Depth- and curvature-based quantitative susceptibility mapping analyses of cortical iron in Alzheimer's disease.

In addition to amyloid beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been associated with elevated iron in deep gray matter nuclei using quantitative susceptibility mapping (QSM). However, only a few studies have examined cortical iron, using more macroscopic approaches that cannot assess layer-specific differences. Here, we conducted column-based QSM analyses to assess whether AD-related increases in cortical iron vary in relation to layer-specific differences in the type and density of neurons. We obtained global and regional measures of positive (iron) and negative (myelin, protein aggregation) susceptibility from 22 adults with AD and 22 demographically matched healthy controls. Depth-wise analyses indicated that global susceptibility increased from the pial surface to the gray/white matter boundary, with a larger slope for positive susceptibility in the left hemisphere for adults with AD than controls. Curvature-based analyses indicated larger global susceptibility for adults with AD versus controls; the right hemisphere versus left; and gyri versus sulci. Region-of-interest analyses identified similar depth- and curvature-specific group differences, especially for temporo-parietal regions. Finding that iron accumulates in a topographically heterogenous manner across the cortical mantle may help explain the profound cognitive deterioration that differentiates AD from the slowing of general motor processes in healthy aging.

Flexible multi-purpose integrated RF/shim coil array for MRI and localized B0 shimming.

PURPOSE: To develop a flexible, lightweight, and multi-purpose integrated parallel reception, excitation, and shimming (iPRES) coil array that can conform to the subject's anatomy and perform MR imaging and localized B0 shimming in different anatomical regions with a high SNR, shimming performance, ease of positioning, and subject comfort. METHODS: A four-channel flexible iPRES coil array was constructed by enabling RF and direct currents to flow on the same flexible coil elements for imaging and shimming, respectively. Shimming experiments were performed with the coil array wrapped around the knee or neck of healthy subjects to demonstrate its high shimming performance and versatility. Additionally, its SNR and shimming performance in the knee were compared to those obtained with the coil array wrapped around a larger rigid tube designed to fit most knee sizes. RESULTS: Shimming with the coil array wrapped around the knee or neck resulted in an average reduction in B0 RMSE of 50.1% and 40.5% relative to first-order and second-order spherical harmonic shimming, respectively, and substantially reduced distortions in DWI images. In contrast, shimming the knee with the coil array wrapped around the rigid tube only provided a 29.6% reduction in B0 RMSE, whereas the SNR was reduced by 58.7%. CONCLUSION: The flexible iPRES coil array can conform to different anatomical regions and perform imaging and localized B0 shimming with a higher SNR, shimming performance, ease of positioning, and comfort compared to a rigid iPRES coil array, which should be valuable for many applications throughout the human body.

High-resolution multi-shot diffusion imaging of structural networks in healthy neurocognitive aging.

Healthy neurocognitive aging has been associated with the microstructural degradation of white matter pathways that connect distributed gray matter regions, assessed by diffusion-weighted imaging (DWI). However, the relatively low spatial resolution of standard DWI has limited the examination of age-related differences in the properties of smaller, tightly curved white matter fibers, as well as the relatively more complex microstructure of gray matter. Here, we capitalize on high-resolution multi-shot DWI, which allows spatial resolutions < 1 mm3 to be achieved on clinical 3T MRI scanners. We assessed whether traditional diffusion tensor-based measures of gray matter microstructure and graph theoretical measures of white matter structural connectivity assessed by standard (1.5 mm3 voxels, 3.375 µl volume) and high-resolution (1 mm3 voxels, 1µl volume) DWI were differentially related to age and cognitive performance in 61 healthy adults 18-78 years of age. Cognitive performance was assessed using an extensive battery comprising 12 separate tests of fluid (speed-dependent) cognition. Results indicated that the high-resolution data had larger correlations between age and gray matter mean diffusivity, but smaller correlations between age and structural connectivity. Moreover, parallel mediation models including both standard and high-resolution measures revealed that only the high-resolution measures mediated age-related differences in fluid cognition. These results lay the groundwork for future studies planning to apply high-resolution DWI methodology to further assess the mechanisms of both healthy aging and cognitive impairment.

Numerical simulations of an integrated radio-frequency/wireless coil design for simultaneous acquisition and wireless transfer of magnetic resonance imaging data.

Objective.A novel magnetic resonance imaging (MRI) radio-frequency (RF) coil design, termed an integrated RF/wireless (iRFW) coil design, can simultaneously perform MRI signal reception and far-field wireless data transfer with the same coil conductors between the coil in the scanner bore and an access point (AP) on the scanner room wall. The objective of this work is to optimize the design inside the scanner bore to provide a link budget between the coil and the AP for the wireless transmission of MRI data.Approach.Electromagnetic simulations were performed at the Larmor frequency of a 3T scanner and in a WiFi wireless communication band to optimize the radius and position of an iRFW coil located near the head of a human model inside the scanner bore, which were validated by performing both imaging and wireless experiments.Main Results.The simulated iRFW coil with a 40 mm radius positioned near the model forehead provided: a signal-to-noise ratio (SNR) comparable to that of a traditional RF coil with the same radius and position, a power absorbed by the human model within regulatory limits, and a gain pattern in the scanner bore resulting in a link budget of 51.1 dB between the coil and an AP located behind the scanner 3 m from the isocenter, which would be sufficient to wirelessly transfer MRI data acquired with a 16-channel coil array. The SNR, gain pattern, and link budget for initial simulations were validated by experimental measurements in an MRI scanner and anechoic chamber to provide confidence in this methodology. These results show that the iRFW coil design must be optimized within the scanner bore for the wireless transfer of MRI data.Significance.The MRI RF coil array coaxial cable assembly connected to the scanner increases patient setup time, can present a serious burn risk to patients and is an obstacle to the development of the next generation of lightweight, flexible or wearable coil arrays that provide an improved coil sensitivity for imaging. Significantly, the RF coaxial cables and corresponding receive chain electronics can be removed from within the scanner by integrating the iRFW coil design into an array for the wireless transmission of MRI data outside of the bore.

Column-based cortical depth analysis of the diffusion anisotropy and radiality in submillimeter whole-brain diffusion tensor imaging of the human cortical gray matter in vivo.

High-resolution diffusion tensor imaging (DTI) can noninvasively probe the microstructure of cortical gray matter in vivo. In this study, 0.9-mm isotropic whole-brain DTI data were acquired in healthy subjects with an efficient multi-band multi-shot echo-planar imaging sequence. A column-based analysis that samples the fractional anisotropy (FA) and radiality index (RI) along radially oriented cortical columns was then performed to quantitatively analyze the FA and RI dependence on the cortical depth, cortical region, cortical curvature, and cortical thickness across the whole brain, which has not been simultaneously and systematically investigated in previous studies. The results showed characteristic FA and RI vs. cortical depth profiles, with an FA local maximum and minimum (or two inflection points) and a single RI maximum at intermediate cortical depths in most cortical regions, except for the postcentral gyrus where no FA peaks and a lower RI were observed. These results were consistent between repeated scans from the same subjects and across different subjects. They were also dependent on the cortical curvature and cortical thickness in that the characteristic FA and RI peaks were more pronounced i) at the banks than at the crown of gyri or at the fundus of sulci and ii) as the cortical thickness increases. This methodology can help characterize variations in microstructure along the cortical depth and across the whole brain in vivo, potentially providing quantitative biomarkers for neurological disorders.

An iPRES-W Coil Array for Simultaneous Imaging and Wireless Localized B0 Shimming of the Cervical Spinal Cord.

PURPOSE: To develop a wireless integrated parallel reception, excitation, and shimming (iPRES-W) coil array for simultaneous imaging and wireless localized B0 shimming, and to demonstrate its ability to correct for distortions in DTI of the spinal cord in vivo. METHODS: A 4-channel coil array was modified to allow an RF current at the Larmor frequency and a direct current to flow on each coil element, enabling imaging and localized B0 shimming, respectively. One coil element was further modified to allow additional RF currents within a wireless communication band to flow on it to wirelessly control the direct currents for shimming, which were supplied from a battery pack within the scanner bore. The RF signals for imaging were transferred via conventional wired connections. Experiments were conducted to evaluate the RF, B0 shimming, and wireless performance of this coil design. RESULTS: The coil modifications did not degrade the SNR. Wireless localized B0 shimming with the iPRES-W coil array substantially reduced the B0 RMSE (-57.5% on average) and DTI distortions in the spinal cord. The antenna radiation efficiency, antenna gain pattern, and battery power consumption of an iPRES-W coil measured in an anechoic chamber were minimally impacted by the introduction of a saline phantom representing tissue. CONCLUSION: The iPRES-W coil array can perform imaging and wireless localized B0 shimming of the spinal cord with no SNR degradation, with minimal change in wireless performance and without any scanner modifications or additional antenna systems within the scanner bore.

Strengthened and posterior-shifted structural rich-club organization in people who use cocaine.

BACKGROUND: People with cocaine use disorder (CUD) often have abnormal cognitive function and brain structure. Cognition is supported by brain networks that typically have characteristics like rich-club organization, which is a group of regions that are highly connected across the brain and to each other, and small worldness, which is a balance between local and long-distance connections. However, it is unknown whether there are abnormalities in structural brain network connectivity of CUD. METHODS: Using diffusion-weighted imaging, we measured structural connectivity in 37 people with CUD and 38 age-matched controls. We identified differences in rich-club organization and whether such differences related to small worldness and behavior. We also tested whether rich-club reorganization was associated with caudate and putamen structural connectivity due to the relevance of the dopamine system to cocaine use. RESULTS: People with CUD had a higher normalized rich-club coefficient than controls, more edges connecting rich-club nodes to each other and to non-rich-club nodes, and fewer edges connecting non-rich-club nodes. Rich-club nodes were shifted posterior and lateral. Rich-club reorganization was related to lower clustered connectivity around individual nodes found in CUD, to increased impulsivity, and to a decrease in caudate connectivity. CONCLUSIONS: These findings are consistent with previous work showing increased rich-club connectivity in conditions associated with a hypofunctional dopamine system. The posterior shift in rich-club nodes in CUD suggests that the structural connectivity of posterior regions may be more impacted than previously recognized in models based on brain function and morphology.

Cortical iron mediates age-related decline in fluid cognition.

Brain iron dyshomeostasis disrupts various critical cellular functions, and age-related iron accumulation may contribute to deficient neurotransmission and cell death. While recent studies have linked excessive brain iron to cognitive function in the context of neurodegenerative disease, little is known regarding the role of brain iron accumulation in cognitive aging in healthy adults. Further, previous studies have focused primarily on deep gray matter regions, where the level of iron deposition is highest. However, recent evidence suggests that cortical iron may also contribute to cognitive deficit and neurodegenerative disease. Here, we used quantitative susceptibility mapping (QSM) to measure brain iron in 67 healthy participants 18-78 years of age. Speed-dependent (fluid) cognition was assessed from a battery of 12 psychometric and computer-based tests. From voxelwise QSM analyses, we found that QSM susceptibility values were negatively associated with fluid cognition in the right inferior temporal gyrus, bilateral putamen, posterior cingulate gyrus, motor, and premotor cortices. Mediation analysis indicated that susceptibility in the right inferior temporal gyrus was a significant mediator of the relation between age and fluid cognition, and similar effects were evident for the left inferior temporal gyrus at a lower statistical threshold. Additionally, age and right inferior temporal gyrus susceptibility interacted to predict fluid cognition, such that brain iron was negatively associated with a cognitive decline for adults over 45 years of age. These findings suggest that iron may have a mediating role in cognitive decline and may be an early biomarker of neurodegenerative disease.

Recent Advances in Radio-Frequency Coil Technologies: Flexible, Wireless, and Integrated Coil Arrays.

Radio-frequency (RF) coils are to magnetic resonance imaging (MRI) scanners what eyes are to the human body. Because of their critical importance, there have been constant innovations driving the rapid development of RF coil technologies. Over the past four decades, the breadth and depth of the RF coil technology evolution have far exceeded the space allowed for this review article. However, these past developments have laid the very foundation on which some of the recent technical breakthroughs are built upon. Here, we narrow our focus on some of the most recent RF coil advances, specifically, on flexible, wireless, and integrated coil arrays. To provide a detailed review, we discuss the theoretical underpinnings, experimental implementations, promising results, as well as future outlooks covering these exciting topics. These recent innovations have greatly improved patient comfort and ease of scan, while also increasing the signal-to-noise ratio, image resolution, temporal throughput, and diagnostic and treatment accuracy. Together with advances in other MRI subfields, they will undoubtedly continue to drive the field forward and lead us to an ever more exciting future. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

Application of an integrated radio-frequency/shim coil technology for signal recovery in fMRI.

PURPOSE: Gradient-echo echo-planar imaging (EPI), which is typically used for blood oxygenation level-dependent (BOLD) functional MRI (fMRI), suffers from distortions and signal loss caused by localized B0 inhomogeneities. Such artifacts cannot be effectively corrected for with the low-order spherical harmonic (SH) shim coils available on most scanners. The integrated parallel reception, excitation, and shimming (iPRES) coil technology allows radiofrequency (RF) and direct currents to flow on each coil element, enabling imaging and localized B0 shimming with one coil array. iPRES was previously used to correct for distortions in spin-echo EPI and is further developed here to also recover signal loss in gradient-echo EPI. METHODS: The cost function in the shim optimization, which typically uses a single term representing the B0 inhomogeneity, was modified to include a second term representing the signal loss, with an adjustable weight to optimize the trade-off between distortion correction and signal recovery. Simulations and experiments were performed to investigate the shimming performance. RESULTS: Slice-optimized shimming with iPRES and the proposed cost function substantially reduced the signal loss in the inferior frontal and temporal brain regions compared to shimming with iPRES and the original cost function or 2nd -order SH shimming with either cost function. In breath-holding fMRI experiments, the ΔB0 and signal loss root-mean-square errors decreased by -34.3% and -56.2%, whereas the EPI signal intensity and number of activated voxels increased by 60.3% and 174.0% in the inferior frontal brain region. CONCLUSION: iPRES can recover signal loss in gradient-echo EPI, which is expected to improve BOLD fMRI studies in brain regions suffering from signal loss.

DTI Tract-Based Quantitative Susceptibility Mapping: An Initial Feasibility Study to Investigate the Potential Role of Myelination in Brain Connectivity Change in Cerebral Palsy Patients During Autologous Cord Blood Cell Therapy Using a Rotationally-Invariant Quantitative Measure.

BACKGROUND: Previous studies using diffusion tensor imaging (DTI)-based connectome analysis revealed improved connectivity in cerebral palsy (CP) patients who underwent autologous umbilical cord blood (UCB) stem-cell therapy. However, the potential mechanism for the connectivity increase remains unclear and needs to be further elucidated. PURPOSE: To develop a technique with improved accuracy for quantitative susceptibility mapping (QSM) with unique sensitivity to myelin, and demonstrate its use in elucidating the underlying mechanism of the observed motor function improvement and brain connectivity increase in CP patients who received autologous UCB stem-cell therapy. STUDY TYPE: Prospective. POPULATION: A cohort of eight pediatric CP patients (2.6 ± 0.6 years of age) with intact corticospinal tracts (CST) from a randomized, placebo-controlled trial of autologous UCB stem-cell therapy in CP children was included in this study. FIELD STRENGTH/SEQUENCE: DTI and 3D spoiled gradient recalled (SPGR) QSM at 3.0T. ASSESSMENT: Pre- and posttreatment magnetic susceptibility (χ) and the rotationally-invariant magnetic susceptibility anisotropy (MSA) along the CST were derived. Behavioral changes were assessed using the 66-item Gross Motor Function Measurement. Changes in χ and MSA were compared between patients with and without substantial behavioral improvements. STATISTICAL TESTS: Two-sample t-tests were performed to assess the differences in the changes of measurements of interest (Δχ, ΔMSA, and ΔFA) between patients who significantly improved and those who did not. RESULTS: Patients who demonstrated posttreatment motor improvements exceeding expectations showed significantly more diamagnetic Δχ in the periventricular region along the CST (P = 0.003). Further analysis on the ΔMSA of this region was significantly increased (P = 0.006) for high responders, along with concurrent FA increase. DATA CONCLUSION: These initial findings suggest that the DTI tract-based QSM method has the potential to characterize white matter changes associated with behavioral improvements in CP children who underwent cord blood stem-cell therapy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Toward direct MRI of neuro-electro-magnetic oscillations in the human brain.

PURPOSE: Neuroimaging techniques are widely used to investigate the function of the human brain, but none are currently able to accurately localize neuronal activity with both high spatial and temporal specificity. Here, a new in vivo MRI acquisition and analysis technique based on the spin-lock mechanism is developed to noninvasively image local magnetic field oscillations resulting from neuroelectric activity in specifiable frequency bands. METHODS: Simulations, phantom experiments, and in vivo experiments using an eyes-open/eyes-closed task in 8 healthy volunteers were performed to demonstrate its sensitivity and specificity for detecting oscillatory neuroelectric activity in the alpha-band (8-12 Hz). A comprehensive postprocessing procedure was designed to enhance the neuroelectric signal, while minimizing any residual hemodynamic and physiological confounds. RESULTS: The phantom results show that this technique can detect 0.06-nT magnetic field oscillations, while the in vivo results demonstrate that it can image task-based modulations of neuroelectric oscillatory activity in the alpha-band. Multiple control experiments and a comparison with conventional BOLD functional MRI suggest that the activation was likely not due to any residual hemodynamic or physiological confounds. CONCLUSION: These initial results provide evidence suggesting that this new technique has the potential to noninvasively and directly image neuroelectric activity in the human brain in vivo. With further development, this approach offers the promise of being able to do so with a combination of spatial and temporal specificity that is beyond what can be achieved with existing neuroimaging methods, which can advance our ability to study the functions and dysfunctions of the human brain.

Integrated radio-frequency/wireless coil design for simultaneous MR image acquisition and wireless communication.

PURPOSE: An innovative radio-frequency (RF) coil design that allows RF currents both at the Larmor frequency and in a wireless communication band to flow on the same coil is proposed to enable simultaneous MRI signal reception and wireless data transfer, thereby minimizing the number of wired connections in the scanner without requiring any modifications or additional hardware within the scanner bore. METHODS: As a first application, the proposed integrated RF/wireless coil design was further combined with an integrated RF/shim coil design to perform not only MR image acquisition and wireless data transfer, but also localized B0 shimming with a single coil. Proof-of-concept phantom experiments were conducted with such a coil to demonstrate its ability to simultaneously perform these three functions, while maintaining the RF performance, wireless data integrity, and B0 shimming performance. RESULTS: Performing wirelessly controlled shimming of localized B0 inhomogeneities with the coil substantially reduced the B0 root-mean-square error (>70%) and geometric distortions in echo-planar images without degrading the image quality, signal-to-noise ratio (<1.7%), or wireless data throughput (maximum variance = 0.04 Mbps) of the coil. CONCLUSIONS: The RF/wireless coil design can provide a solution for wireless data transfer that can be easily integrated into existing MRI scanners for a variety of applications.

Training with brain-machine interfaces, visuo-tactile feedback and assisted locomotion improves sensorimotor, visceral, and psychological signs in chronic paraplegic patients.

Spinal cord injury (SCI) induces severe deficiencies in sensory-motor and autonomic functions and has a significant negative impact on patients' quality of life. There is currently no systematic rehabilitation technique assuring recovery of the neurological impairments caused by a complete SCI. Here, we report significant clinical improvement in a group of seven chronic SCI patients (six AIS A, one AIS B) following a 28-month, multi-step protocol that combined training with non-invasive brain-machine interfaces, visuo-tactile feedback and assisted locomotion. All patients recovered significant levels of nociceptive sensation below their original SCI (up to 16 dermatomes, average 11 dermatomes), voluntary motor functions (lower-limbs muscle contractions plus multi-joint movements) and partial sensory function for several modalities (proprioception, tactile, pressure, vibration). Patients also recovered partial intestinal, urinary and sexual functions. By the end of the protocol, all patients had their AIS classification upgraded (six from AIS A to C, one from B to C). These improvements translated into significant changes in the patients' quality of life as measured by standardized psychological instruments. Reexamination of one patient that discontinued the protocol after 12 months of training showed that the 16-month break resulted in neurological stagnation and no reclassification. We suggest that our neurorehabilitation protocol, based uniquely on non-invasive technology (therefore necessitating no surgical operation), can become a promising therapy for patients diagnosed with severe paraplegia (AIS A, B), even at the chronic phase of their lesion.

Simultaneous and inherent correction of B0 and eddy-current induced distortions in high-resolution diffusion MRI using reversed polarity gradients and multiplexed sensitivity encoding (RPG-MUSE).

In diffusion MRI (dMRI), static magnetic field (B0) inhomogeneity and time varying gradient eddy currents induce spatial distortions in reconstructed images. These distortions are exacerbated when high spatial resolutions are used, and many field-mapping based correction techniques often only acquire maps of static B0 distortion, which are not adequate for correcting eddy current induced image distortions. This report presents a novel technique, termed RPG-MUSE, for achieving distortion-free high-resolution diffusion MRI by integrating reversed polarity gradients (RPG) into the multi-shot echo planar imaging acquisition scheme used in multiplexed sensitivity encoding (MUSE). By alternating the phase encoding direction between shots in both baseline and diffusion-weighted acquisitions, maps of both static B0 and eddy current induced field inhomogeneities can be inherently derived, without the need for additional data acquisition. Through both 2D and 3D encoded dMRI acquisitions, it is shown that an RPG-MUSE reconstruction can simultaneously achieve high spatial resolution, high spatial fidelity, and subsequently, high accuracy in diffusion metrics.

Structural connectome differences in HIV infection: brain network segregation associated with nadir CD4 cell count.

This study investigated structural brain organization using diffusion tensor imaging (DTI) in 35 HIV-positive and 35 HIV-negative individuals. We used global and nodal graph theory metrics to investigate whether HIV was associated with differences in brain network organization based on fractional anisotropy (FA) and mean diffusivity (MD). Participants also completed a comprehensive neuropsychological testing battery. For global network metrics, HIV-positive individuals displayed a lower FA clustering coefficient relative to HIV-negative individuals. For nodal network metrics, HIV-positive individuals had less MD nodal degree in the left thalamus. Within HIV-positive individuals, the FA global clustering coefficient was positively correlated with nadir CD4 cell count. Across the sample, cognitive performance was negatively correlated with characteristic path length and positively correlated with global efficiency for FA. These results suggest that, despite management with combination antiretroviral therapy, HIV infection is associated with altered structural brain network segregation and thalamic centrality and that low nadir CD4 cell count may be a risk factor. These graph theory metrics may serve as neural biomarkers to identify individuals at risk for HIV-related neurological complications.

Adaptive integrated parallel reception, excitation, and shimming (iPRES-A) with microelectromechanical systems switches.

PURPOSE: Integrated parallel reception, excitation, and shimming coil arrays with N shim loops per radio-frequency (RF) coil element (iPRES(N)) allow an RF current and N direct currents (DC) to flow in each coil element, enabling simultaneous reception/excitation and shimming of highly localized B0 inhomogeneities. The purpose of this work was to reduce the cost and complexity of this design by reducing the number of DC power supplies required by a factor N, while maintaining a high RF and shimming performance. METHODS: In the proposed design, termed adaptive iPRES(N) (iPRES(N)-A), each coil element only requires one DC power supply, but uses microelectromechanical systems switches to adaptively distribute the DC current into the appropriate shim loops to generate the desired magnetic field for B0 shimming. Proof-of-concept phantom experiments with an iPRES(2)-A coil and simulations in the human abdomen with an 8-channel iPRES(4)-A body coil array were performed to demonstrate the advantages of this innovative design. RESULTS: The iPRES(2)-A coil showed no loss in signal-to-noise ratio and provided a much more effective correction of highly localized B0 inhomogeneities and geometric distortions than an equivalent iPRES(1) coil (88.2% vs. 32.2% lower B0 root-mean-square error). The iPRES(4)-A coil array showed a comparable shimming performance as that of an equivalent iPRES(4) coil array (52.6% vs. 54.2% lower B0 root-mean-square error), while only requiring 8 instead of 32 power supplies. CONCLUSION: The iPRES(N)-A design retains the ability of the iPRES(N) design to shim highly localized B0 inhomogeneities, while drastically reducing its cost and complexity. Magn Reson Med 80:371-379, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial.

Cerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted a phase II trial of autologous cord blood (ACB) infusion in children with CP to test whether ACB could improve function (ClinicalTrials.gov, NCT01147653; IND 14360). In this double-blind, placebo-controlled, crossover study of a single intravenous infusion of 1-5 × 107 total nucleated cells per kilogram of ACB, children ages 1 to 6 years with CP were randomly assigned to receive ACB or placebo at baseline, followed by the alternate infusion 1 year later. Motor function and magnetic resonance imaging brain connectivity studies were performed at baseline, 1, and 2 years post-treatment. The primary endpoint was change in motor function 1 year after baseline infusion. Additional analyses were performed at 2 years. Sixty-three children (median age 2.1 years) were randomized to treatment (n = 32) or placebo (n = 31) at baseline. Although there was no difference in mean change in Gross Motor Function Measure-66 (GMFM-66) scores at 1 year between placebo and treated groups, a dosing effect was identified. In an analysis 1 year post-ACB treatment, those who received doses ≥2 × 107 /kg demonstrated significantly greater increases in GMFM-66 scores above those predicted by age and severity, as well as in Peabody Developmental Motor Scales-2 Gross Motor Quotient scores and normalized brain connectivity. Results of this study suggest that appropriately dosed ACB infusion improves brain connectivity and gross motor function in young children with CP. Stem Cells Translational Medicine 2017;6:2071-2078.

3D-MB-MUSE: A robust 3D multi-slab, multi-band and multi-shot reconstruction approach for ultrahigh resolution diffusion MRI.

Recent advances in achieving ultrahigh spatial resolution (e.g. sub-millimeter) diffusion MRI (dMRI) data have proven highly beneficial in characterizing tissue microstructures in organs such as the brain. However, the routine acquisition of in-vivo dMRI data at such high spatial resolutions has been largely prohibited by factors that include prolonged acquisition times, motion induced artifacts, and low SNR. To overcome these limitations, we present here a framework for acquiring and reconstructing 3D multi-slab, multi-band and interleaved multi-shot EPI data, termed 3D-MB-MUSE. Through multi-band excitations, the simultaneous acquisition of multiple 3D slabs enables whole brain dMRI volumes to be acquired in-vivo on a 3 T clinical MRI scanner at high spatial resolution within a reasonably short amount of time. Representing a true 3D model, 3D-MB-MUSE reconstructs an entire 3D multi-band, multi-shot dMRI slab at once while simultaneously accounting for coil sensitivity variations across the slab as well as motion induced artifacts commonly associated with both 3D and multi-shot diffusion imaging. Such a reconstruction fully preserves the SNR advantages of both 3D and multi-shot acquisitions in high resolution dMRI images by removing both motion and aliasing artifacts across multiple dimensions. By enabling ultrahigh resolution dMRI for routine use, the 3D-MB-MUSE framework presented here may prove highly valuable in both clinical and research applications.

Cortical and Subcortical Coordination of Visual Spatial Attention Revealed by Simultaneous EEG-fMRI Recording.

Visual spatial attention has been studied in humans with both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) individually. However, due to the intrinsic limitations of each of these methods used alone, our understanding of the systems-level mechanisms underlying attentional control remains limited. Here, we examined trial-to-trial covariations of concurrently recorded EEG and fMRI in a cued visual spatial attention task in humans, which allowed delineation of both the generators and modulators of the cue-triggered event-related oscillatory brain activity underlying attentional control function. The fMRI activity in visual cortical regions contralateral to the cued direction of attention covaried positively with occipital gamma-band EEG, consistent with activation of cortical regions representing attended locations in space. In contrast, fMRI activity in ipsilateral visual cortical regions covaried inversely with occipital alpha-band oscillations, consistent with attention-related suppression of the irrelevant hemispace. Moreover, the pulvinar nucleus of the thalamus covaried with both of these spatially specific, attention-related, oscillatory EEG modulations. Because the pulvinar's neuroanatomical geometry makes it unlikely to be a direct generator of the scalp-recorded EEG, these covariational patterns appear to reflect the pulvinar's role as a regulatory control structure, sending spatially specific signals to modulate visual cortex excitability proactively. Together, these combined EEG/fMRI results illuminate the dynamically interacting cortical and subcortical processes underlying spatial attention, providing important insight not realizable using either method alone.SIGNIFICANCE STATEMENT Noninvasive recordings of changes in the brain's blood flow using functional magnetic resonance imaging and electrical activity using electroencephalography in humans have individually shown that shifting attention to a location in space produces spatially specific changes in visual cortex activity in anticipation of a stimulus. The mechanisms controlling these attention-related modulations of sensory cortex, however, are poorly understood. Here, we recorded these two complementary measures of brain activity simultaneously and examined their trial-to-trial covariations to gain insight into these attentional control mechanisms. This multi-methodological approach revealed the attention-related coordination of visual cortex modulation by the subcortical pulvinar nucleus of the thalamus while also disentangling the mechanisms underlying the attentional enhancement of relevant stimulus input and those underlying the concurrent suppression of irrelevant input.