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.

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 (cm3) 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.

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.

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.

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.

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 (GABAA) 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.

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.