Journal Papers

F

Khan, Shadab, Lana Vasung, Bahram Marami, Caitlin Rollins, Onur Afacan, Cynthia Ortinau, Edward Yang, Simon Warfield, and Ali Gholipour. 2019. “Fetal Brain Growth Portrayed by a Spatiotemporal Diffusion Tensor MRI Atlas Computed from in Utero Images”. Neuroimage 185: 593-608. https://doi.org/10.1016/j.neuroimage.2018.08.030.
Altered structural fetal brain development has been linked to neuro-developmental disorders. These structural alterations can be potentially detected in utero using diffusion tensor imaging (DTI). However, acquisition and reconstruction of in utero fetal brain DTI remains challenging. Until now, motion-robust DTI methods have been employed for reconstruction of in utero fetal DTIs. However, due to the unconstrained fetal motion and permissible in utero acquisition times, these methods yielded limited success and have typically resulted in noisy DTIs. Consequently, atlases and methods that could enable groupwise studies, multi-modality imaging, and computer-aided diagnosis from in utero DTIs have not yet been developed. This paper presents the first DTI atlas of the fetal brain computed from in utero diffusion-weighted images. For this purpose an algorithm for computing an unbiased spatiotemporal DTI atlas, which integrates kernel-regression in age with a diffeomorphic tensor-to-tensor registration of motion-corrected and reconstructed individual fetal brain DTIs, was developed. Our new algorithm was applied to a set of 67 fetal DTI scans acquired from healthy fetuses each scanned at a gestational age between 21 and 39 weeks. The neurodevelopmental trends in the fetal brain, characterized by the atlas, were qualitatively and quantitatively compared with the observations reported in prior ex vivo and in utero studies, and with results from imaging gestational-age equivalent preterm infants. Our major findings revealed early presence of limbic fiber bundles, followed by the appearance and maturation of projection pathways (characterized by an age related increase in FA) during late 2nd and early 3rd trimesters. During the 3rd trimester association fiber bundles become evident. In parallel with the appearance and maturation of fiber bundles, from 21 to 39 gestational weeks gradual disappearance of the radial coherence of the telencephalic wall was qualitatively identified. These results and analyses show that our DTI atlas of the fetal brain is useful for reliable detection of major neuronal fiber bundle pathways and for characterization of the fetal brain reorganization that occurs in utero. The atlas can also serve as a useful resource for detection of normal and abnormal fetal brain development in utero.
Kurugol, Sila, Catherine Seager, Hatim Thaker, Jaume Coll-Font, Onur Afacan, Reid Nichols, Simon Warfield, Richard Lee, and Jeanne Chow. (2020) 2020. “Feed and Wrap Magnetic Resonance Urography Provides Anatomic and Functional Imaging in Infants Without Anesthesia”. J Pediatr Urol 16 (1): 116-20. https://doi.org/10.1016/j.jpurol.2019.11.002.
OBJECTIVE: To describe a technique for performing magnetic resonance urogram (MRU) in infants without sedation or anesthesia. METHODS: Eighteen infants underwent MRU in the absence of sedating medications using a 'feed and wrap' technique (FW-MRU). Dynamic contrast enhanced images were obtained. Dynamic radial VIBE and compressed sensing image reconstruction were used to correct for motion artifact. RESULTS: Seventeen of the 18 patients had successful FW-MRU. Feed and wrap' magnetic resonance urogram provided high-quality anatomic and functional renal data. CONCLUSION: Initial experience with FW-MRU demonstrates it to be a promising anesthesia-free modality for obtaining anatomic and functional imaging of the urinary tract in infants.
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. 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.

Akhondi-Asl, Alireza, Onur Afacan, Mukund Balasubramanian, Robert Mulkern, and Simon Warfield. 2016. “Fast Myelin Water Fraction Estimation Using 2D Multislice CPMG”. Magn Reson Med 76 (4): 1301-13. https://doi.org/10.1002/mrm.26034.
PURPOSE: T2 relaxometry based on multiexponential fitting to a single slice multiecho sequence has been the most common MRI technique for myelin water fraction mapping, where the short T2 is associated with myelin water. However, very long acquisition times and physically unrealistic models for T2 distribution are limitations of this approach. We present a novel framework for myelin imaging which substantially increases the imaging speed and myelin water fraction estimation accuracy. METHOD: We used the 2D multislice Carr-Purcell-Meiboom-Gill sequence to increase the volume coverage. To compensate for nonideal slice profiles, we numerically solved the Bloch equations for a range of T2 and B1 inhomogeneity scales to construct the bases for the estimation of the T2 distribution. We used a finite mixture of continuous parametric distributions to describe the complete T2 spectrum and used the constrained variable projection optimization algorithm to estimate myelin water fraction. To validate our model, synthetic, phantom, and in vivo brain experiments were conducted. RESULTS: Using the Bloch equations, we can model the slice profile and construct the forward model of the T2 curve. Our method estimated myelin water fraction with smaller error than the nonnegative least squares algorithm. CONCLUSIONS: The proposed framework can be used for reliable whole brain myelin imaging with a resolution of 2×2×4  mm3 in ≈17  min. Magn Reson Med 76:1301-1313, 2016. © 2015 Wiley Periodicals, Inc.
Sui, Yao, Onur Afacan, Ali Gholipour, and Simon Warfield. (2021) 2021. “Fast and High-Resolution Neonatal Brain MRI Through Super-Resolution Reconstruction From Acquisitions With Variable Slice Selection Direction”. Front Neurosci 15: 636268. https://doi.org/10.3389/fnins.2021.636268.
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.

E

Machado-Rivas, Fedel, Camilo Jaimes, Benoit Scherrer, Leslie Benson, Mark Gorman, Simon Warfield, and Onur Afacan. 2022. “Evaluation of White Matter Microstructure in Pediatric Onset Multiple Sclerosis With Diffusion Compartment Imaging”. J Neuroimaging. https://doi.org/10.1111/jon.13038.
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.
Afacan, Onur, Burak Erem, Diona Roby, Noam Roth, Amir Roth, Sanjay Prabhu, and Simon Warfield. (2016) 2016. “Evaluation of Motion and Its Effect on Brain Magnetic Resonance Image Quality in Children”. Pediatr Radiol 46 (12): 1728-35. https://doi.org/10.1007/s00247-016-3677-9.
BACKGROUND: Motion artifacts pose significant problems for the acquisition of MR images in pediatric populations. OBJECTIVE: To evaluate temporal motion metrics in MRI scanners and their effect on image quality in pediatric populations in neuroimaging studies. MATERIALS AND METHODS: We report results from a large pediatric brain imaging study that shows the effect of motion on MRI quality. We measured motion metrics in 82 pediatric patients, mean age 13.4 years, in a T1-weighted brain MRI scan. As a result of technical difficulties, 5 scans were not included in the subsequent analyses. A radiologist graded the images using a 4-point scale ranging from clinically non-diagnostic because of motion artifacts to no motion artifacts. We used these grades to correlate motion parameters such as maximum motion, mean displacement from a reference point, and motion-free time with image quality. RESULTS: Our results show that both motion-free time (as a ratio of total scan time) and average displacement from a position at a fixed time (when the center of k-space was acquired) were highly correlated with image quality, whereas maximum displacement was not as good a predictor. Among the 77 patients whose motion was measured successfully, 17 had average displacements of greater than 0.5 mm, and 11 of those (14.3%) resulted in non-diagnostic images. Similarly, 14 patients (18.2%) had less than 90% motion-free time, which also resulted in non-diagnostic images. CONCLUSION: We report results from a large pediatric study to show how children and young adults move in the MRI scanner and the effect that this motion has on image quality. The results will help the motion-correction community in better understanding motion patterns in pediatric populations and how these patterns affect MR image quality.
Ortinau, Cynthia, Caitlin Rollins, Ali Gholipour, Hyuk Jin Yun, Mackenzie Marshall, Borjan Gagoski, Onur Afacan, et al. 2019. “Early-Emerging Sulcal Patterns Are Atypical in Fetuses With Congenital Heart Disease”. Cereb Cortex 29 (8): 3605-16. https://doi.org/10.1093/cercor/bhy235.
Fetuses with congenital heart disease (CHD) have third trimester alterations in cortical development on brain magnetic resonance imaging (MRI). However, the intersulcal relationships contributing to global sulcal pattern remain unknown. This study applied a novel method for examining the geometric and topological relationships between sulci to fetal brain MRIs from 21-30 gestational weeks in CHD fetuses (n = 19) and typically developing (TD) fetuses (n = 17). Sulcal pattern similarity index (SI) to template fetal brain MRIs was determined for the position, area, and depth for corresponding sulcal basins and intersulcal relationships for each subject. CHD fetuses demonstrated altered global sulcal patterns in the left hemisphere compared with TD fetuses (TD [SI, mean ± SD]: 0.822 ± 0.023, CHD: 0.795 ± 0.030, P = 0.002). These differences were present in the earliest emerging sulci and were driven by differences in the position of corresponding sulcal basins (TD: 0.897 ± 0.024, CHD: 0.878 ± 0.019, P = 0.006) and intersulcal relationships (TD: 0.876 ± 0.031, CHD: 0.857 ± 0.018, P = 0.033). No differences in cortical gyrification index, mean curvature, or surface area were present. These data suggest our methods may be more sensitive than traditional measures for evaluating cortical developmental alterations early in gestation.

D

Wallace, Tess, Jonathan Polimeni, Jason Stockmann, Scott Hoge, Tobias Kober, Simon Warfield, and Onur Afacan. 2021. “Dynamic Distortion Correction for Functional MRI Using FID Navigators”. Magn Reson Med 85 (3): 1294-1307. https://doi.org/10.1002/mrm.28505.
PURPOSE: To develop a method for slice-wise dynamic distortion correction for EPI using rapid spatiotemporal B0 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 B0 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.

C

Kurugol, Sila, Onur Afacan, Richard Lee, Catherine Seager, Michael Ferguson, Deborah Stein, Reid Nichols, et al. (2020) 2020. “Correction To: Prospective Pediatric Study Comparing Glomerular Filtration Rate Estimates Based on Motion-Robust Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Serum Creatinine (eGFR) to Tc DTPA”. Pediatr Radiol 50 (5): 755-56. https://doi.org/10.1007/s00247-020-04654-9.
The originally published version of this article contained a typographical error. In the text under the subheading "Dynamic contrast-enhanced MRI method, post-processing, and MR-GFR calculation" and in Table 1 the intravenous injection rate of gadobutrol was incorrectly listed as 0.2 mL/s.