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.

Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study.

BACKGROUND: Growing evidence indicates that anhedonia is a multifaceted construct. This study examined the possibility of identifying subgroups of people with anhedonia using multiple reward-related measures to provide greater understanding the Research Domain Criteria's Positive Valence Systems Domain and pathways for developing treatments. METHODS: Latent profile analysis of baseline data from a study that examined the effects of a novel kappa opioid receptor (KOR) antagonist drug on measures and biomarkers associated with anhedonia was used to identify subgroups. Measures included ventral striatal activation during the Monetary Incentive Delay task, response bias in the Probabilistic Reward Task, reward valuation scores from the Effort-Expenditure for Rewards Task, and scores from reward-related self-report measures. RESULTS: Two subgroups were identified, which differed on self-report measures of reward. Participants in the subgroup reporting more anhedonia also reported more depression and had greater illness severity and functional impairments. Graphs of change with treatment showed a trend for the less severe subgroup to demonstrate higher response to KOR antagonist treatment on the neuroimaging measure, probabilistic reward task, and ratings of functioning; the subgroup with greater severity showed a trend for higher treatment response on reward-related self-report measures. LIMITATIONS: The main limitations include the small sample size and exploratory nature of analyses. CONCLUSIONS: Evidence of possible dissociation between self-reported measures of anhedonia and other measures with respect to treatment response emerged. These results highlight the importance for future research to consider severity of self-reported reward-related deficits and how the relationship across measurement methods may vary with severity.

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.

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.

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.

Changes in the geometry and robustness of diffusion tensor imaging networks: Secondary analysis from a randomized controlled trial of young autistic children receiving an umbilical cord blood infusion.

Diffusion tensor imaging (DTI) has been used as an outcome measure in clinical trials for several psychiatric disorders but has rarely been explored in autism clinical trials. This is despite a large body of research suggesting altered white matter structure in autistic individuals. The current study is a secondary analysis of changes in white matter connectivity from a double-blind placebo-control trial of a single intravenous cord blood infusion in 2-7-year-old autistic children (1). Both clinical assessments and DTI were collected at baseline and 6 months after infusion. This study used two measures of white matter connectivity: change in node-to-node connectivity as measured through DTI streamlines and a novel measure of feedback network connectivity, Ollivier-Ricci curvature (ORC). ORC is a network measure which considers both local and global connectivity to assess the robustness of any given pathway. Using both the streamline and ORC analyses, we found reorganization of white matter pathways in predominantly frontal and temporal brain networks in autistic children who received umbilical cord blood treatment versus those who received a placebo. By looking at changes in network robustness, this study examined not only the direct, physical changes in connectivity, but changes with respect to the whole brain network. Together, these results suggest the use of DTI and ORC should be further explored as a potential biomarker in future autism clinical trials. These results, however, should not be interpreted as evidence for the efficacy of cord blood for improving clinical outcomes in autism. This paper presents a secondary analysis using data from a clinical trial that was prospectively registered with ClinicalTrials.gov(NCT02847182).

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.

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.

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.

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.

Measuring robustness of brain networks in autism spectrum disorder with Ricci curvature.

Ollivier-Ricci curvature is a method for measuring the robustness of connections in a network. In this work, we use curvature to measure changes in robustness of brain networks in children with autism spectrum disorder (ASD). In an open label clinical trials, participants with ASD were administered a single infusion of autologous umbilical cord blood and, as part of their clinical outcome measures, were imaged with diffusion MRI before and after the infusion. By using Ricci curvature to measure changes in robustness, we quantified both local and global changes in the brain networks and their potential relationship with the infusion. Our results find changes in the curvature of the connections between regions associated with ASD that were not detected via traditional brain network analysis.

A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder.

OBJECTIVE: To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD). STUDY DESIGN: This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion. RESULTS: CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power. CONCLUSIONS: Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.

A randomized proof-of-mechanism trial applying the 'fast-fail' approach to evaluating κ-opioid antagonism as a treatment for anhedonia.

The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach.

Magnetic resonance imaging volumetric analysis in patients with Alternating hemiplegia of childhood: A pilot study.

Quantitative MRI is increasingly being used as a biomarker in neurological disorders. Cerebellar atrophy occurs in some Alternating Hemiplegia of Childhood (AHC) patients. However, it is not known if cerebellar atrophy can be a potential biomarker in AHC or if quantitative MRI is a reliable method to address this question. Here we determine the reproducibility of an MRI-volumetrics method to investigate brain volumes in AHC and apply it to a population of 14 consecutive AHC patients (ages 4-11 years). We studied method reproducibility in the first 11 patients and then performed correlation of cerebellar volumes, relative to published normal population means, with age in all 14. We used FreeSurfer 6.0.0 to automatically segment MRI images, then performed manual resegmentation correction by two different observers. No significant differences were observed in any of ten brain regions between the two reviewers: p > .591 and interclass Correlation Coefficient (ICC) ≥0.975 in all comparisons. Additionally, there were no significant differences between the means of the two reviewers and the automatic segmentation values: p ≥ .106 and ICC ≥0.994 in all comparisons. We found a negative correlation between cerebellar volume and age (R = -0.631, p = .037), even though only one patient showed any cerebellar atrophy upon formal readings of the MRIs by neuroradiology. Sample size did not allow us to rule out potential confounding variables. Thus, findings from this cross-sectional study should be considered as exploratory. Our study supports the prospective investigation of quantitative MRI-volumetrics of the cerebellum as a potential biomarker in AHC.

White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Trial Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social communication deficits and the presence of restricted interests and repetitive behaviors. We have previously reported significant improvements in behavior, including increased social functioning, improved communication abilities, and decreased clinical symptoms in children with ASD, following treatment with a single infusion of autologous cord blood in a phase I open-label trial. In the current study, we aimed to understand whether these improvements were associated with concurrent changes in brain structural connectivity. Twenty-five 2- to 6-year-old children with ASD participated in this trial. Clinical outcome measures included the Vineland Adaptive Behavior Scales-II Socialization Subscale, Expressive One-Word Picture Vocabulary Test-4, and the Clinical Global Impression-Improvement Scale. Structural connectivity was measured at baseline and at 6 months in a subset of 19 children with 25-direction diffusion tensor imaging and deterministic tractography. Behavioral improvements were associated with increased white matter connectivity in frontal, temporal, and subcortical regions (hippocampus and basal ganglia) that have been previously shown to show anatomical, connectivity, and functional abnormalities in ASD. The current results suggest that improvements in social communication skills and a reduction in symptoms in children with ASD following treatment with autologous cord blood infusion were associated with increased structural connectivity in brain networks supporting social, communication, and language abilities. Stem Cells Translational Medicine 2019;8:138&10.

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.