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.

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.

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.

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 B0 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 T2 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/mm2 and a T2 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 T2 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.

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.

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.

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 B1 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 B1 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 B1 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 B1 inhomogeneities, and showed high accuracy against a T1 reference in participants with hip pain. © RSNA, 2021.

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.

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.