Journal Papers

2026

Valencia, Sergio, Emil Barkovich, Fedel Machado-Rivas, Phillip L Pearl, Simon K Warfield, Onur Afacan, and Camilo Jaimes. (2026) 2026. “Comparison of Myeloarchitectonic Feature Recognition of the Primary Visual Cortex at 7 T Relative to 3 T MRI.”. Journal of Magnetic Resonance Imaging : JMRI. https://doi.org/10.1002/jmri.70312.

BACKGROUND: The stria of Gennari (SoG) is a densely myelinated band within layer IVb of the primary visual cortex (V1) and represents the only cortical laminar structure visible macroscopically in vivo. Ultrahigh-field MRI may improve its detection and conspicuity.

PURPOSE: To quantitatively and qualitatively compare the in vivo appearance of the SoG at 3 versus 7 T using matched high-resolution T2-weighted fast spin-echo MRI.

STUDY TYPE: Prospective.

POPULATION: A total of 12 subjects (6 female, 6 male; median age, 17 years; range, 15-24 years) with pediatric-onset epilepsy.

FIELD STRENGTH/SEQUENCE: 3 and 7 T MRI, T2-weighted fast spin-echo, acquired within 1 month of each other.

ASSESSMENT: Cortical line profiles per subject were extracted orthogonally to the calcarine sulcus in V1. Quantitative metrics included peak-valley distance, Δ-signal (peak-valley difference), and contrast ratio (CR). Two blinded neuroradiologists and a radiologist independently rated SoG conspicuity using a 5-point Likert scale.

STATISTICAL TESTS: McNemar's test compared detection rates; paired t-tests or Wilcoxon signed-rank tests compared quantitative metrics; reader preferences were analyzed using Wilcoxon tests; inter-reader agreement was assessed using weighted Cohen's κ. No multiple-comparison correction was applied (α = 0.05).

RESULTS: SoG-consistent valleys were detected in 31% of profiles at 3 T and 65% at 7 T, significantly. Peak-valley distance remained stable across field strengths (0.45 ± 0.06 depth units; p = 0.37). Mean Δ-signal (33.5 vs. 36.1; p = 0.81) and contrast ratio (0.013 vs. 0.000; p = 0.54) did not differ significantly. Both readers demonstrated a strong preference for 7 T images (pseudo-median +1 to +1.5; significant), with fair inter-reader agreement (κ = 0.36).

DATA CONCLUSION: The SoG can be visualized in vivo at both 3 and 7 T, with higher detection frequency and greater subjective conspicuity at 7 T. Quantitative laminar metrics remained stable across field strengths, suggesting that improved detectability at 7 T likely reflects enhanced spatial definition rather than measurable changes in signal contrast.

TECHNICAL EFFICACY: Stage 2.

Valencia, Sergio, Fedel Machado-Rivas, Maria Camila Cortes-Albornoz, Samuel Cartmell, Harry Griffin, Darren B Orbach, Vanessa Rameh, et al. (2026) 2026. “7T TOF-MRA in Adolescents.”. AJNR. American Journal of Neuroradiology 47 (1): 262-68. https://doi.org/10.3174/ajnr.A8908.

BACKGROUND AND PURPOSE: The increased SNR at 7T enables higher spatial resolution for neurovascular imaging, yet its application in pediatric MRA remains underexplored. This study systematically evaluates the advantages of 7T TOF-MRA compared with 3T in pediatric patients, hypothesizing that 7T would provide superior vessel contrast and increased vascular volume, given the use of smaller voxels, as well as higher SNR, despite these smaller voxels.

MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act (HIPAA)-compliant, institutional review board-approved retrospective study included pediatric patients (younger than 19 years of age) who underwent 7T TOF-MRA. Controls consisted of either same-subject 3T MRAs within 6 months (when available) or age- and sex-matched 3T MRA subjects. Imaging parameters were optimized for spatial resolution at 7T to achieve 0.3- to 0.4-mm isotropic voxels. Quantitative analysis included contrast ratio and SNR measurements for the ICA, M1 to M4 arterial segments, and the lenticulostriate perforating arteries. Vascular volume was assessed using 3D segmentation. Semiquantitative vessel conspicuity ratings and motion artifact scoring were performed by blinded neuroradiologists.

RESULTS: Fifteen patients (10 with 7T MRA, 5 with matched 3T controls) and 20 MRAs were analyzed. Contrast ratio was significantly higher at 7T for perforators, M3, and M4 branches (P < .05), with the greatest improvement in the M4 branches. Vascular volume was 147% greater at 7T (P = .018), reflecting improved small-vessel depiction and segmentation. Semiquantitative analysis showed significantly better vessel conspicuity at 7T for the M4 branches and lenticulostriate perforators (P < .01). Motion artifact scores were similar between field strengths (P = .118).

CONCLUSIONS: 7T TOF-MRA significantly enhances vascular contrast and improves visualization of small arteries compared with 3T, making it a valuable tool for pediatric cerebrovascular imaging.

Timms, Liam, Mustafa Utkur, Cemre Ariyurek, Miriam Hewlett, Sila Kurugol, and Onur Afacan. (2026) 2026. “Fast, Robust T2-IVIM Quantitative MRI With Distortion and Motion-Corrected Multi-Echo EPI.”. Magnetic Resonance in Medicine 95 (5): 2527-37. https://doi.org/10.1002/mrm.70256.

PURPOSE: To enable robust, motion- and distortion-corrected T2-IVIM parameter estimation within clinically feasible scan times.

METHODS: A single-shot, multi-echo spin-echo EPI sequence was used to acquire abdominal diffusion-weighted MRI with time-efficient sampling of b-value and TE pairs. The multi-echo acquisition enabled distortion correction using reverse phase-encoding between echoes. Motion and distortion correction were applied before fitting a joint T2-IVIM model across the b-value and TE dimensions to obtain TE-independent IVIM parameters and compartment-specific T2 estimates. For comparison, a previously established single-echo T2-IVIM protocol with longer scan times and a single-echo protocol matched to the multi-echo parameters were acquired. Uncertainty was evaluated with wild bootstrap error analysis.

RESULTS: The multi-echo approach enabled motion- and distortion-corrected T2-IVIM mapping in under 5 min, compared with 11-13 min for the prior minimal single-echo protocol or nearly 19 min when acquired as separate shots. The liver was selected as the target organ due to its marked sensitivity to T 2 $$ {T}_2 $$ effects in standard IVIM. Error analysis showed comparable per-voxel uncertainty between the multi-echo method and the minimal single-echo protocol.

CONCLUSION: The combination of multi-echo sequence design and artifact correction enabled stable fitting of the extended T2-IVIM model with improved liver coverage and less than half the scan time of prior protocols. These advances support broader clinical applicability of T2-IVIM imaging by reducing acquisition burden while enhancing artifact correction and parameter robustness.

Taing, Matthew, Camilo Calixto, Onur Afacan, Maria Camila Cortes-Albornoz, Suely Fazio Ferracioll, Sergio Valencia, Clemente Velasco-Annis, Simon K Warfield, and Camilo Jaimes. (2026) 2026. “Super-Resolution MRI-Derived Brainstem and Cerebellar Volumes in Fetuses Between 22 Weeks and 32 weeks of Gestation.”. Pediatric Radiology. https://doi.org/10.1007/s00247-026-06574-6.

BACKGROUND: The posterior fossa undergoes rapid development in utero, yet normative volumetric data are limited, especially during mid-gestation when most fetal MRIs are performed.

OBJECTIVE: This study aimed to develop a segmentation method tailored to the fetal posterior fossa and establish normative growth trajectories for key infratentorial structures between 22 weeks and 32 weeks of gestation.

MATERIALS AND METHODS: Eighty-five pregnant women were prospectively recruited at a single institution. Inclusion criteria were normal singleton pregnancies between 19-40 weeks' gestation and maternal age 18-45 years. Exclusion criteria included fetal abnormalities, MRI contraindications, or significant maternal comorbidities. Eighteen fetuses were excluded, resulting in 67 normal fetuses (43 male, 24 female). Imaging was performed at 3 T using multiplanar T2-weighted sequences, reconstructed into isotropic volumes after motion correction and brain extraction. Segmentation labels were created using age-specific atlases from the Developing Human Connectome Project. Expert annotations defined the midbrain, pons, medulla, vermis, and cerebellar hemispheres. Images were registered to the atlases using the Symmetric Normalization (SyN) algorithm, with labels manually verified by a pediatric neuroradiologist. Volumes were normalized to total brain volume and analyzed using linear regression with gestational age and sex as predictors.

RESULTS: Absolute volumes of all posterior fossa structures significantly increased with gestational age (P<0.001), showing strong linear associations (R2=0.80-0.87). The cerebellum exhibited the steepest growth (β=1,056.01, R2=0.87, P<0.001). Growth was symmetric with no significant left-right differences. Relative volumetric trends varied: the cerebellum increased proportionally (β=0.007, P<0.001), while the midbrain, pons, and medulla decreased relative to total brain volume. The vermis showed no significant association with gestational age but had sex-specific effects; males had smaller relative vermian volumes than females (β=-0.43, P=0.04), despite larger absolute posterior fossa volumes overall.

CONCLUSIONS: This study provides normative volumetric references for fetal posterior fossa structures between 22-32 weeks' gestation using a novel segmentation method. Absolute growth followed linear patterns, while relative measures revealed sex-specific variations in the vermis and cerebellum. These benchmarks may enhance diagnostic accuracy for detecting posterior fossa anomalies in clinical fetal MRI.

2025

Kertes, Noga, Yael Zaffrani-Reznikov, Onur Afacan, Sila Kurugol, Simon K Warfield, and Moti Freiman. (2025) 2025. “IVIM-Morph: Motion-Compensated Quantitative Intra-Voxel Incoherent Motion (IVIM) Analysis for Functional Fetal Lung Maturity Assessment from Diffusion-Weighted MRI Data.”. ArXiv.

Quantitative analysis of pseudo-diffusion in diffusion-weighted magnetic resonance imaging (DWI) data shows potential for assessing fetal lung maturation and generating valuable imaging biomarkers. Yet, the clinical utility of DWI data is hindered by unavoidable fetal motion during acquisition. We present IVIM-morph, a self-supervised deep neural network model for motion-corrected quantitative analysis of DWI data using the Intra-voxel Incoherent Motion (IVIM) model. IVIM-morph combines two sub-networks, a registration sub-network, and an IVIM model fitting sub-network, enabling simultaneous estimation of IVIM model parameters and motion. To promote physically plausible image registration, we introduce a biophysically informed loss function that effectively balances registration and model-fitting quality. We validated the efficacy of IVIM-morph by establishing a correlation between the predicted IVIM model parameters of the lung and gestational age (GA) using fetal DWI data of 39 subjects. Our approach was compared against six baseline methods: 1) no motion compensation, 2) affine registration of all DWI images to the initial image, 3) deformable registration of all DWI images to the initial image, 4) deformable registration of each DWI image to its preceding image in the sequence, 5) iterative deformable motion compensation combined with IVIM model parameter estimation, and 6) self-supervised deep-learning-based deformable registration. IVIM-morph exhibited a notably improved correlation with gestational age (GA) when performing in-vivo quantitative analysis of fetal lung DWI data during the canalicular phase. Specifically, over 2 test groups of cases, it achieved an R f 2 of 0.44 and 0.52, outperforming the values of 0.27 and 0.25, 0.25 and 0.00, 0.00 and 0.00, 0.38 and 0.00, and 0.07 and 0.14 obtained by other methods. IVIM-morph shows potential in developing valuable biomarkers for non-invasive assessment of fetal lung maturity with DWI data. Moreover, its adaptability opens the door to potential applications in other clinical contexts where motion compensation is essential for quantitative DWI analysis. The IVIM-morph code is readily available at:https://github.com/TechnionComputationalMRILab/qDWI-Morph.

Wang, Xiaoqing, Hongli Fan, Zhengguo Tan, Serge Vasylechko, Edward Yang, Ryne Didier, Onur Afacan, Martin Uecker, Simon K Warfield, and Ali Gholipour. (2025) 2025. “Rapid, High-Resolution and Distortion-FreeR 2 *Mapping of Fetal Brain Using Multi-Echo Radial FLASH and Model-Based Reconstruction.”. ArXiv.

PURPOSE: To develop a rapid, high-resolution and distortion-free technique for simultaneous water-fat separation, R 2 * and B 0 mapping of the fetal brain at 3T.

METHODS: A 2D multi-echo radial FLASH sequence with blip gradients is adapted for data acquisition during maternal free breathing. A calibrationless model-based reconstruction with sparsity constraints is developed to jointly estimate water, fat, R 2 * and B 0 field maps directly from k-space. This approach was validated and compared to reference methods using numerical and NIST phantoms and data from nine fetuses between 26 and 36 weeks of gestation age.

RESULTS: Both numerical and experimental phantom studies confirm good accuracy and precision. In fetal studies, model-based reconstruction yields quantitative R 2 * values in close agreement with those from a parallel imaging compressed sensing (PICS) technique using Graph Cut (intra-class correlation coefficient [ICC] = 0.9601), while providing enhanced image detail. Repeated scans confirm good reproducibility (ICC = 0.9213). Compared to multi-echo EPI, the proposed radial technique produces higher-resolution (1.1 × 1.1 × 3 mm3 vs. 2-3 × 2-3 × 3 mm3) R 2 * maps with reduced distortion. Despite of differences in motion, resolution and distortion, R 2 * values are comparable between the two acquisition strategies (ICC = 0.8049). Additionally, the proposed approach enables synthesis of high-resolution and distortion-free R 2 * -weighted images.

CONCLUSION: This study demonstrates the feasibility of using multi-echo radial FLASH combined with calibrationless model-based reconstruction for motion-robust, distortion-free R 2 * mapping of the fetal brain at 3T, achieving a nominal resolution of 1.1 × 1.1 × 3 mm3 within 2 seconds per slice.

Calixto, Camilo, Maria C Cortes-Albornoz, Clemente Velasco-Annis, Davood Karimi, Onur Afacan, Simon K Warfield, Ali Gholipour, and Camilo Jaimes. (2025) 2025. “Regional Changes in the Fetal Telencephalic Wall Diffusion Metrics Across Late Second and Third Trimesters.”. Human Brain Mapping 46 (3): e70159. https://doi.org/10.1002/hbm.70159.

During the second and third trimesters of human gestation, the brain undergoes rapid neurodevelopment thanks to critical processes such as neuronal migration, radial glial scaffolding, and synaptic sprouting. Unfortunately, gathering high-quality MRI data on the healthy fetal brain is complex, making it challenging to understand this development. To address this issue, we conducted a study using motion-corrected diffusion tensor imaging (DTI) to analyze changes in the cortical gray matter (CP) and sub-cortical white matter (scWM) microstructure in 44 healthy fetuses between 23 and 36 weeks of gestational age. We automatically segmented these two tissues and parcellated them into eight regions based on anatomy, including the frontal, parietal, occipital, and temporal lobes, cingulate, sensory and motor cortices, and the insula. We were able to observe distinct patterns of diffusion MRI signals across these regions. Specifically, we found that in the CP, fractional anisotropy (FA) consistently decreased with age, while mean diffusivity (MD) followed a downward-open parabolic trend. Conversely, in the scWM, FA exhibited an upward-open parabolic trajectory, while MD followed a downward-open parabolic trend. Our study underscores the potential for diffusion as a biomarker for normal and abnormal neurodevelopment before birth, especially since most neurodiagnostic tools are not yet available at this stage.

Latzer, Itay Tokatly, Ellen Hanson, Mariarita Bertoldi, Melissa L DiBacco, Deniz Aygun, Onur Afacan, Àngeles García-Cazorla, et al. (2025) 2025. “The Neuropsychological Profile of SSADH Deficiency, a Neurotransmitter Disorder of GABA Metabolism.”. Molecular Genetics and Metabolism 144 (3): 109051. https://doi.org/10.1016/j.ymgme.2025.109051.

BACKGROUND AND OBJECTIVES: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder resulting in hyper-physiologic concentrations of the neurotransmitter γ-aminobutyrate (GABA). This study aims to provide the most comprehensive description, to date, of the neuropsychological profile of individuals with SSADHD and assess whether neuroimaging, neurophysiologic, and biochemical indices of cortical inhibition correlate with those of standardized behavioral tests.

METHODS: Participants enrolled in the SSADHD Natural History Study underwent medical and neurological examinations, magnetic resonance imaging (MRI) and spectroscopy (MRS), biochemical tests of GABA and its related metabolites, transcranial magnetic stimulation (TMS), and gene expression quantification, as well as complete neuropsychological assessment including standardized measures for cognition, adaptive skills, motor function, receptive and expressive language, autism spectrum disorder, and behavior problems.

RESULTS: The neuropsychological profile of the study's 65 enrollees [54 % females, median (interquartile range) age 9.6 (5.4-14.7)] consisted almost universally of intellectual disability, delays in adaptive skills, and deficits in expressive more than receptive language. Autism Spectrum Disorder was noted in ∼50 %, and behavioral problems in ∼70 %, predominated by obsessive-compulsive behaviors and attention problems but also including affective problems, anxiety, and, rarely, aggression and possible psychosis. Correlation analyses showed that increased internalizing, externalizing, and overall psychiatric morbidity significantly correlated with increasing age (R = 0.391, p = 0.033), as well as age-independent indices representing decreased cortical inhibition such as lower MRS-derived GABA (R = -0.530, p = 0.029) and TMS-derived resting motor threshold (R = -0.418, p = 0.053).

DISCUSSION: The natural history study of SSADHD indicates that intellectual disability, delayed adaptive skills, and expressive>receptive language deficits are nearly universal, with behavior problems in the vast majority. Increased psychiatric morbidity in SSADHD with age-independent decreased cortical inhibition may serve as the basis for establishing disorder-specific biomarkers for behavioral and psychiatric outcomes in SSADHD and other non-syndromic psychiatric disorders.

Meier, Malin Kristin, Ramon Andreas Helfenstein, Adam Boschung, Andreas Nanavati, Adrian Ruckli, Till D Lerch, Nicolas Gerber, et al. (2025) 2025. “A Deep Learning Approach for Automatic 3D Segmentation of Hip Cartilage and Labrum from Direct Hip MR Arthrography.”. Scientific Reports 15 (1): 4662. https://doi.org/10.1038/s41598-025-86727-z.

The objective was to use convolutional neural networks (CNNs) for automatic segmentation of hip cartilage and labrum based on 3D MRI. In this retrospective single-center study, CNNs with a U-Net architecture were used to develop a fully automated segmentation model for hip cartilage and labrum from MRI. Direct hip MR arthrographies (01/2020-10/2021) were selected from 100 symptomatic patients. Institutional routine protocol included a 3D T1 mapping sequence, which was used for manual segmentation of hip cartilage and labrum. 80 hips were used for training and the remaining 20 for testing. Model performance was assessed with six evaluation metrics including Dice similarity coefficient (DSC). In addition, model performance was tested on an external dataset (40 patients) with a 3D T2-weighted sequence from a different institution. Inter-rater agreement of manual segmentation served as benchmark for automatic segmentation performance. 100 patients were included (mean age 30 ± 10 years, 64% female patients). Mean DSC for cartilage was 0.92 ± 0.02 (95% confidence interval [CI] 0.92-0.93) and 0.83 ± 0.04 (0.81-0.85) for labrum and comparable (p = 0.232 and 0.297, respectively) to inter-rater agreement of manual segmentation: DSC cartilage 0.93 ± 0.04 (0.92-0.95); DSC labrum 0.82 ± 0.05 (0.80-0.85). When tested on the external dataset, the DSC was 0.89 ± 0.02 (0.88-0.90) and 0.71 ± 0.04 (0.69-0.73) for cartilage and labrum, respectively.The presented deep learning approach accurately segments hip cartilage and labrum from 3D MRI sequences and can potentially be used in clinical practice to provide rapid and accurate 3D MRI models.

Valencia, Sergio, Fedel Machado-Rivas, Arman Avesta, Emil J Barkovich, Samuel C D Cartmell, Simon K Warfield, Camilo Jaimes, and Onur Afacan. (2025) 2025. “Optimizing T2* Imaging for Adolescent and Young Adult Patients at 7 T.”. Pediatric Radiology 55 (6): 1138-47. https://doi.org/10.1007/s00247-025-06213-6.

BACKGROUND: T2*-weighted imaging at 7 T offers detailed visualization of brain structures, but image quality and artifacts depend on echo time (TE) adjustments. Optimizing TE is crucial for tissue contrast and artifact minimization.

OBJECTIVE: To evaluate the impact of TE on tissue contrast and image quality in T2*-weighted sequences at 7 T in adolescents and young adults.

MATERIALS AND METHODS: Ten adolescent and young adult patients underwent 7-T MRI with multi-echo T2*-weighted sequences. Six TEs (8.1 ms to 36 ms) were acquired. Signal contrast ratios (CR) for seven brain regions-caudate nuclei, corpus callosum genu, frontal cortex, cortical veins, globi pallidi, medullary veins, and left optic radiation-were analyzed. Two blinded neuroradiologists assessed image quality and artifact severity using a 4-point Likert scale (IQS). Statistical trends were analyzed using the Jonckheere-Terpstra test. A P-value < 0.05 was considered statistically significant.

RESULTS: The study cohort consisted of 4 male and 6 females; the median age of the patients was 16 years (range 15-23 years). CR increased significantly with higher TEs for most regions except the caudate, where CR decreased (P < 0.05). Longer TEs led to greater artifact severity in the brainstem, temporal, occipital, and frontal lobes (P < 0.02), but not in parietal lobes (P > 0.05). Kappa agreement for IQS was 0.76.

CONCLUSION: TE significantly affects contrast and artifacts in 7-T T2*-weighted imaging. TEs between 20 and 30 ms offer the best balance between tissue contrast and artifact severity, optimizing image quality for clinical and research applications.