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Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder of γ-aminobutyrate (GABA) catabolism. Cerebral waste clearance along glymphatic perivascular spaces depends on aquaporin 4 (AQP4) water channels, the function of which was shown to be influenced by GABA. Sleep disturbances are associated independently with SSADHD and glymphatic dysfunction. This study aimed to determine whether indices of the hyperGABAergic state characteristic of SSADHD coincide with glymphatic dysfunction and sleep disturbances and to explicate the modulatory effect that GABA may have on the glymphatic system. The study included 42 individuals (21 with SSADHD; 21 healthy controls) who underwent brain MRIs and magnetic resonance spectroscopy (MRS) for assessment of glymphatic dysfunction and cortical GABA, plasma GABA measurements, and circadian clock gene expression. The SSADHD subjects responded to an additional Children's Sleep Habits Questionnaire (CSHQ). Compared with the control group, SSADHD subjects did not differ in sex and age but had a higher severity of enlarged perivascular spaces in the centrum semiovale (p < 0.001), basal ganglia (p = 0.01), and midbrain (p = 0.001), as well as a higher MRS-derived GABA/NAA peak (p < 0.001). Within the SSADHD group, the severity of glymphatic dysfunction was specific for a lower MRS-derived GABA/NAA (p = 0.04) and lower plasma GABA (p = 0.004). Additionally, the degree of their glymphatic dysfunction correlated with the CSHQ-estimated sleep disturbances scores (R = 5.18, p = 0.03). In the control group, EPVS burden did not correlate with age or cerebral and plasma GABA values. The modulatory effect that GABA may exert on the glymphatic system has therapeutic implications for sleep-related disorders and neurodegenerative conditions associated with glymphatic dysfunction., (© 2023 European Sleep Research Society.)

Background: A lack of in utero imaging data hampers our understanding of the connections in the human fetal brain. Generalizing observations from postmortem subjects and premature newborns is inaccurate due to technical and biological differences., Purpose: To evaluate changes in fetal brain structural connectivity between 23 and 35 weeks postconceptional age using a spatiotemporal atlas of diffusion tensor imaging (DTI)., Study Type: Retrospective., Population: Publicly available diffusion atlases, based on 60 healthy women (age 18-45 years) with normal prenatal care, from 23 and 35 weeks of gestation., Field Strength/sequence: 3.0 Tesla/DTI acquired with diffusion-weighted echo planar imaging (EPI)., Assessment: We performed whole-brain fiber tractography from DTI images. The cortical plate of each diffusion atlas was segmented and parcellated into 78 regions derived from the Edinburgh Neonatal Atlas (ENA33). Connectivity matrices were computed, representing normalized fiber connections between nodes. We examined the relationship between global efficiency (GE), local efficiency (LE), small-worldness (SW), nodal efficiency (NE), and betweenness centrality (BC) with gestational age (GA) and with laterality., Statistical Tests: Linear regression was used to analyze changes in GE, LE, NE, and BC throughout gestation, and to assess changes in laterality. The t-tests were used to assess SW. P-values were corrected using Holm-Bonferroni method. A corrected P-value <0.05 was considered statistically significant., Results: Network analysis revealed a significant weekly increase in GE (5.83%/week, 95% CI 4.32-7.37), LE (5.43%/week, 95% CI 3.63-7.25), and presence of SW across GA. No significant hemisphere differences were found in GE (P = 0.971) or LE (P = 0.458). Increasing GA was significantly associated with increasing NE in 41 nodes, increasing BC in 3 nodes, and decreasing BC in 2 nodes., Data Conclusion: Extensive network development and refinement occur in the second and third trimesters, marked by a rapid increase in global integration and local segregation., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Diffusion magnetic resonance imaging (dMRI) is pivotal for probing the microstructure of the rapidly-developing fetal brain. However, fetal motion during scans and its interaction with magnetic field inhomogeneities result in artifacts and data scattering across spatial and angular domains. The effects of those artifacts are more pronounced in high-angular resolution fetal dMRI, where signal-to-noise ratio is very low. Those effects lead to biased estimates and compromise the consistency and reliability of dMRI analysis. This work presents HAITCH, the first and the only publicly available tool to correct and reconstruct multi-shell high-angular resolution fetal dMRI data. HAITCH offers several technical advances that include a blip-reversed dual-echo acquisition for dynamic distortion correction, advanced motion correction for model-free and robust reconstruction, optimized multi-shell design for enhanced information capture and increased tolerance to motion, and outlier detection for improved reconstruction fidelity. The framework is open-source, flexible, and can be used to process any type of fetal dMRI data including single-echo or single-shell acquisitions, but is most effective when used with multi-shell multi-echo fetal dMRI data that cannot be processed with any of the existing tools. Validation experiments on real fetal dMRI scans demonstrate significant improvements and accurate correction across diverse fetal ages and motion levels. HAITCH successfully removes artifacts and reconstructs high-fidelity fetal dMRI data suitable for advanced diffusion modeling, including fiber orientation distribution function estimation. These advancements pave the way for more reliable analysis of the fetal brain microstructure and tractography under challenging imaging conditions.

Objectives: The T1-weighted GRE (gradient recalled echo) sequence with the Dixon technique for water/fat separation is an essential component of abdominal MRI (magnetic resonance imaging), useful in detecting tumors and characterizing hemorrhage/fat content. Unfortunately, the current implementation of this sequence suffers from several problems: (1) low resolution to maintain high pixel bandwidth and minimize chemical shift; (2) image blurring due to respiratory motion; (3) water/fat swapping due to the natural ambiguity between fat and water peaks; and (4) off-resonance fat blurring due to the multipeak nature of the fat spectrum. The goal of this study was to evaluate the image quality of water/fat separation using a high-resolution 3-point Dixon golden angle radial acquisition with retrospective motion compensation and multipeak fat modeling in children undergoing abdominal MRI., Materials and Methods: Twenty-two pediatric patients (4.2 ± 2.3 years) underwent abdominal MRI on a 3 T scanner with routine abdominal protocol and with a 3-point Dixon radial-VIBE (volumetric interpolated breath-hold examination) sequence. Field maps were calculated using 3D graph-cut optimization followed by fat and water calculation from k-space data by iteratively solving an optimization problem. A 6-peak fat model was used to model chemical shifts in k-space. Residual respiratory motion was corrected through soft-gating by weighting each projection based on the estimated respiratory motion from the center of the k-space. Reconstructed images were reviewed by 3 pediatric radiologists on a PACS (picture archiving and communication systems) workstation. Subjective image quality and water/fat swapping artifact were scored by each pediatric radiologist using a 5-point Likert scale. The VoL (variance of Laplacian) of the reconstructed images was used to objectively quantify image sharpness., Results: Based on the overall Likert scores, the images generated using the described method were significantly superior to those reconstructed by the conventional 2-point Dixon technique (P < 0.05). Water/fat swapping artifact was observed in 14 of 22 patients using 2-point Dixon, and this artifact was not present when using the proposed method. Image sharpness was significantly improved using the proposed framework., Conclusions: In smaller patients, a high-quality water/fat separation with sharp visualization of fine details is critical for diagnostic accuracy. High-resolution golden angle radial-VIBE 3-point Dixon acquisition with 6-peak fat model and soft-gated motion correction offers improved image quality at the expense of an additional ~1-minute acquisition time. Thus, this technique offers the potential to replace the conventional 2-point Dixon technique., Competing Interests: Conflicts of interest and sources of funding: This research was supported in part by NIH grants S10 OD0250111 and R01 EB019483, and by the Department of Radiology at Boston Children's Hospital., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Accurately measuring renal function is crucial for pediatric patients with kidney conditions. Traditional methods have limitations, but dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a safe and efficient approach for detailed anatomical evaluation and renal function assessment. However, motion artifacts during DCE-MRI can degrade image quality and introduce misalignments, leading to unreliable results. This study introduces a motion-compensated reconstruction technique for DCE-MRI data acquired using golden-angle radial sampling. Our proposed method achieves three key objectives: (1) identifying and removing corrupted data (outliers) using a Gaussian process model fitting with a k -space center navigator, (2) efficiently clustering the data into motion phases and performing interphase registration, and (3) utilizing a novel formulation of motion-compensated radial reconstruction. We applied the proposed motion correction (MoCo) method to DCE-MRI data affected by varying degrees of motion, including both respiratory and bulk motion. We compared the outcomes with those obtained from the conventional radial reconstruction. Our evaluation encompassed assessing the quality of images, concentration curves, and tracer kinetic model fitting, and estimating renal function. The proposed MoCo reconstruction improved the temporal signal-to-noise ratio for all subjects, with a 21.8% increase on average, while total variation values of the aorta, right, and left kidney concentration were improved for each subject, with 32.5%, 41.3%, and 42.9% increases on average, respectively. Furthermore, evaluation of tracer kinetic model fitting indicated that the median standard deviation of the estimated filtration rate ( σ F T ), mean normalized root-mean-squared error (nRMSE), and chi-square goodness-of-fit of tracer kinetic model fit were decreased from 0.10 to 0.04, 0.27 to 0.24, and, 0.43 to 0.27, respectively. The proposed MoCo technique enabled more reliable renal function assessment and improved image quality for detailed anatomical evaluation in the case of bulk and respiratory motion during the acquisition of DCE-MRI., (© 2024 John Wiley & Sons Ltd.)

Purpose: To develop a self-navigated motion compensation strategy for 3D radial MRI that can compensate for continuous head motion by measuring rigid body motion parameters with high temporal resolution from the central k-space acquisition point (self-encoded FID navigator) in each radial spoke., Methods: A forward model was created from low-resolution calibration data to simulate the effect of relative motion between the coil sensitivity profiles and the underlying object on the self-encoded FID navigator signal. Trajectory deviations were included in the model as low spatial-order field variations. Three volunteers were imaged at 3 T using a modified 3D gradient-echo sequence acquired with a Kooshball trajectory while performing abrupt and continuous head motion. Rigid body-motion parameters were estimated from the central k-space signal of each spoke using a least-squares fitting algorithm. The accuracy of self-navigated motion parameters was assessed relative to an established external tracking system. Quantitative image quality metrics were computed for images with and without retrospective correction using external and self-navigated motion measurements., Results: Self-encoded FID navigators achieved mean absolute errors of 0.69 ± 0.82 mm and 0.73 ± 0.87° relative to external tracking for maximum motion amplitudes of 12 mm and 10°. Retrospective correction of the 3D radial data resulted in substantially improved image quality for both abrupt and continuous motion paradigms, comparable to external tracking results., Conclusions: Accurate rigid body motion parameters can be rapidly obtained from self-encoded FID navigator signals in 3D radial MRI to continuously correct for head movements. This approach is suitable for robust neuroanatomical imaging in subjects that exhibit patterns of large and frequent motion., (© 2023 International Society for Magnetic Resonance in Medicine.)

We utilized motion-corrected diffusion tensor imaging (DTI) to evaluate microstructural changes in healthy fetal brains during the late second and third trimesters. Data were derived from fetal magnetic resonance imaging scans conducted as part of a prospective study spanning from 2013 March to 2019 May. The study included 44 fetuses between the gestational ages (GAs) of 23 and 36 weeks. We reconstructed fetal brain DTI using a motion-tracked slice-to-volume registration framework. Images were segmented into 14 regions of interest (ROIs) through label propagation using a fetal DTI atlas, with expert refinement. Statistical analysis involved assessing changes in fractional anisotropy (FA) and mean diffusivity (MD) throughout gestation using mixed-effects models, and identifying points of change in trajectory for ROIs with nonlinear trends. Results showed significant GA-related changes in FA and MD in all ROIs except in the thalamus' FA and corpus callosum's MD. Hemispheric asymmetries were found in the FA of the periventricular white matter (pvWM), intermediate zone, and subplate and in the MD of the ganglionic eminence and pvWM. This study provides valuable insight into the normal patterns of development of MD and FA in the fetal brain. These changes are closely linked with cytoarchitectonic changes and display indications of early functional specialization., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We introduce a generative model for synthesis of large scale 3D datasets for quantitative parameter mapping of myelin water fraction (MWF). Our model combines a MR physics signal decay model with an accurate probabilistic multi-component parametric T2 model. We synthetically generate a wide variety of high quality signals and corresponding parameters from a wide range of naturally occurring prior parameter values. To capture spatial variation, the generative signal decay model is combined with a generative spatial model conditioned on generic tissue segmentations. Synthesized 3D datasets can be used to train any convolutional neural network (CNN) based architecture for MWF estimation. Our source code is available at: https://github.com/quin-med-harvard-edu/synthmap Reduction of acquisition time at the expense of lower SNR, as well as accuracy and repeatability of MWF estimation techniques, are key factors that affect the adoption of MWF mapping in clinical practice. We demonstrate that the synthetically trained CNN provides superior accuracy over the competing methods under the constraints of naturally occurring noise levels as well as on the synthetically generated images at low SNR levels. Normalized root mean squared error (nRMSE) is less than 7% on synthetic data, which is significantly lower than competing methods. Additionally, the proposed method yields a coefficient of variation (CoV) that is at least 4x better than the competing method on intra-session test-retest reference dataset., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessively inherited metabolic disorder of γ-aminobutyric acid catabolism manifested by intellectual disability, expressive aphasia, movement disorders, psychiatric ailments and epilepsy. Subjects with succinic semialdehyde dehydrogenase deficiency are characterized by elevated γ-aminobutyric acid and related metabolites, such as γ-guanidinobutyric acid, and an age-dependent downregulation of cerebral γ-aminobutyric acid receptors. These findings indicate impaired γ-aminobutyric acid and γ-aminobutyric acid sub-type A (GABA A ) receptor signalling as major factors underlying the pathophysiology of this neurometabolic disorder. We studied the cortical oscillation patterns and their relationship with γ-aminobutyric acid metabolism in 18 children affected by this condition and 10 healthy controls. Using high-density EEG, we recorded somatosensory cortical responses and resting-state activity. Using electrical source imaging, we estimated the relative power changes (compared with baseline) in both stimulus-evoked and stimulus-induced responses for physiologically relevant frequency bands and resting-state power. Stimulus-evoked oscillations are phase locked to the stimulus, whereas induced oscillations are not. Power changes for both evoked and induced responses as well as resting-state power were correlated with plasma γ-aminobutyric acid and γ-guanidinobutyric acid concentrations and with cortical γ-aminobutyric acid measured by proton magnetic resonance spectroscopy. Plasma γ-aminobutyric acid, γ-guanidinobutyric acid and cortical γ-aminobutyric acid were higher in patients than in controls ( P < 0.001 for both). Beta and gamma relative power were suppressed for evoked responses in patients versus controls ( P < 0.01). No group differences were observed for induced activity ( P > 0.05). The mean gamma frequency of evoked responses was lower in patients versus controls ( P = 0.002). Resting-state activity was suppressed in patients for theta ( P = 0.011) and gamma ( P < 0.001) bands. Evoked power changes were inversely correlated with plasma γ-aminobutyric acid and with γ-guanidinobutyric acid for beta ( P < 0.001) and gamma ( P < 0.001) bands. Similar relationships were observed between the evoked power changes and cortical γ-aminobutyric acid for all tested areas in the beta band ( P < 0.001) and for the posterior cingulate gyrus in the gamma band ( P < 0.001). We also observed a negative correlation between resting-state activity and plasma γ-aminobutyric acid and γ-guanidinobutyric acid for theta ( P < 0.001; P = 0.003), alpha ( P = 0.003; P = 0.02) and gamma ( P = 0.02; P = 0.01) bands. Our findings indicate that increased γ-aminobutyric acid concentration is associated with reduced sensory-evoked beta and gamma activity and impaired neuronal synchronization in patients with succinic semialdehyde dehydrogenase deficiency. This further elucidates the pathophysiology of this neurometabolic disorder and serves as a potential biomarker for therapeutic trials., Competing Interests: The authors report no competing interests., (Published by Oxford University Press on behalf of the Guarantors of Brain 2023.)

Quantitative diffusion weighted MRI in the abdomen provides important markers of disease, however significant limitations exist for its accurate computation. One such limitation is the low signal-to-noise ratio, particularly at high diffusion b-values. To address this, multiple diffusion directional images can be collected at each b-value and geometrically averaged, which invariably leads to longer scan time, blurring due to motion and other artifacts. We propose a novel parameter estimation technique based on self supervised diffusion denoising probabilistic model that can effectively denoise diffusion weighted images and work on single diffusion gradient direction images. Our source code is made available at https://github.com/quin-med-harvard-edu/ssDDPM.

Background and Purpose: To perform a volumetric evaluation of the brain in fetuses with right or left congenital diaphragmatic hernia (CDH), and to compare brain growth trajectories to normal fetuses., Methods: We identified fetal MRIs performed between 2015 and 2020 in fetuses with a diagnosis of CDH. Gestational age (GA) range was 19-40 weeks. Control subjects consisted of normally developing fetuses between 19 and 40 weeks recruited for a separate prospective study. All images were acquired at 3 Tesla and were processed with retrospective motion correction and slice-to-volume reconstruction to generate super-resolution 3-dimensional volumes. These volumes were registered to a common atlas space and segmented in 29 anatomic parcellations., Results: A total of 174 fetal MRIs in 149 fetuses were analyzed (99 controls [mean GA: 29.2 ± 5.2 weeks], 34 fetuses left-sided CDH [mean GA: 28.4 ± 5.3 weeks], and 16 fetuses right-sided CDH [mean GA: 27 ± 5.4 weeks]). In fetuses with left-sided CDH, brain parenchymal volume was -8.0% (95% confidence interval [CI] [-13.1, -2.5]; p = .005) lower than normal controls. Differences ranged from -11.4% (95% CI [-18, -4.3]; p < .001) in the corpus callosum to -4.6% (95% CI [-8.9, -0.1]; p = .044) in the hippocampus. In fetuses with right-sided CDH, brain parenchymal volume was -10.1% (95% CI [-16.8, -2.7]; p = .008) lower than controls. Differences ranged from -14.1% (95% CI [-21, -6.5]; p < .001) in the ventricular zone to -5.6% (95% CI [-9.3, -1.8]; p = .025) in the brainstem., Conclusion: Left and right CDH are associated with lower fetal brain volumes., (© 2023 American Society of Neuroimaging.)

Fetal MRI has emerged as a cornerstone of prenatal imaging, helping to establish the correct diagnosis in pregnancies affected by congenital anomalies. In the past decade, 3 T imaging was introduced as an alternative to increase the signal-to-noise ratio (SNR) of the pulse sequences and improve anatomic detail. However, imaging at a higher field strength is not without challenges. Many artifacts that are barely appreciable at 1.5 T are amplified at 3 T. A systematic approach to imaging at 3 T that incorporates appropriate patient positioning, a thoughtful protocol design, and sequence optimization minimizes the impact of these artifacts and allows radiologists to reap the benefits of the increased SNR. The sequences used are the same at both field strengths and include single-shot T2-weighted, balanced steady-state free-precession, three-dimensional T1-weighted spoiled gradient-echo, and echo-planar imaging. Synergistic use of these acquisitions to sample various tissue contrasts and in various planes provides valuable information about fetal anatomy and pathologic conditions. In the authors' experience, fetal imaging at 3 T outperforms imaging at 1.5 T for most indications when performed under optimal circumstances. The authors condense the cumulative experience of fetal imaging specialists and MRI technologists who practice at a large referral center into a guideline covering all major aspects of fetal MRI at 3 T, from patient preparation to image interpretation. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Complex engineered systems are often equipped with suites of sensors and ancillary devices that monitor their performance and maintenance needs. MRI scanners are no different in this regard. Some of the ancillary devices available to support MRI equipment, the ones of particular interest here, have the distinction of actually participating in the image acquisition process itself. Most commonly, such devices are used to monitor physiological motion or variations in the scanner's imaging fields, allowing the imaging and/or reconstruction process to adapt as imaging conditions change. "Classic" examples include electrocardiography (ECG) leads and respiratory bellows to monitor cardiac and respiratory motion, which have been standard equipment in scan rooms since the early days of MRI. Since then, many additional sensors and devices have been proposed to support MRI acquisitions. The main physical properties that they measure may be primarily "mechanical" (eg acceleration, speed, and torque), "acoustic" (sound and ultrasound), "optical" (light and infrared), or "electromagnetic" in nature. A review of these ancillary devices, as currently available in clinical and research settings, is presented here. In our opinion, these devices are not in competition with each other: as long as they provide useful and unique information, do not interfere with each other and are not prohibitively cumbersome to use, they might find their proper place in future suites of sensors. In time, MRI acquisitions will likely include a plurality of complementary signals. A little like the microbiome that provides genetic diversity to organisms, these devices can provide signal diversity to MRI acquisitions and enrich measurements. Machine-learning (ML) algorithms are well suited at combining diverse input signals toward coherent outputs, and they could make use of all such information toward improved MRI capabilities. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1., (© 2022 International Society for Magnetic Resonance in Medicine.)

This work presents detailed anatomic labels for a spatiotemporal atlas of fetal brain Diffusion Tensor Imaging (DTI) between 23 and 30 weeks of post-conceptional age. Additionally, we examined developmental trajectories in fractional anisotropy (FA) and mean diffusivity (MD) across gestational ages (GA). We performed manual segmentations on a fetal brain DTI atlas. We labeled 14 regions of interest (ROIs): cortical plate (CP), subplate (SP), Intermediate zone-subventricular zone-ventricular zone (IZ/SVZ/VZ), Ganglionic Eminence (GE), anterior and posterior limbs of the internal capsule (ALIC, PLIC), genu (GCC), body (BCC), and splenium (SCC) of the corpus callosum (CC), hippocampus, lentiform Nucleus, thalamus, brainstem, and cerebellum. A series of linear regressions were used to assess GA as a predictor of FA and MD for each ROI. The combination of MD and FA allowed the identification of all ROIs. Increasing GA was significantly associated with decreasing FA in the CP, SP, IZ/SVZ/IZ, GE, ALIC, hippocampus, and BCC (p < .03, for all), and with increasing FA in the PLIC and SCC (p < .002, for both). Increasing GA was significantly associated with increasing MD in the CP, SP, IZ/SVZ/IZ, GE, ALIC, and CC (p < .03, for all). We developed a set of expert-annotated labels for a DTI spatiotemporal atlas of the fetal brain and presented a pilot analysis of developmental changes in cerebral microstructure between 23 and 30 weeks of GA., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Prolonged morphine treatment in infancy is associated with a high incidence of opioid tolerance and dependence, but our knowledge of the long-term consequences of this treatment is sparse. Using a rodent model, we examined the (1) short- and (2) long-term effects of prolonged morphine administration in infancy on body weight and brain volume, and (3) we evaluated if subsequent dosing in adulthood poses an increased brain vulnerability., Methods: Newborn rats received subcutaneous injections of either morphine or equal volume of saline twice daily for the first two weeks of life. In adulthood, animals received an additional two weeks of saline or morphine injections before undergoing structural brain MRI. After completion of treatment, structural T2-weigthed MRI images were acquired on a 7 T preclinical scanner (Bruker) using a RARE FSE sequence. Total and regional brain volumes were manually extracted from the MRI images using ITK-SNAP (v.3.6). Regions of interest included the brainstem, the cerebellum, as well as the forebrain and its components: the cerebral cortex, hippocampus, and deep gray matter (including basal ganglia, thalamus, hypothalamus, ventral tegmental area). Absolute (cm 3 ) and normalized (as % total brain volume) values were compared using a one-way ANOVA with Tukey HSD post-hoc test., Results: Prolonged morphine administration in infancy was associated with lower body weight and globally smaller brain volumes, which was not different between the sexes. In adulthood, females had lower body weights than males, but no difference was observed in brain volumes between treatment groups. Our results are suggestive of no long-term effect of prolonged morphine treatment in infancy with respect to body weight and brain size in either sex. Interestingly, prolonged morphine administration in adulthood was associated with smaller brain volumes that differed by sex only in case of previous exposure to morphine in infancy. Specifically, we report significantly smaller total brain volume of female rats on account of decreased volumes of forebrain and cortex., Conclusions: Our study provides insight into the short- and long-term consequences of prolonged morphine administration in an infant rat model and suggests brain vulnerability to subsequent exposure in adulthood that might differ with sex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Taylor, Cheng, Hodkinson, Afacan, Zurakowski and Bajic.)

Purpose: Abdominal MRI scans may require breath-holding to prevent image quality degradation, which can be challenging for patients, especially children. In this study, we evaluate whether FID navigators can be used to measure and correct for motion prospectively, in real-time., Methods: FID navigators were inserted into a 3D radial sequence with stack-of-stars sampling. MRI experiments were conducted on 6 healthy volunteers. A calibration scan was first acquired to create a linear motion model that estimates the kidney displacement due to respiration from the FID navigator signal. This model was then applied to predict and prospectively correct for motion in real time during deep and continuous deep breathing scans. Resultant images acquired with the proposed technique were compared with those acquired without motion correction. Dice scores were calculated between inhale/exhale motion states. Furthermore, images acquired using the proposed technique were compared with images from extra-dimensional golden-angle radial sparse parallel, a retrospective motion state binning technique., Results: Images reconstructed for each motion state show that the kidneys' position could be accurately tracked and corrected with the proposed method. The mean of Dice scores computed between the motion states were improved from 0.93 to 0.96 using the proposed technique. Depiction of the kidneys was improved in the combined images of all motion states. Comparing results of the proposed technique and extra-dimensional golden-angle radial sparse parallel, high-quality images can be reconstructed from a fraction of spokes using the proposed method., Conclusion: The proposed technique reduces blurriness and motion artifacts in kidney imaging by prospectively correcting their position both in-plane and through-slice., (© 2022 International Society for Magnetic Resonance in Medicine.)

Background: Although randomized controlled trials comparing hip arthroscopy with physical therapy for the treatment of femoroacetabular impingement (FAI) syndrome have emerged, no studies have investigated potential moderators or mediators of change in hip-related quality of life., Purpose: To explore potential moderators, mediators, and prognostic indicators of the effect of hip arthroscopy and physical therapy on change in 33-item international Hip Outcome Tool (iHOT-33) score for FAI syndrome., Study Design: Cohort study; Level of evidence, 2., Methods: Overall, 99 participants were recruited from the clinics of orthopaedic surgeons and randomly allocated to treatment with hip arthroscopy or physical therapy. Change in iHOT-33 score from baseline to 12 months was the dependent outcome for analyses of moderators, mediators, and prognostic indicators. Variables investigated as potential moderators/prognostic indicators were demographic variables, symptom duration, alpha angle, lateral center-edge angle (LCEA), Hip Osteoarthritis MRI Scoring System (HOAMS) for selected magnetic resonance imaging (MRI) features, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) score. Potential mediators investigated were change in chosen bony morphology measures, HOAMS, and dGEMRIC score from baseline to 12 months. For hip arthroscopy, intraoperative procedures performed (femoral ostectomy ± acetabular ostectomy ± labral repair ± ligamentum teres debridement) and quality of surgery graded by a blinded surgical review panel were investigated for potential association with iHOT-33 change. For physical therapy, fidelity to the physical therapy program was investigated for potential association with iHOT-33 change., Results: A total of 81 participants were included in the final moderator/prognostic indicator analysis and 85 participants in the final mediator analysis after exclusion of those with missing data. No significant moderators or mediators of change in iHOT-33 score from baseline to 12 months were identified. Patients with smaller baseline LCEA (β = -0.82; P = .034), access to private health care (β = 12.91; P = .013), and worse baseline iHOT-33 score (β = -0.48; P < .001) had greater iHOT-33 improvement from baseline to 12 months, irrespective of treatment allocation, and thus were prognostic indicators of treatment response. Unsatisfactory treatment fidelity was associated with worse treatment response (β = -24.27; P = .013) for physical therapy. The quality of surgery and procedures performed were not associated with iHOT-33 change for hip arthroscopy ( P = .460-.665 and P = .096-.824, respectively)., Conclusion: No moderators or mediators of change in hip-related quality of life were identified for treatment of FAI syndrome with hip arthroscopy or physical therapy in these exploratory analyses. Patients who accessed the Australian private health care system, had smaller LCEAs, and had worse baseline iHOT-33 scores, experienced greater iHOT-33 improvement, irrespective of treatment allocation.

Purpose: To implement a method for real-time field control using rapid FID navigator (FIDnav) measurements and evaluate the efficacy of the proposed approach for mitigating dynamic field perturbations and improving INLINEMATH -weighted image quality., Methods: FIDnavs were embedded in a gradient echo sequence and a subject-specific linear calibration model was generated on the scanner to facilitate rapid shim updates in response to measured FIDnav signals. To confirm the accuracy of FID-navigated field updates, phantom and volunteer scans were performed with online updates of the scanner B 0 shim settings. To evaluate improvement in INLINEMATH -weighted image quality with real-time shimming, 10 volunteers were scanned at 3T while performing deep-breathing and nose-touching tasks designed to modulate the B 0 field. Quantitative image quality metrics were compared with and without FID-navigated field control. An additional volunteer was scanned at 7T to evaluate performance at ultra-high field., Results: Applying measured FIDnav shim updates successfully compensated for applied global and linear field offsets in phantoms and across all volunteers. FID-navigated real-time shimming led to a substantial reduction in field fluctuations and a consequent improvement in INLINEMATH -weighted image quality in volunteers performing deep-breathing and nose-touching tasks, with 7.57% ± 6.01% and 8.21% ± 10.90% improvement in peak SNR and structural similarity, respectively., Conclusion: FIDnavs facilitate rapid measurement and application of field coefficients for slice-wise B 0 shimming. The proposed approach can successfully counteract spatiotemporal field perturbations and substantially improves INLINEMATH -weighted image quality, which is important for a variety of clinical and research applications, particularly at ultra-high field., (© 2022 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: Pediatric-onset multiple sclerosis (POMS) shows earlier axonal involvement and greater axonal loss than in adults. We aim to characterize the white matter (WM) microstructural changes in POMS using a diffusion compartment imaging (DCI) model and compare it to standard diffusion tensor imaging (DTI)., Methods: Eleven patients (2 males, mean age 18.8 ± 3.9 years) with a diagnosis of relapsing and remitting POMS (mean age at disease onset 13.8 ± 2.9 years, mean duration 5.1 ± 1.9 years) and healthy controls (8 males, mean age 26.4 ± 6.5 years) were recruited and imaged at 3 T. A 90-gradient set Cube and Sphere acquisition and a novel DCI model known as DIstribution of Anisotropic MicrOstructural eNvironments with Diffusion-weighted imaging (DIAMOND) were used to calculate a single anisotropic compartment, an isotropic compartment, and a free diffusion compartment. Lesions and contralateral normal-appearing white matter (NAWM) in patients and whole brain WM for controls were labeled., Results: Eleven patients and 11 controls were recruited. When comparing lesions and contralateral NAWM in patients using DCI, compartmental axial diffusivity, radial diffusivity (cRD), and mean diffusivity (cMD) were higher in lesions. Conversely, compartmental fractional anisotropy (cFA) and heterogeneity index were lower in lesions. An analysis of DTI equivalents showed the same trends. In whole-brain NAWM of patients compared to controls, cRD and cMD were higher and cFA was lower in patients., Conclusion: Lesions in POMS can be accurately characterized by a DCI model. Incipient changes in NAWM seen in DCI may not be readily observable by DTI., (© 2022 American Society of Neuroimaging.)

The interpretation and analysis of Magnetic resonance imaging (MRI) benefit from high spatial resolution. Unfortunately, direct acquisition of high spatial resolution MRI is time-consuming and costly, which increases the potential for motion artifact, and suffers from reduced signal-to-noise ratio (SNR). Super-resolution reconstruction (SRR) is one of the most widely used methods in MRI since it allows for the trade-off between high spatial resolution, high SNR, and reduced scan times. Deep learning has emerged for improved SRR as compared to conventional methods. However, current deep learning-based SRR methods require large-scale training datasets of high-resolution images, which are practically difficult to obtain at a suitable SNR. We sought to develop a methodology that allows for dataset-free deep learning-based SRR, through which to construct images with higher spatial resolution and of higher SNR than can be practically obtained by direct Fourier encoding. We developed a dataset-free learning method that leverages a generative neural network trained for each specific scan or set of scans, which in turn, allows for SRR tailored to the individual patient. With the SRR from three short duration scans, we achieved high quality brain MRI at an isotropic spatial resolution of 0.125 cubic mm with six minutes of imaging time for T2 contrast and an average increase of 7.2 dB (34.2%) in SNR to these short duration scans. Motion compensation was achieved by aligning the three short duration scans together. We assessed our technique on simulated MRI data and clinical data acquired from 15 subjects. Extensive experimental results demonstrate that our approach achieved superior results to state-of-the-art methods, while in parallel, performed at reduced cost as scans delivered with direct high-resolution acquisition.

Background Tools in image reconstruction, motion correction, and segmentation have enabled the accurate volumetric characterization of fetal brain growth at MRI. Purpose To evaluate the volumetric growth of intracranial structures in healthy fetuses, accounting for gestational age (GA), sex, and laterality with use of a spatiotemporal MRI atlas of fetal brain development. Materials and Methods T2-weighted 3.0-T half-Fourier acquired single-shot turbo spin-echo sequence MRI was performed in healthy fetuses from prospectively recruited pregnant volunteers from March 2013 to May 2019. A previously validated section-to-volume reconstruction algorithm was used to generate intensity-normalized superresolution three-dimensional volumes that were registered to a fetal brain MRI atlas with 28 anatomic regions of interest. Atlas-based segmentation was performed and manually refined. Labels included the bilateral hippocampus, amygdala, caudate nucleus, lentiform nucleus, thalamus, lateral ventricle, cerebellum, cortical plate, hemispheric white matter, internal capsule, ganglionic eminence, ventricular zone, corpus callosum, brainstem, hippocampal commissure, and extra-axial cerebrospinal fluid. For fetuses younger than 31 weeks of GA, the subplate and intermediate zones were delineated. A linear regression analysis was used to determine weekly age-related change adjusted for sex and laterality. Results The final analytic sample consisted of 122 MRI scans in 98 fetuses (mean GA, 29 weeks ± 5 [range, 20-38 weeks]). All structures had significant volume growth with increasing GA ( P < .001). Weekly age-related change for individual structures in the brain parenchyma ranged from 2.0% (95% CI: 0.9, 3.1; P < .001) in the hippocampal commissure to 19.4% (95% CI: 18.7, 20.1; P < .001) in the cerebellum. The largest sex-related differences were 22.1% higher volume in male fetuses for the lateral ventricles (95% CI: 10.9, 34.4; P < .001). There was rightward volumetric asymmetry of 15.6% for the hippocampus (95% CI: 14.2, 17.2; P < .001) and leftward volumetric asymmetry of 8.1% for the lateral ventricles (95% CI: 3.7, 12.2; P < .001). Conclusion With use of a spatiotemporal MRI atlas, volumetric growth of the fetal brain showed complex trajectories dependent on structure, gestational age, sex, and laterality. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Rollins in this issue.

Purpose: To assess the robustness and repeatability of intravoxel incoherent motion model (IVIM) parameter estimation for the diffusion-weighted MRI in the abdominal organs under the constraints of noisy diffusion signal using a novel neural network method., Methods: Clinically acquired abdominal scans of Crohn's disease patients were retrospectively analyzed with regions segmented in the kidney cortex, spleen, liver, and bowel. A novel IVIM parameter fitting method based on the principle of a physics guided self-supervised convolutional neural network that does not require reference parameter estimates for training was compared to a conventional non-linear least squares (NNLS) algorithm, and a voxelwise trained artificial neural network (ANN)., Results: Results showed substantial increase in parameter robustness to the noise corrupted signal. In an intra-session repeatability experiment, the proposed method showed reduced coefficient of variation (CoV) over multiple acquisitions in comparison to conventional NLLS method and comparable performance to ANN. The use of D and f estimates from the proposed method led to the smallest misclassification error in linear discriminant analysis for characterization between normal and abnormal Crohn's disease bowel tissue. The fitting of D ∗ parameter remains to be challenging., Conclusion: The proposed method yields robust estimates of D and f IVIM parameters under the constraints of noisy diffusion signal. This indicates a potential for the use of the proposed method in conjunction with accelerated DW-MRI acquisition strategies, which would typically result in lower signal to noise ratio., (© 2021 International Society for Magnetic Resonance in Medicine.)

Kidney DCE-MRI aims at both qualitative assessment of kidney anatomy and quantitative assessment of kidney function by estimating the tracer kinetic (TK) model parameters. Accurate estimation of TK model parameters requires an accurate measurement of the arterial input function (AIF) with high temporal resolution. Accelerated imaging is used to achieve high temporal resolution, which yields under-sampling artifacts in the reconstructed images. Compressed sensing (CS) methods offer a variety of reconstruction options. Most commonly, sparsity of temporal differences is encouraged for regularization to reduce artifacts. Increasing regularization in CS methods removes the ambient artifacts but also over-smooths the signal temporally which reduces the parameter estimation accuracy. In this work, we propose a single image trained deep neural network to reduce MRI under-sampling artifacts without reducing the accuracy of functional imaging markers. Instead of regularizing with a penalty term in optimization, we promote regularization by generating images from a lower dimensional representation. In this manuscript we motivate and explain the lower dimensional input design. We compare our approach to CS reconstructions with multiple regularization weights. Proposed approach results in kidney biomarkers that are highly correlated with the ground truth markers estimated using the CS reconstruction which was optimized for functional analysis. At the same time, the proposed approach reduces the artifacts in the reconstructed images.

Functional MRI (fMRI) is widely used to study the functional organization of normal and pathological brains. However, the fMRI signal may be contaminated by subject motion artifacts that are only partially mitigated by motion correction strategies. These artifacts lead to distance-dependent biases in the inferred signal correlations. To mitigate these spurious effects, motion-corrupted volumes are censored from fMRI time series. Censoring can result in discontinuities in the fMRI signal, which may lead to substantial alterations in functional connectivity analysis. We propose a new approach to recover the missing entries from censoring based on structured low rank matrix completion. We formulated the artifact-reduction problem as the recovery of a super-resolved matrix from unprocessed fMRI measurements. We enforced a low rank prior on a large structured matrix, formed from the samples of the time series, to recover the missing entries. The recovered time series, in addition to being motion compensated, are also slice-time corrected at a fine temporal resolution. To achieve a fast and memory-efficient solution for our proposed optimization problem, we employed a variable splitting strategy. We validated the algorithm with simulations, data acquired under different motion conditions, and datasets from the ABCD study. Functional connectivity analysis showed that the proposed reconstruction resulted in connectivity matrices with lower errors in pair-wise correlation than non-censored and censored time series based on a standard processing pipeline. In addition, seed-based correlation analyses showed improved delineation of the default mode network. These demonstrate that the method can effectively reduce the adverse effects of motion in fMRI analysis.

Background and Purpose: Super-resolutionreconstruction (SRR) can be used to reconstruct 3-dimensional (3D) high-resolution (HR) volume from several 2-dimensional (2D) low-resolution (LR) stacks of MRI slices. The purpose is to compare lengthy 2D T2-weighted HR image acquisition of neonatal subjects with 3D SRR from several LR stacks in terms of image quality for clinical and morphometric assessments., Methods: LR brain images were acquired from neonatal subjects to reconstruct isotropic 3D HR volumes by using SRR algorithm. Quality assessments were done by an experienced pediatric radiologist using scoring criteria adapted to newborn anatomical landmarks. The Wilcoxon signed-rank test was used to compare scoring results between HR and SRR images. For quantitative assessments, morphology-based segmentation was performed on both HR and SRR images and Dice coefficients between the results were computed. Additionally, simple linear regression was performed to compare the tissue volumes., Results: No statistical difference was found between HR and SRR structural scores using Wilcoxon signed-rank test (p = .63, Z = .48). Regarding segmentation results, R 2 values for the volumes of gray matter, white matter, cerebrospinal fluid, basal ganglia, cerebellum, and total brain volume including brain stem ranged between .95 and .99. Dice coefficients between the segmented regions from HR and SRR ranged between .83 ± .04 and .96 ± .01., Conclusion: Qualitative and quantitative assessments showed that 3D SRR of several LR images produces images that are of comparable quality to standard 2D HR image acquisition for healthy neonatal imaging without loss of anatomical details with similar edge definition allowing the detection of fine anatomical structures and permitting comparable morphometric measurement., (© 2021 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract-based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super-resolution algorithm and DTI images processed with a motion-tracked slice-to-volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor-to-tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within-tract changes. We found tract-specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within-tract developmental trajectories for the CST, IFOF, and forceps major., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

There is a growing demand for fast, accurate computation of clinical markers to improve renal function and anatomy assessment with a single study. However, conventional techniques have limitations leading to overestimations of kidney function or failure to provide sufficient spatial resolution to target the disease location. In contrast, the computer-aided analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) could generate significant markers, including the glomerular filtration rate (GFR) and time-intensity curves of the cortex and medulla for determining obstruction in the urinary tract. This paper presents a dual-stage fully modular framework for automatic renal compartment segmentation in 4D DCE-MRI volumes. (1) Memory-efficient 3D deep learning is integrated to localise each kidney by harnessing residual convolutional neural networks for improved convergence; segmentation is performed by efficiently learning spatial-temporal information coupled with boundary-preserving fully convolutional dense nets. (2) Renal contextual information is enhanced via non-linear transformation to segment the cortex and medulla. The proposed framework is evaluated on a paediatric dataset containing 60 4D DCE-MRI volumes exhibiting varying conditions affecting kidney function. Our technique outperforms a state-of-the-art approach based on a GrabCut and support vector machine classifier in mean dice similarity (DSC) by 3.8% and demonstrates higher statistical stability with lower standard deviation by 12.4% and 15.7% for cortex and medulla segmentation, respectively.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of γ-aminobutyric acid (GABA) degradation, resulting in elevations of brain GABA and γ-hydroxybutyric acid (GHB). Previous magnetic resonance (MR) spectroscopy studies have shown increased levels of Glx in SSADH deficiency patients. Here in this work, we measure brain GABA in a large cohort of SSADH deficiency patients using advanced MR spectroscopy techniques that allow separation of GABA from overlapping metabolite peaks. We observed significant increases in GABA concentrations in SSADH deficiency patients for all 3 brain regions that were evaluated. Although GABA levels were higher in all 3 regions, each region had different patterns in terms of GABA changes with respect to age. We also report results from structural magnetic resonance imaging (MRI) of the same cohort compared with age-matched controls. We consistently observed signal hyperintensities in globus pallidus and cerebellar dentate nucleus.

Spatial resolution plays a critically important role in MRI for the precise delineation of the imaged tissues. Unfortunately, acquisitions with high spatial resolution require increased imaging time, which increases the potential of subject motion, and suffers from reduced signal-to-noise ratio (SNR). Super-resolution reconstruction (SRR) has recently emerged as a technique that allows for a trade-off between high spatial resolution, high SNR, and short scan duration. Deconvolution-based SRR has recently received significant interest due to the convenience of using the image space. The most critical factor to succeed in deconvolution is the accuracy of the estimated blur kernels that characterize how the image was degraded in the acquisition process. Current methods use handcrafted filters, such as Gaussian filters, to approximate the blur kernels, and have achieved promising SRR results. As the image degradation is complex and varies with different sequences and scanners, handcrafted filters, unfortunately, do not necessarily ensure the success of the deconvolution. We sought to develop a technique that enables accurately estimating blur kernels from the image data itself. We designed a deep architecture that utilizes an adversarial scheme with a generative neural network against its degradation counterparts. This design allows for the SRR tailored to an individual subject, as the training requires the scan-specific data only, i.e., it does not require auxiliary datasets of high-quality images, which are practically challenging to obtain. With this technique, we achieved high-quality brain MRI at an isotropic resolution of 0.125 cubic mm with six minutes of imaging time. Extensive experiments on both simulated low-resolution data and clinical data acquired from ten pediatric patients demonstrated that our approach achieved superior SRR results as compared to state-of-the-art deconvolution-based methods, while in parallel, at substantially reduced imaging time in comparison to direct high-resolution acquisitions.

Background and Purpose: Functional MRI neurofeedback (fMRI-nf) leverages the brain's ability to self-regulate its own activity. However, self-regulation processes engaged during fMRI-nf are incompletely understood. Here, we used matched feedback in an fMRI-nf experimental protocol to investigate whether brain processes recognize true neurofeedback signals., Methods: We implemented an existing fMRI-nf protocol to train lateralized motor activity using a finger-tap task in conjunction with real-time feedback. Twelve healthy, right-handed, adult participants were assigned into age- and sex-matched active and sham study groups. Matched participant pairs received the same visual feedback, based on brain activity of the participant from the active group. We compared group-averaged activation maps before, during, and after neurofeedback, and analyzed changes in lateralized motor activity due to neurofeedback., Results: Active and sham groups demonstrated different brain activation to the same feedback during neurofeedback. In particular, there was higher activation in visual cortex, secondary somatosensory cortex, and right inferior frontal gyrus in the active group compared to the sham group. Conversely, sham participants demonstrated higher activation in anterior cingulate cortex, left frontal pole, and posterior superior temporal gyrus. Despite differing brain activations during neurofeedback, neither group demonstrated significant improvement in lateralized motor activity from pre to postfeedback scan in the same session. We also observed no significant difference between pre and postfeedback activation maps, suggesting that no significant finger-tap related functional reorganization had occurred., Conclusions: These findings suggest that fMRI neurofeedback paradigms that monitor or incorporate activity from regions reported here would provide enhanced efficacy for research investigation and clinical intervention., (© 2021 American Society of Neuroimaging.)

The brain of neonates is small in comparison to adults. Imaging at typical resolutions such as one cubic mm incurs more partial voluming artifacts in a neonate than in an adult. The interpretation and analysis of MRI of the neonatal brain benefit from a reduction in partial volume averaging that can be achieved with high spatial resolution. Unfortunately, direct acquisition of high spatial resolution MRI is slow, which increases the potential for motion artifact, and suffers from reduced signal-to-noise ratio. The purpose of this study is thus that using super-resolution reconstruction in conjunction with fast imaging protocols to construct neonatal brain MRI images at a suitable signal-to-noise ratio and with higher spatial resolution than can be practically obtained by direct Fourier encoding. We achieved high quality brain MRI at a spatial resolution of isotropic 0.4 mm with 6 min of imaging time, using super-resolution reconstruction from three short duration scans with variable directions of slice selection. Motion compensation was achieved by aligning the three short duration scans together. We applied this technique to 20 newborns and assessed the quality of the images we reconstructed. Experiments show that our approach to super-resolution reconstruction achieved considerable improvement in spatial resolution and signal-to-noise ratio, while, in parallel, substantially reduced scan times, as compared to direct high-resolution acquisitions. The experimental results demonstrate that our approach allowed for fast and high-quality neonatal brain MRI for both scientific research and clinical studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sui, Afacan, Gholipour and Warfield.)

Accurate, quantitative segmentation of anatomical structures in radiological scans, such as Magnetic Resonance Imaging (MRI) and Computer Tomography (CT), can produce significant biomarkers and can be integrated into computer-aided assisted diagnosis (CADx) systems to support the interpretation of medical images from multi-protocol scanners. However, there are serious challenges towards developing robust automated segmentation techniques, including high variations in anatomical structure and size, the presence of edge-based artefacts, and heavy un-controlled breathing that can produce blurred motion-based artefacts. This paper presents a novel computing approach for automatic organ and muscle segmentation in medical images from multiple modalities by harnessing the advantages of deep learning techniques in a two-part process. (1) a 3D encoder-decoder, Rb-UNet, builds a localisation model and a 3D Tiramisu network generates a boundary-preserving segmentation model for each target structure; (2) the fully trained Rb-UNet predicts a 3D bounding box encapsulating the target structure of interest, after which the fully trained Tiramisu model performs segmentation to reveal detailed organ or muscle boundaries. The proposed approach is evaluated on six different datasets, including MRI, Dynamic Contrast Enhanced (DCE) MRI and CT scans targeting the pancreas, liver, kidneys and psoas-muscle and achieves quantitative measures of mean Dice similarity coefficient (DSC) that surpass or are comparable with the state-of-the-art. A qualitative evaluation performed by two independent radiologists verified the preservation of detailed organ and muscle boundaries.

Purpose: To investigate the ability of free induction decay navigator (FIDnav)-based motion monitoring to predict diagnostic utility and reduce the time and cost associated with acquiring diagnostically useful images in a pediatric patient cohort., Methods: A study was carried out in 102 pediatric patients (aged 0-18 years) at 3T using a 32-channel head coil array. Subjects were scanned with an FID-navigated MPRAGE sequence and images were graded by two radiologists using a five-point scale to evaluate the impact of motion artifacts on diagnostic image quality. The correlation between image quality and four integrated FIDnav motion metrics was investigated, as well as the sensitivity and specificity of each FIDnav-based metric to detect different levels of motion corruption in the images. Potential time and cost savings were also assessed by retrospectively applying an optimal detection threshold to FIDnav motion scores., Results: A total of 12% of images were rated as non-diagnostic, while a further 12% had compromised diagnostic value due to motion artifacts. FID-navigated metrics exhibited a moderately strong correlation with image grade (Spearman's rho ≥ 0.56). Integrating the cross-correlation between FIDnav signal vectors achieved the highest sensitivity and specificity for detecting non-diagnostic images, yielding total time savings of 7% across all scans. This corresponded to a financial benefit of $2080 in this study., Conclusions: Our results indicate that integrated motion metrics from FIDnavs embedded in structural MRI are a useful predictor of diagnostic image quality, which translates to substantial time and cost savings when applied to pediatric MRI examinations., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Diffusion-weighted MRI (DW-MRI) of the kidneys is a technique that provides information about the microstructure of renal tissue without requiring exogenous contrasts such as gadolinium, and it can be used for diagnosis in cases of renal disease and assessing response-to-therapy. However, physiological motion and large geometric distortions due to main B 0 field inhomogeneities degrade the image quality, reduce the accuracy of quantitative imaging markers, and impede their subsequent clinical applicability., Purpose: To retrospectively correct for geometric distortion for free-breathing DW-MRI of the kidneys at 3T, in the presence of a nonstatic distortion field due to breathing and bulk motion., Study Type: Prospective., Subjects: Ten healthy volunteers (ages 29-38, four females)., Field Strength/sequence: 3T; DW-MR dual-echo echo-planar imaging (EPI) sequence (10 b-values and 17 directions) and a T 2 volume., Assessment: The distortion correction was evaluated subjectively (Likert scale 0-5) and numerically with cross-correlation between the DW images at b = 0 s/mm 2 and a T 2 volume. The intravoxel incoherent motion (IVIM) and diffusion tensor (DTI) model-fitting performance was evaluated using the root-mean-squared error (nRMSE) and the coefficient of variation (CV%) of their parameters., Statistical Tests: Statistical comparisons were done using Wilcoxon tests., Results: The proposed method improved the Likert scores by 1.1 ± 0.8 (P < 0.05), the cross-correlation with the T 2 reference image by 0.13 ± 0.05 (P < 0.05), and reduced the nRMSE by 0.13 ± 0.03 (P < 0.05) and 0.23 ± 0.06 (P < 0.05) for IVIM and DTI, respectively. The CV% of the IVIM parameters (slow and fast diffusion, and diffusion fraction for IVIM and mean diffusivity, and fractional anisotropy for DTI) was reduced by 2.26 ± 3.98% (P = 6.971 × 10 -2 ), 11.24 ± 26.26% (P = 6.971 × 10 -2 ), 4.12 ± 12.91% (P = 0.101), 3.22 ± 0.55% (P < 0.05), and 2.42 ± 1.15% (P < 0.05)., Data Conclusion: The results indicate that the proposed Di + MoCo method can effectively correct for time-varying geometric distortions and for misalignments due to breathing motion. Consequently, the image quality and precision of the DW-MRI model parameters improved., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 1., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background Often used for T1 mapping of hip cartilage, three-dimensional (3D) dual-flip-angle (DFA) techniques are highly sensitive to flip angle variations related to B 1 inhomogeneities. The authors hypothesized that 3D magnetization-prepared 2 rapid gradient-echo (MP2RAGE) MRI would help provide more accurate T1 mapping of hip cartilage at 3.0 T than would 3D DFA techniques. Purpose To compare 3D MP2RAGE MRI with 3D DFA techniques using two-dimensional (2D) inversion recovery T1 mapping as a standard of reference for hip cartilage T1 mapping in phantoms, healthy volunteers, and participants with hip pain. Materials and Methods T1 mapping at 3.0 T was performed in phantoms and in healthy volunteers using 3D MP2RAGE MRI and 3D DFA techniques with B 1 field mapping for flip angle correction. Participants with hip pain prospectively (July 2019-January 2020) underwent indirect MR arthrography (with intravenous administration of 0.2 mmol/kg of gadoterate meglumine), including 3D MP2RAGE MRI. A 2D inversion recovery-based sequence served as a T1 reference in phantoms and in participants with hip pain. In healthy volunteers, cartilage T1 was compared between 3D MP2RAGE MRI and 3D DFA techniques. Paired t tests and Bland-Altman analysis were performed. Results Eleven phantoms, 10 healthy volunteers (median age, 27 years; range, 26-30 years; five men), and 20 participants with hip pain (mean age, 34 years ± 10 [standard deviation]; 17 women) were evaluated. In phantoms, T1 bias from 2D inversion recovery was lower for 3D MP2RAGE MRI than for 3D DFA techniques (mean, 3 msec ± 11 vs 253 msec ± 85; P < .001), and, unlike 3D DFA techniques, the deviation found with MP2RAGE MRI did not correlate with increasing B 1 deviation. In healthy volunteers, regional cartilage T1 difference (109 msec ± 163; P = .008) was observed only for the 3D DFA technique. In participants with hip pain, the mean T1 bias of 3D MP2RAGE MRI from 2D inversion recovery was -23 msec ± 31 ( P < .001). Conclusion Compared with three-dimensional (3D) dual-flip-angle techniques, 3D magnetization-prepared 2 rapid gradient-echo MRI enabled more accurate T1 mapping of hip cartilage, was less affected by B 1 inhomogeneities, and showed high accuracy against a T1 reference in participants with hip pain. © RSNA, 2021.

Purpose: To develop a method for slice-wise dynamic distortion correction for EPI using rapid spatiotemporal B 0 field measurements from FID navigators (FIDnavs) and to evaluate the efficacy of this new approach relative to an established data-driven technique., Methods: A low-resolution reference image was used to create a forward model of FIDnav signal changes to enable estimation of spatiotemporal B 0 inhomogeneity variations up to second order from measured FIDnavs. Five volunteers were scanned at 3 T using a 64-channel coil with FID-navigated EPI. The accuracy of voxel shift measurements and geometric distortion correction was assessed for experimentally induced magnetic field perturbations. The temporal SNR was evaluated in EPI time-series acquired at rest and with a continuous nose-touching action, before and after image realignment., Results: Field inhomogeneity coefficients and voxel shift maps measured using FIDnavs were in excellent agreement with multi-echo EPI measurements. The FID-navigated distortion correction accurately corrected image geometry in the presence of induced magnetic field perturbations, outperforming the data-driven approach in regions with large field offsets. In functional MRI scans with nose touching, FIDnav-based correction yielded temporal SNR gains of 30% in gray matter. Following image realignment, which accounted for global image shifts, temporal SNR gains of 3% were achieved., Conclusions: Our proposed application of FIDnavs enables slice-wise dynamic distortion correction with high temporal efficiency. We achieved improved signal stability by leveraging the encoding information from multichannel coils. This approach can be easily adapted to other EPI-based sequences to improve temporal SNR for a variety of clinical and research applications., (© 2020 International Society for Magnetic Resonance in Medicine.)

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 < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery., Interpretation: Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157., (© 2020 American Neurological Association.)

Background and Purpose: Little is known about microstructural development of cerebellar white matter in vivo. This study aimed to investigate developmental changes of the cerebellar peduncles in second- and third-trimester healthy fetuses using motion-corrected DTI and tractography., Materials and Methods: 3T data of 81 healthy fetuses were reviewed. Structural imaging consisted of multiplanar T2-single-shot sequences; DTI consisted of a series of 12-direction diffusion. A robust motion-tracked section-to-volume registration algorithm reconstructed images. ROI-based deterministic tractography was performed using anatomic landmarks described in postnatal tractography. Asymmetry was evaluated qualitatively with a perceived difference of >25% between sides. Linear regression evaluated gestational age as a predictor of tract volume, ADC, and fractional anisotropy., Results: Twenty-four cases were excluded due to low-quality reconstructions. Fifty-eight fetuses with a median gestational age of 30.6 weeks (interquartile range, 7 weeks) were analyzed. The superior cerebellar peduncle was identified in 39 subjects (69%), and it was symmetric in 15 (38%). The middle cerebellar peduncle was identified in all subjects and appeared symmetric; in 13 subjects (22%), two distinct subcomponents were identified. The inferior cerebellar peduncle was not found in any subject. There was a significant increase in volume for the superior cerebellar peduncle and middle cerebellar peduncle (both, P  < .05), an increase in fractional anisotropy (both, P  < .001), and a decrease in ADC (both, P  < .001) with gestational age. The middle cerebellar peduncle had higher volume ( P  < .001) and fractional anisotropy ( P  = .002) and lower ADC ( P  < .001) than the superior cerebellar peduncle after controlling for gestational age., Conclusions: A robust motion-tracked section-to-volume registration algorithm enabled deterministic tractography of the superior cerebellar peduncle and middle cerebellar peduncle in vivo and allowed characterization of developmental changes., (© 2021 by American Journal of Neuroradiology.)

Early identification of kidney function deterioration is essential to determine which newborn patients with congenital kidney disease should be considered for surgical intervention as opposed to observation. Kidney function can be measured by fitting a tracer kinetic (TK) model onto a series of Dynamic Contrast Enhanced (DCE) MR images and estimating the filtration rate parameter from the model. Unfortunately, breathing and large bulk motion events due to patient movement in the scanner create outliers and misalignments that introduce large errors in the TK model parameter estimates even when using a motion-robust dynamic radial VIBE sequence for DCE-MR imaging. The misalignments between the series of volumes are difficult to correct using standard registration due to 1) the large differences in geometry and contrast between volumes of the dynamic sequence and 2) the requirement of fast dynamic imaging to achieve high temporal resolution and motion deteriorates image quality. These difficulties reduce the accuracy and stability of registration over the dynamic sequence. An alternative registration approach is to generate noise and motion free templates of the original data from the TK model and use them to register each volume to its contrast-matched template. However, the TK models used to characterize DCE-MRI are tissue specific, non-linear and sensitive to the same motion and sampling artifacts that hinder registration in the first place. Hence, these can only be applied to register accurately pre-segmented regions of interest, such as kidneys, and might converge to local minima under the presence of large artifacts. Here we introduce a novel linear time invariant (LTI) model to characterize DCE-MR data for different tissue types within a volume. We approximate the LTI model as a sparse sum of first order LTI functions to introduce robustness to motion and sampling artifacts. Hence, this model is well suited for registration of the entire field of view of DCE-MR data with artifacts and outliers. We incorporate this LTI model into a registration framework and evaluate it on both synthetic data and data from 20 children. For each subject, we reconstructed the sequence of DCE-MR images, detected corrupted volumes acquired during motion, aligned the sequence of volumes and recovered the corrupted volumes using the LTI model. The results show that our approach correctly aligned the volumes, provided the most stable registration in time and improved the tracer kinetic model fit., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The trade-off between image resolution, signal-to-noise ratio (SNR), and scan time in any magnetic resonance imaging (MRI) protocol is inevitable and unavoidable. Super-resolution reconstruction (SRR) has been shown effective in mitigating these factors, and thus, has become an important approach in addressing the current limitations of MRI. In this work, we developed a novel, image-based MRI SRR approach based on anisotropic acquisition schemes, which utilizes a new gradient guidance regularization method that guides the high-resolution (HR) reconstruction via a spatial gradient estimate. Further, we designed an analytical solution to propagate the spatial gradient fields from the low-resolution (LR) images to the HR image space and exploited these gradient fields over multiple scales with a dynamic update scheme for more accurate edge localization in the reconstruction. We also established a forward model of image formation and inverted it along with the proposed gradient guidance. The proposed SRR method allows subject motion between volumes and is able to incorporate various acquisition schemes where the LR images are acquired with arbitrary orientations and displacements, such as orthogonal and through-plane origin-shifted scans. We assessed our proposed approach on simulated data as well as on the data acquired on a Siemens 3T MRI scanner containing 45 MRI scans from 14 subjects. Our experimental results demonstrate that our approach achieved superior reconstructions compared to state-of-the-art methods, both in terms of local spatial smoothness and edge preservation, while, in parallel, at reduced, or at the same cost as scans delivered with direct HR acquisition.