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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.

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.

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 novel 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.

Depression affects more than 16 million American adults and more than half do not respond to medication. Transcranial magnetic stimulation (TMS) is an important anti-depressant treatment that targets specific brain circuits responsible for mood and behavior. TMS efficacy and risk is strongly linked to correct TMS coil placement and can be significantly improved by accurate neuronavigation. In this paper, we present tools for the development of a novel mixed reality neuronavigation setup that allows the TMS operator to view the patient's brain anatomy directly overlaid on the head. This is performed by integrating patient tracking and visualization of brain magnetic resonance imaging (MRI) to provide a streamlined visualization of the patient's anatomy in a single immersive environment.

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole–mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

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 ± 0.09 μm) than in the genu (5.55 ± 0.15 μm) and splenium (5.4 ± 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.

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.

We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.

Background: TMS activations of white matter depend not only on the distance from the coil, but also on the orientation of the axons relative to the TMS-induced electric field, and especially on axonal bends that create strong local field gradient maxima. Therefore, tractography contains potentially useful information for TMS targeting. Objective/methods: Here, we utilized 1-mm resolution diffusion and structural T1-weighted MRI to construct large-scale tractography models, and localized TMS white matter activations in motor cortex using electromagnetic forward modeling in a boundary element model (BEM). Results: As expected, in sulcal walls, pyramidal cell axonal bends created preferred sites of activation that were not found in gyral crowns. The model agreed with the well-known coil orientation sensitivity of motor cortex, and also suggested unexpected activation distributions emerging from the E-field and tract configurations. We further propose a novel method for computing the optimal coil location and orientation to maximally stimulate a pre-determined axonal bundle. Conclusions: Diffusion MRI tractography with electromagnetic modeling may improve spatial specificity and efficacy of TMS.

The macaque monkey is an important model for cognitive and sensory neuroscience that has been used extensively in behavioral, electrophysiological, molecular and, more recently, neuroimaging studies. However, macaque MRI has unique technical differences relative to human MRI, such as the geometry of highly parallel receive arrays, which must be addressed to optimize imaging performance. A 22-channel receive coil array was constructed specifically for rapid high-resolution anesthetized macaque monkey MRI at 3 T. A local Helmholtz transmit coil was used for excitation. Signal-to-noise ratios (SNRs) and noise amplification for parallel imaging were compared with those of single- and four-channel receive coils routinely used for macaque MRI. The 22-channel coil yielded significant improvements in SNR throughout the brain. Using this coil, the SNR in peripheral brain was 2.4 and 1.7 times greater than that obtained with single- or four-channel coils, respectively. In the central brain, the SNR gain was 1.5 times that of both the single- and four-channel coils. Finally, the performance of the array for functional, anatomical and diffusion-weighted imaging was evaluated. For all three modalities, the use of the 22-channel array allowed for high-resolution and accelerated image acquisition.

Diffusion-weighted steady-state free precession (DW-SSFP) accumulates signal from multiple echoes over several TRs yielding a strong sensitivity to diffusion with short gradient durations and imaging times. Although the DW-SSFP signal is well characterized for isotropic, Gaussian diffusion, it is unclear how the DW-SSFP signal propagates in inhomogeneous media such as brain tissue. This article presents a more general analytical expression for the DW-SSFP signal which accommodates Gaussian and non-Gaussian spin displacement probability density functions. This new framework for calculating the DW-SSFP signal is used to investigate signal behavior for a single fiber, crossing fibers, and reflective barriers. DW-SSFP measurements in the corpus callosum of a fixed brain are shown to be in good agreement with theoretical predictions. Further measurements in fixed brain tissue also demonstrate that 3D DW-SSFP out-performs 3D diffusion weighted spin echo in both SNR and CNR efficiency providing a compelling example of its potential to be used for high resolution diffusion tensor imaging. Magn Reson Med 60:405–413, 2008. © 2008 Wiley-Liss, Inc.

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies.

In this study, the authors performed deep brain stimulation (DBS) of the subgenual anterior cingulate cortex (SACC) in a patient with a history of bipolar disorder. After a right thalamic stroke, intractable depression without mood elevation or a mixed state developed in this patient. He underwent bilateral SACC DBS and died 16 months afterwards. Anatomical connections were studied in this patient preoperatively and postmortem using diffusion tractography (DT). A comparison of in vivo and high resolution ex vivo connectivity patterns was performed as a measure of the utility of in vivo DT in presurgical planning for DBS. Diagnostic measures included neuropsychological testing, preoperative and ex vivo DT, and macroscopic neuropathological assessment. Post-DBS depression rating scores did not improve. In vivo and ex vivo DT revealed markedly reduced limbic projections from the thalamus and SACC to the amygdala in the right (stroke-affected) hemisphere. A highly selective right mediothalamic lesion was associated with the onset of refractory depression. Reduced amygdalar-thalamic and amygdalar-SACC connections could be a contraindication to DBS for depression. Correspondence between preoperative and higher resolution ex vivo DT supports the validity of DT as a presurgical planning tool for DBS.

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.

Size-optimized 32-channel receive array coils were developed for five age groups, neonates, 6 months old, 1 year old, 4 years old, and 7 years old, and evaluated for pediatric brain imaging. The array consisted of overlapping circular surface coils laid out on a close-fitting coil-former. The two-section coil former design was obtained from surface contours of aligned three-dimensional MRI scans of each age group. Signal-to-noise ratio and noise amplification for parallel imaging were evaluated and compared to two coils routinely used for pediatric brain imaging; a commercially available 32-channel adult head coil and a pediatric-sized birdcage coil. Phantom measurements using the neonate, 6-month-old, 1-year-old, 4-year-old, and 7-year-old coils showed signal-to-noise ratio increases at all locations within the brain over the comparison coils. Within the brain cortex the five dedicated pediatric arrays increased signal-to-noise ratio by up to 3.6-, 3.0-, 2.6-, 2.3-, and 1.7-fold, respectively, compared to the 32-channel adult coil, as well as improved G-factor maps for accelerated imaging. This study suggests that a size-tailored approach can provide significant sensitivity gains for accelerated and unaccelerated pediatric brain imaging.

AIM: To compare the structural and functional differences in the brains of children who practise judo against controls using diffusion tensor imaging (DTI).MATERIALS AND METHODS: This prospective study was approved by the Institutional Review Board. Young judo athletes (n = 14; 17-21 years; mean, 19 years) and age-matched healthy controls (n = 7; 16-21 years; mean, 19 years) underwent standard structural brain magnetic resonance imaging (MRI) and DTI using a 3 T MRI system. Brain MRI images were reviewed for evidence of injury or structural anomalies. Tractography and the fractional anisotropy (FA) of white matter tracts were calculated. Between groups comparison was conducted using two-sample t-test.RESULTS: The brains of the young judo athletes were structurally normal. Significantly increased FA, up to 18% in the internal capsule (p

Steady-state diffusion-weighted imaging (DWI) has long been recognized to offer potential benefits over conventional spin-echo methods. This family of pulse sequences is highly efficient and compatible with three-dimensional acquisitions, which could enable high-resolution, low-distortion images. However, the same properties that lead to its efficiency make steady-state imaging highly susceptible to motion and create a complicated signal with dependence on T(1), T(2) and flip angle. Recent developments in gradient hardware, motion-mitigation techniques and signal analysis offer potential solutions to these problems, reviving interest in steady-state DWI. This review offers a description of steady-state DWI signal formation and provides an overview of the current methods for steady-state DWI acquisition and analysis.

While most diffusion-weighted imaging (DWI) is acquired using single-shot diffusion-weighted spin-echo echo-planar imaging, steady-state DWI is an alternative method with the potential to achieve higher-resolution images with less distortion. Steady-state DWI is, however, best suited to a segmented three-dimensional acquisition and thus requires three-dimensional navigation to fully correct for motion artifacts. In this paper, a method for three-dimensional motion-corrected steady-state DWI is presented. The method uses a unique acquisition and reconstruction scheme named trajectory using radially batched internal navigator echoes (TURBINE). Steady-state DWI with TURBINE uses slab-selection and a short echo-planar imaging (EPI) readout each pulse repetition time. Successive EPI readouts are rotated about the phase-encode axis. For image reconstruction, batches of cardiac-synchronized readouts are used to form three-dimensional navigators from a fully sampled central k-space cylinder. In vivo steady-state DWI with TURBINE is demonstrated in human brain. Motion artifacts are corrected using refocusing reconstruction and TURBINE images prove less distorted compared to two-dimensional single-shot diffusion-weighted-spin-EPI

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.

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.

Perhaps more than any other "-omics" endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depend on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an "image" of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain's structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with G(max) = 300 mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to achieve a DSI scan in less than 5 min. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coil at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing.

Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in gray matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical gray matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1 mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1.

Diffusion imaging of post-mortem brains could provide valuable data for validation of diffusion tractography of white matter pathways. Long scans (e.g., overnight) may also enable high-resolution diffusion images for visualization of fine structures. However, alterations to post-mortem tissue (T2 and diffusion coefficient) present significant challenges to diffusion imaging with conventional diffusion-weighted spin echo (DW-SE) acquisitions, particularly for imaging human brains on clinical scanners. Diffusion-weighted steady-state free precession (DW-SSFP) has been proposed as an alternative acquisition technique to ameliorate this tradeoff in large-bore clinical scanners. In this study, both DWSE and DW-SSFP are optimized for use in fixed white matter on a clinical 3-Tesla scanner. Signal calculations predict superior performance from DW-SSFP across a broad range of protocols and conditions. DW-SE and DW-SSFP data in a whole, post-mortem human brain are compared for 6- and 12-hour scan durations. Tractography is performed in major projection, commissural and association tracts (corticospinal tract, corpus callosum, superior longitudinal fasciculus and cingulum bundle). The results demonstrate superior tract-tracing from DW-SSFP data, with 6-hour DW-SSFP data performing as well as or better than 12-hour DW-SE scans. These results suggest that DW-SSFP may be a preferred method for diffusion imaging of post-mortem human brains. The ability to estimate multiple fibers in imaging voxels is also demonstrated, again with greater success in DW-SSFP data., Highlights ► Comparison of DW-SE and DW-SSFP for post-mortem imaging on clinical scanners. ► Optimization of protocols predicts 50-130% higher SNR efficiency in DW-SSFP. ► Comparison of tractography 6- and 12-hour DW-SE and DW-SSFP scans. ► Lower uncertainty on fibre direction in DW-SSFP produces superior tractography. ► Crossing fibres can be estimated from 12-hour DW-SSFP data.

Size-optimized 32-channel receive array coils were developed for five age groups, neonates, 6 months old, 1 year old, 4 years old, and 7 years old, and evaluated for pediatric brain imaging. The array consisted of overlapping circular surface coils laid out on a close-fitting coil-former. The two-section coil former design was obtained from surface contours of aligned three-dimensional MRI scans of each age group. Signal-to-noise ratio and noise amplification for parallel imaging were evaluated and compared to two coils routinely used for pediatric brain imaging; a commercially available 32-channel adult head coil and a pediatric-sized birdcage coil. Phantom measurements using the neonate, 6-month-old, 1-year-old, 4-year-old, and 7-year-old coils showed signal-to-noise ratio increases at all locations within the brain over the comparison coils. Within the brain cortex the five dedicated pediatric arrays increased signal-to-noise ratio by up to 3.6-, 3.0-, 2.6-, 2.3-, and 1.7-fold, respectively, compared to the 32-channel adult coil, as well as improved G-factor maps for accelerated imaging. This study suggests that a size-tailored approach can provide significant sensitivity gains for accelerated and unaccelerated pediatric brain imaging.

While most diffusion-weighted imaging (DWI) is acquired using single-shot diffusion-weighted spin-echo echo-planar imaging, steady-state DWI is an alternative method with the potential to achieve higher-resolution images with less distortion. Steady-state DWI is, however, best suited to a segmented three-dimensional acquisition and thus requires three-dimensional navigation to fully correct for motion artifacts. In this paper, a method for three-dimensional motion-corrected steady-state DWI is presented. The method uses a unique acquisition and reconstruction scheme named trajectory using radially batched internal navigator echoes (TURBINE). Steady-state DWI with TURBINE uses slab-selection and a short echo-planar imaging (EPI) readout each pulse repetition time. Successive EPI readouts are rotated about the phase-encode axis. For image reconstruction, batches of cardiac-synchronized readouts are used to form three-dimensional navigators from a fully sampled central k-space cylinder. In vivo steady-state DWI with TURBINE is demonstrated in human brain. Motion artifacts are corrected using refocusing reconstruction and TURBINE images prove less distorted compared to two-dimensional single-shot diffusion-weighted-spin-EPI.

High resolution diffusion tensor imaging and tractography of ex vivo brain specimens has the potential to reveal detailed fibre architecture not visible on in vivo images. Previous ex vivo diffusion imaging experiments have focused on animal brains or small sections of human tissue since the unfavourable properties of fixed tissue (including short T(2) and low diffusion rates) demand the use of very powerful gradient coils that are too small to accommodate a whole, human brain. This study proposes the use of diffusion-weighted steady-state free precession (DW-SSFP) as a method of extending the benefits of ex vivo DTI and tractography to whole, human, fixed brains on a clinical 3 T scanner. DW-SSFP is a highly efficient pulse sequence; however, its complicated signal dependence precludes the use of standard diffusion tensor analysis and tractography. In this study, a method is presented for modelling anisotropy in the context of DW-SSFP. Markov Chain Monte Carlo sampling is used to estimate the posterior distributions of model parameters and it is shown that it is possible to estimate a tight distribution on the principal axis of diffusion at each voxel using DW-SSFP. Voxel-wise estimates are used to perform tractography in a whole, fixed human brain. A direct comparison between 3D diffusion-weighted spin echo EPI and 3D DW-SSFP-EPI reveals that the orientation of the principal diffusion axis can be inferred on with a higher degree of certainty using a 3D DW-SSFP-EPI even with a 68% shorter acquisition time.

The anatomical connections of the pedunculopontine nucleus (PPN), a brainstem structure associated with locomotion, have been determined recently in healthy humans using probabilistic diffusion tractography (PDT). In order to compare these with histologically demonstrated connections of the PPN in monkeys, and thus to support the use of PDT in humans, we have carried out PDT in a fixed rhesus monkey ( Macaca mulatta ) brain. Probabilistic diffusion tractography was carried out in a fixed post-mortem rhesus monkey brain using diffusion data acquired at 3T MRI (60 directions × 5 averages, b = 3000 s/mm 2 , matrix size = 104 × 132 × 96, 720 × 720 × 720 μm voxels). We identified the major connections of the PPN from single seed voxels that could be confidently located within the nucleus on the diffusion images. The organisation of these connections within a 3 × 3 × 3 voxel (∼10 mm 3 ) region surrounding the initial seed voxel was then examined. PDT confirmed that the rhesus monkey PPN connections with the basal ganglia and motor cortical areas matched those previously demonstrated using conventional anatomical tracing techniques. Furthermore, although the organisation of subcortical connections within the PPN has not been extensively demonstrated in animals, we show here in a rhesus monkey that there are clearly separated connections of the PPN with the thalamus, substantia nigra, and subthalamic nucleus. Thus, in addition to increasing confidence in the accuracy of PDT for tracing PPN connections and determining the organisation of these connections within the PPN in vivo , our observations suggest that diffusion tractography will be a useful new technique to rapidly identify connections in animal brains pre-mortem and post-mortem.

A novel short echo-time 1 H chemical shift imaging (CSI) pulse sequence is presented that incorporates localization by adiabatic selective refocusing (LASER) for FOV-reduction, k-space weighted averaging and macromolecule subtraction, to obtain quantitative concentration measurements of N-acetyl-aspartate, glutamate, glucose, myo-inositol, creatine and choline using a nominal voxel size of 0.56cm 3 . A comparison of spectral quality and metabolite concentration measurements was made between LASER-CSI and LASER-single voxel spectroscopy (SVS) in a region of homogeneous parietal white matter (N ¼8). No significant differences were found in linewidths, signal-to-noise ratios or the effectiveness of the macromolecule subtraction between SVS and CSI. Water suppression was 45% more effective in SVS than in CSI (p

Objectives: To investigate changes in tumour tissue oxygenation throughout the tumour growth–regression–relapse cycle in an androgen-dependent animal tumour model. Materials and methods: 19F T1 relaxometry of Perfluoro-15-Crown-5-Ether was used to measure in vivo partial oxygen pressure (pO2) of Shionogi tumours on a 2.35-T MR scanner. Perfluoro-15-Crown-5-Ether was administered as an emulsion injected intravenously or as a neat compound injected directly into the tumour. Non-localized, tumour 19F T1 measurements, made at multiple time points throughout the tumour cycle, were translated into pO2 levels. Results: No correlation between tumour size and pO2 values was found. Values of pO2 for growing tumours (50 ± 30 torr) were significantly lower than for regressing and relapsing tumours after 9 days post-castration (70 ± 10 torr, p

Multiple sclerosis (MS) is a chronic inflammatory neurological condition characterised by both focal and diffuse neurodegeneration and demyelination throughout the central nervous system. However, associations between these individual pathological processes remain poorly defined. Here we present a highly novel combination of whole brain post-mortem diffusion and structural MRI with quantitative histology to assess patterns of MS pathology. Two white matter tracts and their associated grey matter structures were assessed in nine fixed whole brains on the basis of their documented involvement in MS: that running from lateral geniculate nucleus to primary visual cortex, and from mediodorsal nucleus of the thalamus to prefrontal cortex. Cortical thickness was correlated significantly with both tract myelination and thalamic nucleus cell density within the anatomically distinct tract structures. Such correlations were not observed between these markers of neurodegeneration across the two tract types. In addition, diffusion MRI metrics in all tracts were correlated significantly with histologically defined levels of tract myelination. These data demonstrate for the first time the potential relevance of functional anatomical connectivity to the spread of MS pathology in a “tract-specific” pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted MRI and tissue microstructure in fixed samples validates the exciting potential of this imaging modality for future neuropathological studies.