed JULEP reconstruction is tested on both single-band and multi-band, multi-shot diffusion data, with different resolutions and b values. The results of JULEP are compared with conventional methods with explicit phase mapping (i.e., multiplexed sensitivity-encoding [MUSE]) and structured low-rank constraints (i.e., MUSSELS), and another joint reconstruction method (i.e., network estimated artifacts for tempered reconstruction [NEATR]). RESULTS: JULEP improves the quality of the navigator and subsequently facilitates the reconstruction of final diffusion images. Compared with all 3 other methods (MUSE, MUSSELS, and NEATR), JULEP mitigates residual structural bias and improves temporal SNRs in the final diffusion image, particularly at high multi-band factors. Compared with MUSSELS, JULEP also improves computational efficiency. CONCLUSION: The proposed JULEP method significantly improves the image quality and reconstruction efficiency of multi-band multi-shot diffusion MRI, which can promote a broader application of high-resolution diffusion MRI.

Aberrant impulse control circuitry in obesity.

The ventromedial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) circuit has been implicated in impulsive reward-seeking. This disinhibition has been implicated in obesity and often manifests as binge eating, which is associated with worse treatment outcomes and comorbidities. It remains unclear whether the vmPFC-NAc circuit is perturbed in impulsive eaters with obesity. Initially, we analyzed publicly available, high-resolution, normative imaging data to localize where vmPFC structural connections converged within the NAc. These structural connections were found to converge ventromedially in the presumed NAc shell subregion. We then analyzed multimodal clinical and imaging data to test the a priori hypothesis that the vmPFC-NAc shell circuit is linked to obesity in a sample of female participants that regularly engaged in impulsive eating (i.e., binge eating). Functionally, vmPFC-NAc shell resting-state connectivity was inversely related to body mass index (BMI) and decreased in the obese state. Structurally, vmPFC-NAc shell structural connectivity and vmPFC thickness were inversely correlated with BMI; obese binge-prone participants exhibited decreased vmPFC-NAc structural connectivity and vmPFC thickness. Finally, to examine a causal link to binge eating, we directly probed this circuit in one binge-prone obese female using NAc deep brain stimulation in a first-in-human trial. Direct stimulation of the NAc shell subregion guided by local behaviorally relevant electrophysiology was associated with a decrease in number of weekly episodes of uncontrolled eating and decreased BMI. This study unraveled vmPFC-NAc shell circuit aberrations in obesity that can be modulated to restore control over eating behavior in obesity.

Oscillating diffusion-encoding with a high gradient-amplitude and high slew-rate head-only gradient for human brain imaging.

PURPOSE: We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate). METHODS: Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm2 . Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom. RESULTS: Simulations show that to achieve high frequency and b-value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8-19%, radial: 9-27%, parallel: 8-15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short-range disorder model provided radial long-term diffusivities of D∞,MD = 911 ± 72 µm2 /s, D∞,PD = 1519 ± 164 µm2 /s, and D∞,RD = 640 ± 111 µm2 /s and correlation lengths of lc,MD = 0.802 ± 0.156 µm, lc,PD = 0.837 ± 0.172 µm, and lc,RD = 0.780 ± 0.174 µm. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected. CONCLUSION: The high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head-gradient enables OGSE acquisition for in vivo human brain imaging.

Generalized diffusion spectrum magnetic resonance imaging (GDSI) for model-free reconstruction of the ensemble average propagator.

Diffusion spectrum MRI (DSI) provides model-free estimation of the diffusion ensemble average propagator (EAP) and orientation distribution function (ODF) but requires the diffusion data to be acquired on a Cartesian q-space grid. Multi-shell diffusion acquisitions are more flexible and more commonly acquired but have, thus far, only been compatible with model-based analysis methods. Here, we propose a generalized DSI (GDSI) framework to recover the EAP from multi-shell diffusion MRI data. The proposed GDSI approach corrects for q-space sampling density non-uniformity using a fast geometrical approach. The EAP is directly calculated in a preferable coordinate system by multiplying the sampling density corrected q-space signals by a discrete Fourier transform matrix, without any need for gridding. The EAP is demonstrated as a way to map diffusion patterns in brain regions such as the thalamus, cortex and brainstem where the tissue microstructure is not as well characterized as in white matter. Scalar metrics such as the zero displacement probability and displacement distances at different fractions of the zero displacement probability were computed from the recovered EAP to characterize the diffusion pattern within each voxel. The probability averaged across directions at a specific displacement distance provides a diffusion property based image contrast that clearly differentiates tissue types. The displacement distance at the first zero crossing of the EAP averaged across directions orthogonal to the primary fiber orientation in the corpus callosum is found to be larger in the body (5.65 ±â€¯0.09 µm) than in the genu (5.55 ±â€¯0.15 µm) and splenium (5.4 ±â€¯0.15 µm) of the corpus callosum, which corresponds well to prior histological studies. The EAP also provides model-free representations of angular structure such as the diffusion ODF, which allows estimation and comparison of fiber orientations from both the model-free and model-based methods on the same multi-shell data. For the model-free methods, detection of crossing fibers is found to be strongly dependent on the maximum b-value and less sensitive compared to the model-based methods. In conclusion, our study provides a generalized DSI approach that allows flexible reconstruction of the diffusion EAP and ODF from multi-shell diffusion data and data acquired with other sampling patterns.

Multimodal characterization of the human nucleus accumbens.

Dysregulation of the nucleus accumbens (NAc) is implicated in numerous neuropsychiatric disorders. Treatments targeting this area directly (e.g. deep brain stimulation) demonstrate variable efficacy, perhaps owing to non-specific targeting of a functionally heterogeneous nucleus. Here we provide support for this notion, first observing disparate behavioral effects in response to direct simulation of different locations within the NAc in a human patient. These observations motivate a segmentation of the NAc into subregions, which we produce from a diffusion-tractography based analysis of 245 young, unrelated healthy subjects. We further explore the mechanism of these stimulation-induced behavioral responses by identifying the most probable subset of axons activated using a patient-specific computational model. We validate our diffusion-based segmentation using evidence from several modalities, including MRI-based measures of function and microstructure, human post-mortem immunohistochemical staining, and cross-species comparison of cortical-NAc projections that are known to be conserved. Finally, we visualize the passage of individual axon bundles through one NAc subregion in a post-mortem human sample using CLARITY 3D histology corroborated by 7T tractography. Collectively, these findings extensively characterize human NAc subregions and provide insight into their structural and functional distinctions with implications for stereotactic treatments targeting this region.

Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis.

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease-related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders.

Eddy current nulled constrained optimization of isotropic diffusion encoding gradient waveforms.

PURPOSE: Isotropic diffusion encoding efficiently encodes additional microstructural information in combination with conventional linear diffusion encoding. However, the gradient-intensive isotropic diffusion waveforms generate significant eddy currents, which cause image distortions. The purpose of this study is to present a method for designing isotropic diffusion encoding waveforms with intrinsic eddy current nulling. METHODS: Eddy current nulled gradient waveforms were designed using a constrained optimization waveform for a 3T GE Premier MRI system. Encoding waveforms were designed for a variety of eddy current null times and sequence timings to evaluate the achievable b-value. Waveforms were also tested with both eddy current nulling and concomitant field compensation. Distortion reduction was tested in both phantoms and the in vivo human brain. RESULTS: The feasibility of isotropic diffusion encoding with intrinsic correction of eddy current distortion and signal bias from concomitant fields was demonstrated. The constrained optimization algorithm produced gradient waveforms with the specified eddy current null times. The reduction in the achievable diffusion weighting was dependent on the number of eddy current null times. A reduction in the eddy current-induced image distortions was observed in both phantoms and in vivo human subjects. CONCLUSION: The proposed framework allows the design of isotropic diffusion-encoding sequences with reduced image distortion.

Motion-robust reconstruction of multishot diffusion-weighted images without phase estimation through locally low-rank regularization.

PURPOSE: The goal of this work is to propose a motion robust reconstruction method for diffusion-weighted MRI that resolves shot-to-shot phase mismatches without using phase estimation. METHODS: Assuming that shot-to-shot phase variations are slowly varying, spatial-shot matrices can be formed using a local group of pixels to form columns, in which each column is from a different shot (excitation). A convex model with a locally low-rank constraint on the spatial-shot matrices is proposed. In vivo brain and breast experiments were performed to evaluate the performance of the proposed method. RESULTS: The proposed method shows significant benefits when the motion is severe, such as for breast imaging. Furthermore, the resulting images can be used for reliable phase estimation in the context of phase-estimation-based methods to achieve even higher image quality. CONCLUSION: We introduced the shot-locally low-rank method, a reconstruction technique for multishot diffusion-weighted MRI without explicit phase estimation. In addition, its motion robustness can be beneficial to neuroimaging and body imaging.

RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke.

Background and Purpose- Many restorative therapies have been used to study brain repair after stroke. These therapeutic-induced changes have revealed important insights on brain repair and recovery mechanisms; however, the intrinsic changes that occur in spontaneously recovery after stroke is less clear. The goal of this study is to elucidate the intrinsic changes in spontaneous recovery after stroke, by directly investigating the transcriptome of primary motor cortex in mice that naturally recovered after stroke. Methods- Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion. Functional recovery was evaluated using the horizontal rotating beam test. A novel in-depth lesion mapping analysis was used to evaluate infarct size and locations. Ipsilesional and contralesional primary motor cortices (iM1 and cM1) were processed for RNA-sequencing transcriptome analysis. Results- Cluster analysis of the stroke mice behavior performance revealed 2 distinct recovery groups: a spontaneously recovered and a nonrecovered group. Both groups showed similar lesion profile, despite their differential recovery outcome. RNA-sequencing transcriptome analysis revealed distinct biological pathways in the spontaneously recovered stroke mice, in both iM1 and cM1. Correlation analysis revealed that 38 genes in the iM1 were significantly correlated with improved recovery, whereas 74 genes were correlated in the cM1. In particular, ingenuity pathway analysis highlighted the involvement of cAMP signaling in the cM1, with selective reduction of Adora2a (adenosine receptor A2A), Drd2 (dopamine receptor D2), and Pde10a (phosphodiesterase 10A) expression in recovered mice. Interestingly, the expressions of these genes in cM1 were negatively correlated with behavioral recovery. Conclusions- Our RNA-sequencing data revealed a panel of recovery-related genes in the motor cortex of spontaneously recovered stroke mice and highlighted the involvement of contralesional cortex in spontaneous recovery, particularly Adora2a, Drd2, and Pde10a-mediated cAMP signaling pathway. Developing drugs targeting these candidates after stroke may provide beneficial recovery outcome.

Double diffusion encoding MRI for the clinic.

PURPOSE: The purpose of this study is to develop double diffusion encoding (DDE) MRI methods for clinical use. Microscopic diffusion anisotropy measurements from DDE promise greater specificity to changes in tissue microstructure compared with conventional diffusion tensor imaging, but implementation of DDE sequences on whole-body MRI scanners is challenging because of the limited gradient strengths and lengthy acquisition times. METHODS: A custom single-refocused DDE sequence was implemented on a 3T whole-body scanner. The DDE gradient orientation scheme and sequence parameters were optimized based on a Gaussian diffusion assumption. Using an optimized 5-min DDE acquisition, microscopic fractional anisotropy (µFA) maps were acquired for the first time in multiple sclerosis patients. RESULTS: Based on simulations and in vivo human measurements, six parallel and six orthogonal diffusion gradient pairs were found to be the minimum number of diffusion gradient pairs necessary to produce a rotationally invariant measurement of µFA. Simulations showed that optimal precision and accuracy of µFA measurements were obtained using b-values between 1500 and 3000 s/mm2 . The µFA maps showed improved delineation of multiple sclerosis lesions compared with conventional fractional anisotropy and distinct contrast from T2 -weighted fluid attenuated inversion recovery and T1 -weighted imaging. CONCLUSION: The µFA maps can be measured using DDE in a clinical setting and may provide new opportunities for characterizing multiple sclerosis lesions and other types of tissue degeneration. Magn Reson Med 80:507-520, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The separate effects of lipids and proteins on brain MRI contrast revealed through tissue clearing.

Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY. We monitor the temporal dynamics of tissue clearance via NMR spectroscopy, protein assays and optical emission spectroscopy. MRI of cleared brain tissue showed: 1) minimal contrast on standard MRI sequences; 2) increased relaxation times; and 3) diffusion rates close to free water. We conclude that lipids, present in myelin and membranes, are a dominant source of MRI contrast in brain tissue.

Motion correction for functional MRI with three-dimensional hybrid radial-Cartesian EPI.

PURPOSE: Subject motion is a major source of image degradation for functional MRI (fMRI), especially when using multishot sequences like three-dimensional (3D EPI). We present a hybrid radial-Cartesian 3D EPI trajectory enabling motion correction in k-space for functional MRI. METHODS: The EPI "blades" of the 3D hybrid radial-Cartesian EPI sequence, called TURBINE, are rotated about the phase-encoding axis to fill out a cylinder in 3D k-space. Angular blades are acquired over time using a golden-angle rotation increment, allowing reconstruction at flexible temporal resolution. The self-navigating properties of the sequence are used to determine motion parameters from a high temporal-resolution navigator time series. The motion is corrected in k-space as part of the image reconstruction, and evaluated for experiments with both cued and natural motion. RESULTS: We demonstrate that the motion correction works robustly and that we can achieve substantial artifact reduction as well as improvement in temporal signal-to-noise ratio and fMRI activation in the presence of both severe and subtle motion. CONCLUSION: We show the potential for hybrid radial-Cartesian 3D EPI to substantially reduce artifacts for application in fMRI, especially for subject groups with significant head motion. The motion correction approach does not prolong the scan, and no extra hardware is required. Magn Reson Med 78:527-540, 2017. © 2016 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.

Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging.

Purpose To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing-remitting MS and six healthy control subjects underwent diffusion-weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intra-axonal, extra-axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results MS lesions showed increased mean axon diameter (10.3 vs 7.9 µm in the genu, 10.4 vs 9.3 µm in the body, and 10.6 vs 8.2 µm in the splenium; P < .05) and decreased axon density ([0.48 vs 1.1] × 10(10)/m(2) in the genu, [0.40 vs 0.70] × 10(10)/m(2) in the body, and [0.35 vs 1.1] × 10(10)/m(2) in the splenium; P < .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM. (©) RSNA, 2016 Online supplemental material is available for this article.

Accelerating functional MRI using fixed-rank approximations and radial-cartesian sampling.

PURPOSE: Recently, k-t FASTER (fMRI Accelerated in Space-time by means of Truncation of Effective Rank) was introduced for rank-constrained acceleration of fMRI data acquisition. Here we demonstrate improvements achieved through a hybrid three-dimensional radial-Cartesian sampling approach that allows posthoc selection of acceleration factors, as well as incorporation of coil sensitivity encoding in the reconstruction. METHODS: The multicoil rank-constrained reconstruction used hard thresholding and shrinkage on matrix singular values of the space-time data matrix, using sensitivity encoding and the nonuniform Fast Fourier Transform to enforce data consistency in the multicoil non-Cartesian k-t domain. Variable acceleration factors were made possible using a radial increment based on the golden ratio. Both retrospective and prospectively under-sampled data were used to assess the fidelity of the enhancements to the k-t FASTER technique in resting and task-fMRI data. RESULTS: The improved k-t FASTER is capable of tailoring acceleration factors for recovery of different signal components, achieving up to R = 12.5 acceleration in visual-motor task data. The enhancements reduce data matrix reconstruction errors even at much higher acceleration factors when compared directly with the original k-t FASTER approach. CONCLUSION: We have shown that k-t FASTER can be used to significantly accelerate fMRI data acquisition with little penalty to data quality. Magn Reson Med 76:1825-1836, 2016. © 2016 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.

Q-space truncation and sampling in diffusion spectrum imaging.

PURPOSE: To characterize the q-space truncation and sampling on the spin-displacement probability density function (PDF) in diffusion spectrum imaging (DSI). METHODS: DSI data were acquired using the MGH-USC connectome scanner (Gmax = 300 mT/m) with bmax = 30,000 s/mm2 , 17 × 17 × 17, 15 × 15 × 15 and 11 × 11 × 11 grids in ex vivo human brains and bmax = 10,000 s/mm2 , 11 × 11 × 11 grid in vivo. An additional in vivo scan using bmax =7,000 s/mm2 , 11 × 11 × 11 grid was performed with a derated gradient strength of 40 mT/m. PDFs and orientation distribution functions (ODFs) were reconstructed with different q-space filtering and PDF integration lengths, and from down-sampled data by factors of two and three. RESULTS: Both ex vivo and in vivo data showed Gibbs ringing in PDFs, which becomes the main source of artifact in the subsequently reconstructed ODFs. For down-sampled data, PDFs interfere with the first replicas or their ringing, leading to obscured orientations in ODFs. CONCLUSION: The minimum required q-space sampling density corresponds to a field-of-view approximately equal to twice the mean displacement distance (MDD) of the tissue. The 11 × 11 × 11 grid is suitable for both ex vivo and in vivo DSI experiments. To minimize the effects of Gibbs ringing, ODFs should be reconstructed from unfiltered q-space data with the integration length over the PDF constrained to around the MDD. Magn Reson Med 76:1750-1763, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

The impact of gradient strength on in vivo diffusion MRI estimates of axon diameter.

Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3T human MRI scanner with a maximum gradient strength of 300 mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293 mT/m and diffusion times encompassing short (16 and 25 ms) and long (60 and 94 ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners.