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PURPOSE: Fetal brain Magnetic Resonance Imaging suffers from unpredictable and unconstrained fetal motion that causes severe image artifacts even with half-Fourier single-shot fast spin echo (HASTE) readouts. This work presents the implementation of a closed-loop pipeline that automatically detects and reacquires HASTE images that were degraded by fetal motion without any human interaction. METHODS: A convolutional neural network that performs automatic image quality assessment (IQA) was run on an external GPU-equipped computer that was connected to the internal network of the MRI scanner. The modified HASTE pulse sequence sent each image to the external computer, where the IQA convolutional neural network evaluated it, and then the IQA score was sent back to the sequence. At the end of the HASTE stack, the IQA scores from all the slices were sorted, and only slices with the lowest scores (corresponding to the slices with worst image quality) were reacquired. RESULTS: The closed-loop HASTE acquisition framework was tested on 10 pregnant mothers, for a total of 73 acquisitions of our modified HASTE sequence. The IQA convolutional neural network, which was successfully employed by our modified sequence in real time, achieved an accuracy of 85.2% and area under the receiver operator characteristic of 0.899. CONCLUSION: The proposed acquisition/reconstruction pipeline was shown to successfully identify and automatically reacquire only the motion degraded fetal brain HASTE slices in the prescribed stack. This minimizes the overall time spent on HASTE acquisitions by avoiding the need to repeat the entire stack if only few slices in the stack are motion-degraded.

OBJECTIVE Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. METHODS From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. RESULTS HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p

Objective To assess the ability of high‐density Electroencephalography (HD‐EEG) and magnetoencephalography (MEG) to localize interictal ripples, distinguish between ripples co‐occurring with spikes (ripples‐on‐spike) and independent from spikes (ripples‐alone), and evaluate their localizing value as biomarkers of epileptogenicity in children with medically refractory epilepsy. Methods We retrospectively studied 20 children who underwent epilepsy surgery. We identified ripples on HD‐EEG and MEG data, localized their generators, and compared them with intracranial EEG (icEEG) ripples. When ripples and spikes co‐occurred, we performed source imaging distinctly on the data above 80 Hz (to localize ripples) and below 70 Hz (to localize spikes). We assessed whether missed resection of ripple sources predicted poor outcome, separately for ripples‐on‐spikes and ripples‐alone. Similarly, predictive value of spikes was calculated. Results We observed scalp ripples in 16 patients (10 good outcome). Ripple sources were highly concordant to the icEEG ripples (HD‐EEG concordance: 79%; MEG: 83%). When ripples and spikes co‐occurred, their sources were spatially distinct in 83‐84% of the cases. Removing the sources of ripples‐on‐spikes predicted good outcome with 90% accuracy for HD‐EEG (P = 0.008) and 86% for MEG (P = 0.044). Conversely, removing ripples‐alone did not predict outcome. Resection of spike sources (generated at the same time as ripples) predicted good outcome for HD‐EEG (P = 0.036; accuracy = 87%), while did not reach significance for MEG (P = 0.1; accuracy = 80%). Interpretation HD‐EEG and MEG localize interictal ripples with high precision in children with refractory epilepsy. Scalp ripples‐on‐spikes are prognostic, noninvasive biomarkers of epileptogenicity, since removing their cortical generators predicts good outcome. Conversely, scalp ripples‐alone are most likely generated by non‐epileptogenic areas.

Quantification of proton magnetic resonance spectroscopy (1 H-MRS) data is commonly performed by referencing the ratio of the signal from one metabolite, or metabolite group, to that of another, or to the water signal. Both approaches have drawbacks: ratios of two metabolites can be difficult to interpret because study effects may be driven by either metabolite, and water-referenced data must be corrected for partial volume and relaxation effects in the water signal. Here, we introduce combined reference (CRef) analysis, which compensates for both limitations. In this approach, metabolites are referenced to the combined signal of several reference metabolites or metabolite groups. The approach does not require the corrections necessary for water scaling and produces results that are less sensitive to the variation of any single reference signal, thereby aiding the interpretation of results. We demonstrate CRef analysis using 202 1 H-MRS acquisitions from the brains of 140 infants, scanned at approximately 1 and 3 months of age. We show that the combined signal of seven reference metabolites or metabolite groups is highly correlated with the water signal, corrected for partial volume and relaxation effects associated with cerebral spinal fluid. We also show that the combined reference signal is equally or more uniform across subjects than the reference signals from single metabolites or metabolite groups. We use CRef analysis to quantify metabolite concentration changes during the first several months of life in typically developing infants.

In fetal-brain MRI, head-pose changes between prescription and acquisition present a challenge to obtaining the standard sagittal, coronal and axial views essential to clinical assessment. As motion limits acquisitions to thick slices that preclude retrospective resampling, technologists repeat ~55-second stack-of-slices scans (HASTE) with incrementally reoriented field of view numerous times, deducing the head pose from previous stacks. To address this inefficient workflow, we propose a robust head-pose detection algorithm using full-uterus scout scans (EPI) which take ~5 seconds to acquire. Our ~2-second procedure automatically locates the fetal brain and eyes, which we derive from maximally stable extremal regions (MSERs). The success rate of the method exceeds 94% in the third trimester, outperforming a trained technologist by up to 20%. The pipeline may be used to automatically orient the anatomical sequence, removing the need to estimate the head pose from 2D views and reducing delays during which motion can occur., Comment: 19 pages, 10 figures, 2 tables, fetal MRI, head-pose detection, MSER, scan automation, scan prescription, slice positioning, final published version

Objective In patients with medically refractory epilepsy (MRE), interictal ripples (80-250Hz) are observed in large brain areas whose resection may be unnecessary for seizure freedom. This limits their utility as epilepsy biomarkers for surgery. We assessed the spatiotemporal propagation of interictal ripples on intracranial electroencephalography (iEEG) in children with MRE, compared it with the propagation of spikes, identified ripples that initiated propagation (onset-ripples), and evaluated their clinical value as epilepsy biomarkers. Methods Twenty-seven children who underwent epilepsy surgery were studied. We identified propagation sequences of ripples and spikes across multiple iEEG contacts and calculated each ripple or spike latency from the propagation onset. We classified ripples and spikes into categories (ie, onset, spread, and isolated) based on their spatiotemporal characteristics and correlated their mean rate inside and outside resection with outcome (good outcome, Engel 1 versus poor outcome, Engel≥2). We determined, as onset-zone, spread-zone, and isolated-zone, the areas generating the corresponding ripple or spike category and evaluated the predictive value of their resection. Results We observed ripple propagation in all patients and spike propagation in 25 patients. Mean rate of onset-ripples inside resection predicted the outcome (odds ratio = 5.37; p = 0.02) and correlated with Engel class (rho = -0.55; p = 0.003). Resection of the onset-ripple-zone was associated with good outcome (p = 0.047). No association was found for the spread-ripple-zone, isolated-ripple-zone, or any spike-zone. Interpretation Interictal ripples propagate across iEEG contacts in children with MRE. The association between the onset-ripple-zone resection and good outcome indicates that onset-ripples are promising epilepsy biomarkers, which estimate the epileptogenic tissue better than spread-ripples or onset-spikes. Ann Neurol 2018;84:331-346.

KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate-binding loop motif and motor-like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.

Background Given the central role of the thalamus in motor, sensory, and cognitive development, methods to study emerging thalamocortical connectivity in early infancy are of great interest. Purpose To determine the feasibility of performing probabilistic tractography-based thalamic parcellation (PTbTP) in typically developing (TD) neonates and to compare the results with a pilot sample of neonates with congenital heart disease (CHD). Study type Institutional Review Board (IRB)-approved cross-sectional study. Model We prospectively recruited 20 TD neonates and five CHD neonates (imaged preoperatively). Field strength/sequence MRI was performed at 3.0T including diffusion-weighted imaging (DWI) and 3D magnetization prepared rapid gradient-echo (MPRAGE). Assessment A radiologist and trained research assistants segmented the thalamus and seven cortical targets for each hemisphere. Using the thalami as seeds and the cortical labels as targets, FSL library tools were used to generate probabilistic tracts. A Hierarchical Dirichlet Process algorithm was then used for clustering analysis. A radiologist qualitatively assessed the results of clustering. Quantitative analyses were also performed. Statistical tests We summarized the demographic data and results of clustering with descriptive statistics. Linear regressions covarying for gestational age were used to compare groups. Results In 17 of 20 TD neonates, we identified five connectivity-determined clusters, which correlate with known thalamic nuclei and subnuclei. In four neonates with CHD we observed a spectrum of abnormalities including fewer and disorganized clusters or small supernumerary clusters (up to seven per thalamus). After covarying for differences in corrected gestational age (cGA), the fractional anisotropy (FA), volume, and normalized thalamic volume were significantly lower in CHD neonates (P Data conclusions Using PTbTP clusters, correlating well with the location and connectivity of known thalamic nuclei, were identified in TD neonates. Differences in thalamic clustering outputs were identified in four neonates with CHD, raising concern for disordered thalamic connectivity. PTbTP is feasible in TD and CHD neonates. Preliminary findings suggest the prenatal origins of altered connectivity in CHD. Level of evidence 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1626-1637.

Diffusion imaging is critical for detecting acute brain injury. However, normal apparent diffusion coefficient (ADC) maps change rapidly in early childhood, making abnormality detection difficult. In this article, we explored clinical PACS and electronic healthcare records (EHR) to create age-specific ADC atlases for clinical radiology reference. Using the EHR and three rounds of multiexpert reviews, we found ADC maps from 201 children 0-6 years of age scanned between 2006 and 2013 who had brain MRIs with no reported abnormalities and normal clinical evaluations 2+ years later. These images were grouped in 10 age bins, densely sampling the first 1 year of life (5 bins, including neonates and 4 quarters) and representing the 1-6 year age range (an age bin per year). Unbiased group-wise registration was used to construct ADC atlases for 10 age bins. We used the atlases to quantify (a) cross-sectional normative ADC variations; (b) spatiotemporal heterogeneous ADC changes; and (c) spatiotemporal heterogeneous volumetric changes. The quantified age-specific whole-brain and region-wise ADC values were compared to those from age-matched individual subjects in our study and in multiple existing independent studies. The significance of this study is that we have shown that clinically acquired images can be used to construct normative age-specific atlases. These first of their kind age-specific normative ADC atlases quantitatively characterize changes of myelination-related water diffusion in the first 6 years of life. The quantified voxel-wise spatiotemporal ADC variations provide standard references to assist radiologists toward more objective interpretation of abnormalities in clinical images. Our atlases are available at https://www.nitrc.org/projects/mgh_adcatlases. Hum Brain Mapp 38:3052-3068, 2017. © 2017 Wiley Periodicals, Inc.

Purpose: We generate 12 models from 4 pregnant individuals to evaluate individual differences in local specific absorption rate (SAR) for differing body habitus and fetal and maternal positions. Methods: Structural MR images from 4 pregnant subjects (including supine and left-lateral maternal positions) were manually segmented to create 12 body models by rotating the fetus, modifying the fat content, and altering the maternal arm position in 1 of the subjects. Electromagnetic simulations modeled at 3 Tesla determined the average and peak local SAR in the maternal trunk, fetus, fetal brain, and amniotic fluid. Results: We observed a significant range of fetal and maternal peak local SAR across the models (maternal trunk: 19.14-44.03 watts/kg, fetus: 9.93-18.79 watts/kg, fetal brain 3.36-10.3 watts/kg). We found that maternal body habitus changes introduced a significant variation in the maternal peak local SAR but not the fetal local SAR. However, the maternal position (either rotating the mother to left–lateral position or altering the arm position) introduced changes in fetal peak local SAR (range: 11.9-17.9 watts/kg). Rotating the fetus also introduced variation in the fetal and fetal brain peak local SAR. Conclusion: The observed variation in SAR emphasizes the need for more anatomical models to enable better safety management of individuals during fetal MRI, including a wider range of gestational ages., National Institutes of Health (Grants U01 HD087211, R01 EB017337)

Char syndrome is characterized by persistent patent ductus arteriosus (PDA) associated with hand-skeletal abnormalities and distinctive facial dysmorphism. Pathogenic variants in the transcription factor gene TFAP2B have been shown to cause Char syndrome; however, there is significant phenotypic variability linked to variant location. Here, we report a pediatric patient with a novel de novo variant in the fifth exon of TFAP2B, c.917C > T (p.Thr306Met), who presented with PDA, patent foramen ovale, postaxial polydactyly of the left fifth toe and clinodactyly of the left fourth toe, sensorineural hearing loss, scoliosis, dental anomalies, and central diabetes insipidus (CDI). CDI, scoliosis, and hearing loss have not previously been reported in a patient with Char syndrome, and while the association may be coincidental, this report expands the genotypes and potentially phenotypes associated with this syndrome.

One set of missense mutations in the neuron specific beta tubulin isotype 3 (TUBB3) has been reported to cause malformations of cortical development (MCD), while a second set has been reported to cause isolated or syndromic Congenital Fibrosis of the Extraocular Muscles type 3 (CFEOM3). Because TUBB3 mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently. Here, however, we report two novel de novo heterozygous TUBB3 amino acid substitutions, G71R and G98S, in four patients with both MCD and syndromic CFEOM3. These patients present with moderately severe CFEOM3, nystagmus, torticollis, and developmental delay, and have intellectual and social disabilities. Neuroimaging reveals defective cortical gyration, as well as hypoplasia or agenesis of the corpus callosum and anterior commissure, malformations of hippocampi, thalami, basal ganglia and cerebella, and brainstem and cranial nerve hypoplasia. These new TUBB3 substitutions meld the two previously distinct TUBB3-associated phenotypes, and implicate similar microtubule dysfunction underlying both.

© 2017 International Society for Magnetic Resonance in Medicine Purpose: This article introduces a constrained imaging method based on low-rank and subspace modeling to improve the accuracy and speed of MR fingerprinting (MRF). Theory and Methods: A new model-based imaging method is developed for MRF to reconstruct high-quality time-series images and accurate tissue parameter maps (e.g., T1, T2, and spin density maps). Specifically, the proposed method exploits low-rank approximations of MRF time-series images, and further enforces temporal subspace constraints to capture magnetization dynamics. This allows the time-series image reconstruction problem to be formulated as a simple linear least-squares problem, which enables efficient computation. After image reconstruction, tissue parameter maps are estimated via dictionary-based pattern matching, as in the conventional approach. Results: The effectiveness of the proposed method was evaluated with in vivo experiments. Compared with the conventional MRF reconstruction, the proposed method reconstructs time-series images with significantly reduced aliasing artifacts and noise contamination. Although the conventional approach exhibits some robustness to these corruptions, the improved time-series image reconstruction in turn provides more accurate tissue parameter maps. The improvement is pronounced especially when the acquisition time becomes short. Conclusions: The proposed method significantly improves the accuracy of MRF, and also reduces data acquisition time. Magn Reson Med 79:933–942, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Purpose To enable highly accelerated RARE/Turbo Spin Echo (TSE) imaging using Simultaneous MultiSlice (SMS) Wave-CAIPI acquisition with reduced g-factor penalty. Methods SMS Wave-CAIPI incurs slice shifts across simultaneously excited slices while playing sinusoidal gradient waveforms during the readout of each encoding line. This results in an efficient k-space coverage that spreads aliasing in all three dimensions to fully harness the encoding power of coil sensitivities. The novel MultiPINS radiofrequency (RF) pulses dramatically reduce the power deposition of multiband (MB) refocusing pulse, thus allowing high MB factors within the Specific Absorption Rate (SAR) limit. Results Wave-CAIPI acquisition with MultiPINS permits whole brain coverage with 1 mm isotropic resolution in 70 s at effective MB factor 13, with maximum and average g-factor penalties of gmax = 1.34 and gavg = 1.12, and without √R penalty. With blipped-CAIPI, the g-factor performance was degraded to gmax = 3.24 and gavg = 1.42; a 2.4-fold increase in gmax relative to Wave-CAIPI. At this MB factor, the SAR of the MultiBand and PINS pulses are 4.2 and 1.9 times that of the MultiPINS pulse, while the peak RF power are 19.4 and 3.9 times higher. Conclusion Combination of the two technologies, Wave-CAIPI and MultiPINS pulse, enables highly accelerated RARE/TSE imaging with low SNR penalty at reduced SAR. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. Magn Reson Med 73:929–938, 2015. © 2014 Wiley Periodicals, Inc.

Purpose To introduce the wave-CAIPI (controlled aliasing in parallel imaging) acquisition and reconstruction technique for highly accelerated 3D imaging with negligible g-factor and artifact penalties. Methods The wave-CAIPI 3D acquisition involves playing sinusoidal and gradients during the readout of each encoding line while modifying the 3D phase encoding strategy to incur interslice shifts as in 2D-CAIPI acquisitions. The resulting acquisition spreads the aliasing evenly in all spatial directions, thereby taking full advantage of 3D coil sensitivity distribution. By expressing the voxel spreading effect as a convolution in image space, an efficient reconstruction scheme that does not require data gridding is proposed. Rapid acquisition and high-quality image reconstruction with wave-CAIPI is demonstrated for high-resolution magnitude and phase imaging and quantitative susceptibility mapping. Results Wave-CAIPI enables full-brain gradient echo acquisition at 1 mm isotropic voxel size and R = 3 × 3 acceleration with maximum g-factors of 1.08 at 3T and 1.05 at 7T. Relative to the other advanced Cartesian encoding strategies (2D-CAIPI and bunched phase encoding) wave-CAIPI yields up to two-fold reduction in maximum g-factor for nine-fold acceleration at both field strengths. Conclusion Wave-CAIPI allows highly accelerated 3D acquisitions with low artifact and negligible g-factor penalties, and may facilitate clinical application of high-resolution volumetric imaging. Magn Reson Med 73:2152–2162, 2015. © 2014 Wiley Periodicals, Inc.

Objective Although there is growing awareness of the long-term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long-term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies. Methods A weight drop rmTBI model was used that results in cognitive deficits without loss of consciousness, seizures, or gross or microscopic evidence of brain damage. Cognitive function was assessed using a Morris water maze (MWM) paradigm. Immunostaining and enzyme-linked immunosorbent assay (ELISA) were used to assess amyloid β deposition and tau hyperphosphorylation. Brain volume and white matter integrity were assessed by magnetic resonance imaging (MRI). Results Mice subjected to rmTBI daily or weekly but not biweekly or monthly had persistent cognitive deficits as long as 1 year after injuries. Long-term cognitive deficits were associated with increased astrocytosis but not tau phosphorylation or amyloid β (by ELISA); plaques or tangles (by immunohistochemistry); or brain volume loss or changes in white matter integrity (by MRI). APOE4 was not associated with worse MWM performance after rmTBI. Interpretation Within the vulnerable time period between injuries, rmTBI produces long-term cognitive deficits independent of increased amyloid β or tau phosphorylation. In this model, cognitive outcome is not influenced by APOE4 status. The data have implications for the long-term mental health of athletes who suffer multiple concussions. Ann Neurol 2013;74:65–75

Mutations in SCN2A gene cause a variety of epilepsy syndromes. We report a novel SCN2A-associated epilepsy phenotype in monozygotic twins with tonic seizures soon after birth and a suppression-burst electroencephalography (EEG) pattern. We reviewed the medical records, EEG tracings, magnetic resonance imaging (MRI), and neuropathologic findings, and performed whole genome sequencing (WGS) on Twin B's DNA and Sanger sequencing (SS) on candidate gene mutations. Extensive neurometabolic evaluation and early neuroimaging studies were normal. Twin A died of an iatrogenic cause at 2 weeks of life. His neuropathologic examination was remarkable for dentate-olivary dysplasia and granule cell dispersion of the dentate gyrus. Twin B became seizure free at 8 months and was off antiepileptic drugs by 2 years. His brain MRI, normal at 2 months, revealed evolving brainstem and basal ganglia abnormalities at 8 and 15 months that resolved by 20 months. At 2.5 years, Twin B demonstrated significant developmental delay. Twin B's WGS revealed a heterozygous variant c.788C>T predicted to cause p.Ala263Val change in SCN2A and confirmed to be de novo in both twins by SS. In conclusion, we have identified a de novo SCN2A mutation as the etiology for Ohtahara syndrome in monozygotic twins associated with a unique dentate-olivary dysplasia in the deceased twin.

© 2017 International Society for Magnetic Resonance in Medicine Purpose: Subject motion may cause errors in estimates of blood T2 when using the T2-relaxation under spin tagging (TRUST) technique on noncompliant subjects like neonates. By incorporating 3D volume navigators (vNavs) into the TRUST pulse sequence, independent measurements of motion during scanning permit evaluation of these errors. Methods: The effects of integrated vNavs on TRUST-based T2 estimates were evaluated using simulations and in vivo subject data. Two subjects were scanned with the TRUST+vNav sequence during prescribed movements. Mean motion scores were derived from vNavs and TRUST images, along with a metric of exponential fit quality. Regression analysis was performed between T2 estimates and mean motion scores. Also, motion scores were determined from independent neonatal scans. Results: vNavs negligibly affected venous blood T2 estimates and better detected subject motion than fit quality metrics. Regression analysis showed that T2 is biased upward by 4.1 ms per 1 mm of mean motion score. During neonatal scans, mean motion scores of 0.6 to 2.0 mm were detected. Conclusion: Motion during TRUST causes an overestimate of T2, which suggests a cautious approach when comparing TRUST-based cerebral oxygenation measurements of noncompliant subjects. Magn Reson Med 78:2283–2289, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Copyright © 2016 John Wiley & Sons, Ltd. Quantitative susceptibility mapping (QSM) estimates the underlying tissue magnetic susceptibility from the gradient echo (GRE) phase signal through background phase removal and dipole inversion steps. Each of these steps typically requires the solution of an ill-posed inverse problem and thus necessitates additional regularization. Recently developed single-step QSM algorithms directly relate the unprocessed GRE phase to the unknown susceptibility distribution, thereby requiring the solution of a single inverse problem. In this work, we show that such a holistic approach provides susceptibility estimation with artifact mitigation and develop efficient algorithms that involve simple analytical solutions for all of the optimization steps. Our methods employ total variation (TV) and total generalized variation (TGV) to jointly perform the background removal and dipole inversion in a single step. Using multiple spherical mean value (SMV) kernels of varying radii permits high-fidelity background removal whilst retaining the phase information in the cortex. Using numerical simulations, we demonstrate that the proposed single-step methods reduce the reconstruction error by up to 66% relative to the multi-step methods that involve SMV background filtering with the same number of SMV kernels, followed by TV- or TGV-regularized dipole inversion. In vivo single-step experiments demonstrate a dramatic reduction in dipole streaking artifacts and improved homogeneity of image contrast. These acquisitions employ the rapid three-dimensional echo planar imaging (3D EPI) and Wave-CAIPI (controlled aliasing in parallel imaging) trajectories for signal-to-noise ratio-efficient whole-brain imaging. Herein, we also demonstrate the multi-echo capability of the Wave-CAIPI sequence for the first time, and introduce an automated, phase-sensitive coil sensitivity estimation scheme based on a 4-s calibration acquisition. Copyright © 2016 John Wiley & Sons, Ltd.

© 2017 International Society for Magnetic Resonance in Medicine Purpose: To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. Materials and Methods: The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. Results: The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P < 0.01) and volume overlap and distance between region boundaries measures were significantly improved (P < 0.01). Conclusion: The proposed approach to align MRI time series enables more accurate quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs. Level of Evidence: 1. Technical Efficacy: Stage 1. J. MAGN. RESON. IMAGING 2017;46:403–412.

Structural and functional magnetic resonance imaging (fMRI) has been used increasingly to investigate typical and atypical brain development. However, in contrast to studies in school-aged children and adults, MRI research in young pediatric age groups is less common. Practical and technical challenges occur when imaging infants and children, which presents clinicians and research teams with a unique set of problems. These include procedural difficulties (e.g., participant anxiety or movement restrictions), technical obstacles (e.g., availability of child-appropriate equipment or pediatric MR head coils), and the challenge of choosing the most appropriate analysis methods for pediatric imaging data. Here, we summarize and review pediatric imaging and analysis tools and present neuroimaging protocols for young nonsedated children and infants, including guidelines and procedures that have been successfully implemented in research protocols across several research sites.

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.

Tuberous sclerosis complex (TSC) is a genetic disease characterized by the presence of hamartomatous lesions in multiple organs and cortical tubers in the brain. The majority of patients with TSC have epilepsy, although the mechanisms underlying epileptogenesis remain unknown. Tubers are traditionally thought to be stable lesions that result from abnormal corticogenesis in early fetal development. Recently, cystlike tubers have been identified in nearly half of patients with TSC, although the spectrum and natural history of these lesions remains unknown. Herein we report eight children with a high burden of cystlike tubers and present detailed clinical information on two children with documented progression. We also report neuropathologic findings of one of the cystlike cortical tubers resected in epilepsy surgery. These cases support the notion that cystlike tubers in TSC are not static lesions and can exhibit evolving characteristics over time. Further work evaluating how these lesions relate to epileptogenesis needs to be done.

Neuroimaging is essential in the work-up of patients with intractable epilepsy. In pediatric patients with medically refractory epilepsy, cortical dysplasias account for a large percentage of the epileptogenic substrate. Unfortunately, these are also the most subtle lesions to identify. For this reason, there has been ongoing interest in utilizing new advanced magnetic resonance imaging (MRI) techniques to improve the ability to identify, diagnose, characterize, and delineate cortical dysplasias. Technologic gains such as multichannel coils (32 phased array and beyond) and higher field strengths (3T, 7T, and greater) coupled with newer imaging sequences such as arterial spin labeling (ASL), susceptibility weighted imaging (SWI) and diffusion tensor/spectrum imaging (DTI/DSI) are likely to increase yield. Improved MRI techniques coupled with a multimodality approach including magnetoencephalography (MEG), positron emission tomography (PET), and other techniques will increase sensitivity and specificity for identifying cortical dysplasias.

Objective. Patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often show ictal and interictal propagation of epileptiform EEG activity to the ipsilateral temporal neocortex, the ipsilateral frontal lobe or the contralateral hippocampus, although structural MRI only shows unilateral involvement of the hippocampal formation. We used whole-head diffusion Tensor Imaging (DTI) to delineate a network that facilitates propagation of interictal epileptiform and seizure activity in this patient group. Methods. Isotropic 2 mm DTI was performed at 3 Tesla in 12 patients with medically intractable left TLE due to HS and compared to 12 controls. Whole-brain maps of fractional anisotropy (FA) were compared using a voxel based t-test to search for regions affected in patients with HS. This preliminary analysis was complementary to a set of anatomically guided region of interest (ROI) analyses that were manually defined on each individual’s FA map. Results. Left HS patients showed FA decreases in the temporal lobe white matter bilaterally, the ipsilateral frontal lobe white matter (WM) and in the genu and trunk of the corpus callosum. ROI analysis identified a significant FA decrease in left HS subjects in the affected hippocampus, WM of the ipsilateral parahippocampal gyrus and the genu and trunk of the corpus callosum. Conclusion. WM alterations occur bilaterally in the temporal lobe and in the ipsilateral superior frontal gyrus in left HS. The etiology and significance of these changes are unclear but the role of these regions in epileptogenesis and for pathways of epileptic spread should be further investigated.

With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD-NIRS) measures of cerebral tissue oxygenation (StO(2)) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBF(ix)) to test the validity of the CBV-CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO(2)) with or without the CBF(ix) measurement. We measured 11 premature neonates (28-34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO(2) during the first six weeks of life while CBV remains stable, and a steady increase in CBF(ix). rCMRO(2) estimated from FD-NIRS remains constant but shows wide interindividual variability. rCMRO(2) calculated from FD-NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD-NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO(2), CBF, and rCMRO(2) in the premature brain, facilitating individual follow-up and comparison among patients. A stable CBV-CBF relationship may not be valid for premature neonates.

Phased-array imaging at 1.5 and 3 T significantly improves image quality compared with that in routine 1.5-T head coil studies. These improvements significantly increase lesion detection in patients with focal epilepsy. Semiautomated image-analysis techniques have the potential to improve lesion detection, assess lesion burden more accurately, characterize cortical abnormalities, and determine the location and extent of associated cortical and deep gray nuclei involvement. With increasing interest in understanding the role white matter plays in epileptogenesis and seizure propagation, diffusion tensor imaging may yield useful information about changes in white matter organization. Our current multimodality imaging combines these structural imaging advances with coregistered neurophysiological information obtained with magnetoencephalography and with simultaneous EEG recordings. Our initial experience suggests that multimodality imaging will improve our ability to detect and define the extent of epileptogenic lesions.

Mutations in the X-linked doublecortin gene appear in many sporadic cases of double cortex (DC; also known as subcortical band heterotopia), a neuronal migration disorder causing epilepsy and mental retardation. The purpose of this study was to examine why a significant percentage of sporadic DC patients had been found not to harbor doublecortin mutations and to determine whether clinical features or magnetic resonance imaging scan appearance could distinguish between patients with and without doublecortin mutations. Magnetic resonance imaging scan analysis differentiated patients into the following four groups: anterior biased/global DC with doublecortin mutation (16 of 30; 53%), anterior biased/global DC without mutation (8 of 30; 27%), posterior biased DC without mutation (3 of 30; 10%), and limited/unilateral DC without mutation (3 of 30; 10%). The presence of these atypical phenotypes suggests that other genetic loci or mosaicism at the doublecortin locus may be responsible for this diversity of DC cases.

Summary: Purpose: Transient increased T2 signal in the splenium of the corpus callosum after seizures has been reported and sometimes attributed to a postulated toxicity of anticonvulsant medications (AEDs). Methods: We describe two patients with bitemporal epilepsy. Results: Transiently increased T2 signal (in one) and decreased apparent diffusion coefficient (ADC) (in both) in the splenium appeared to be related directly to acute seizures. Conclusions: These cases illustrate an unusual acute postictal imaging finding, highlight involvement of an important commissural pathway, and suggest that seizures per se, and not their treatment, are the cause of transient white-matter abnormalities in these cases. Key Words: Splenium—Diffusion-weighted imaging—Magnetic resonance imaging. Magnetic resonance imaging (MRI) has revolutionized the evaluation of patients with seizures over the last two decades. Most MRI is obtained interictally to search for an underlying structural basis for epileptic discharge, recent attention has focused on the potential of MRI to reveal transient physiologic changes associated with abnormal neuronal activity. Here we present two patients who manifested transient changes in the splenium on diffusionweighted imaging (DWI) after repeated seizures. METHODS Patients reported in this study were evaluated by using conventional approaches for possible epilepsy surgery. MRI studies were obtained by using protocols that we have optimized for the evaluation of patients with suspected focal epilepsy. All patients were studied on a GE Signa or Siemens Sonata 1.5-Tesla scanner. The standard epilepsy Q1 imaging protocol includes full diffusion tensor imaging [repetition time (ms)/echo time (ms), 6,000/118; field of view (FOV), 40 × 20 cm; matrix, 256 × 256; b value, 0 and 1,000 s/mm 2 ; number of signals acquired, three; gradient directions, six]. Our diffusion sequence automat

When imaging patients with headaches, the goals are: (1) to rule out a more ominous etiology for their headaches and (2) to assess the degree of hemodynamic and parenchymal involvement when atypical or complicated migraine is suspected. The standard images allow other etiologies, such as mass lesions, to be excluded and an MR venogram can rule out venous sinus thrombosis. Contrast may be helpful in differentiating multiple small metastases, demylinating lesions with inflammatory components, and subcortical infarcts from the nonspecific foci of increased T2 associated with migraines that do not enhance. Perfusion-weighted imaging allows detection assessment of hemodynamic compromise. Diffusion-weighted imaging, in combination with the standard MR images, allows assessment of parenchymal involvement. This unit contains a basic protocol which can be used for the evaluation of patients as well as an alternative protocol for the assessment of cerebral perfusion in patients with visual auras.

When imaging patients for vasculitis, the goals are: (1) to determine if there is evidence of acute or subacute cerebral injury and (2) to assess the contour of the major intracranial arteries. An additional but still experimental goal is (3) to determine if there are areas of altered perfusion that suggest active small vessel disease. Standard MR images and diffusion-weighted imaging are used to detect and determine the age of parenchymal lesions. The 3-D TOF MRA helps evaluate the large and medium vessels. Perfusion-weighted imaging may detect regions of altered relative blood flow and blood volume. This unit contains a basic protocol for the evaluation of stable patients as well as an alternative protocol for unstable patients.

Imaging goals for intracranial cerebral vascular disease are (1) to assess the degree of parenchymal injury and identify intraparenchymal hemorrhage; (2) to determine if there are areas of altered perfusion that may be at risk for future injury; and (3) to assess the intracranial arteries (patency as well as direction of flow). This unit describes a Basic Protocol that can be used to evaluate stable patients with acute, subacute, or chronic cerebrovascular symptoms. An Alternate Protocol is also given for cases of hyperacute strokes or cerebrovascular symptoms in an unstable patient.