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2019

Afacan, Onur, Judy Estroff, Edward Yang, Carol Barnewolt, Susan Connolly, Richard Parad, Robert Mulkern, Simon Warfield, and Ali Gholipour. (2019) 2019. “Fetal Echoplanar Imaging: Promises and Challenges”. Top Magn Reson Imaging 28 (5): 245-54. https://doi.org/10.1097/RMR.0000000000000219.
Fetal magnetic resonance imaging (MRI) has been gaining increasing interest in both clinical radiology and research. Echoplanar imaging (EPI) offers a unique potential, as it can be used to acquire images very fast. It can be used to freeze motion, or to get multiple images with various contrast mechanisms that allow studying the microstructure and function of the fetal brain and body organs. In this article, we discuss the current clinical and research applications of fetal EPI. This includes T2*-weighted imaging to better identify blood products and vessels, using diffusion-weighted MRI to investigate connections of the developing brain and using functional MRI (fMRI) to identify the functional networks of the developing brain. EPI can also be used as an alternative structural sequence when banding or standing wave artifacts adversely affect the mainstream sequences used routinely in structural fetal MRI. We also discuss the challenges with EPI acquisitions, and potential solutions. As EPI acquisitions are inherently sensitive to susceptibility artifacts, geometric distortions limit the use of high-resolution EPI acquisitions. Also, interslice motion and transmit and receive field inhomogeneities may create significant artifacts in fetal EPI. We conclude by discussing promising research directions to overcome these challenges to improve the use of EPI in clinical and research applications.
Peters, Jurriaan, Robbert Struyven, Anna Prohl, Lana Vasung, Andrija Stajduhar, Maxime Taquet, John Bushman, et al. 2019. “White Matter Mean Diffusivity Correlates With Myelination in Tuberous Sclerosis Complex”. Ann Clin Transl Neurol 6 (7): 1178-90. https://doi.org/10.1002/acn3.793.
OBJECTIVE: Diffusion tensor imaging (DTI) of the white matter is a biomarker for neurological disease burden in tuberous sclerosis complex (TSC). To clarify the basis of abnormal diffusion in TSC, we correlated ex vivo high-resolution diffusion imaging with histopathology in four tissue types: cortex, tuber, perituber, and white matter. METHODS: Surgical specimens of three children with TSC were scanned in a 3T or 7T MRI with a structural image isotropic resolution of 137-300 micron, and diffusion image isotropic resolution of 270-1,000 micron. We stained for myelin (luxol fast blue, LFB), gliosis (glial fibrillary acidic protein, GFAP), and neurons (NeuN) and registered the digitized histopathology slides (0.686 micron resolution) to MRI for visual comparison. We then performed colocalization analysis in four tissue types in each specimen. Finally, we applied a linear mixed model (LMM) for pooled analysis across the three specimens. RESULTS: In white matter and perituber regions, LFB optical density measures correlated with fractional anisotropy (FA) and inversely with mean diffusivity (MD). In white matter only, GFAP correlated with MD, and inversely with FA. In tubers and in the cortex, there was little variation in mean LFB and GFAP signal intensity, and no correlation with MRI metrics. Neuronal density correlated with MD. In the analysis of the combined specimens, the most robust correlation was between white matter MD and LFB metrics. INTERPRETATION: In TSC, diffusion imaging abnormalities in microscopic tissue types correspond to specific histopathological markers. Across all specimens, white matter diffusivity correlates with myelination.
Cole, Alexis, Dorothy Perry, Ali Raza, Arthur Nedder, Elizabeth Pollack, William Regan, Sarah Bosch, et al. (2019) 2019. “Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine”. JACC Basic Transl Sci 4 (2): 176-87. https://doi.org/10.1016/j.jacbts.2018.11.006.
This study used a swine model of mildly hypothermic prolonged circulatory arrest and found that the addition of 2.4% inhaled hydrogen gas to inspiratory gases during and after the ischemic insult significantly decreased neurologic and renal injury compared with controls. With proper precautions, inhalational hydrogen may be administered safely through conventional ventilators and may represent a complementary therapy that can be easily incorporated into current workflows. In the future, inhaled hydrogen may diminish the sequelae of ischemia that occurs in congenital heart surgery, cardiac arrest, extracorporeal life-support events, acute myocardial infarction, stroke, and organ transplantation.
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.
Wallace, Tess, Onur Afacan, Maryna Waszak, Tobias Kober, and Simon Warfield. 2019. “Head Motion Measurement and Correction Using FID Navigators”. Magn Reson Med 81 (1): 258-74. https://doi.org/10.1002/mrm.27381.
PURPOSE: To develop a novel framework for rapid, intrinsic head motion measurement in MRI using FID navigators (FIDnavs) from a multichannel head coil array. METHODS: FIDnavs encode substantial rigid-body motion information; however, current implementations require patient-specific training with external tracking data to extract quantitative positional changes. In this work, a forward model of FIDnav signals was calibrated using simulated movement of a reference image within a model of the spatial coil sensitivities. A FIDnav module was inserted into a nonselective 3D FLASH sequence, and rigid-body motion parameters were retrospectively estimated every readout time using nonlinear optimization to solve the inverse problem posed by the measured FIDnavs. This approach was tested in simulated data and in 7 volunteers, scanned at 3T with a 32-channel head coil array, performing a series of directed motion paradigms. RESULTS: FIDnav motion estimates achieved mean absolute errors of 0.34 ± 0.49 mm and 0.52 ± 0.61° across all subjects and scans, relative to ground-truth motion measurements provided by an electromagnetic tracking system. Retrospective correction with FIDnav motion estimates resulted in substantial improvements in quantitative image quality metrics across all scans with intentional head motion. CONCLUSIONS: Quantitative rigid-body motion information can be effectively estimated using the proposed FIDnav-based approach, which represents a practical method for retrospective motion compensation in less cooperative patient populations.
Marami, Bahram, Benoit Scherrer, Shadab Khan, Onur Afacan, Sanjay Prabhu, Mustafa Sahin, Simon Warfield, and Ali Gholipour. 2019. “Motion-Robust Diffusion Compartment Imaging Using Simultaneous Multi-Slice Acquisition”. Magn Reson Med 81 (5): 3314-29. https://doi.org/10.1002/mrm.27613.
PURPOSE: To achieve motion-robust diffusion compartment imaging (DCI) in near continuously moving subjects based on simultaneous multi-slice, diffusion-weighted brain MRI. METHODS: Simultaneous multi-slice (SMS) acquisition enables fast and dense sampling of k- and q-space. We propose to achieve motion-robust DCI via slice-level motion correction by exploiting the rigid coupling between simultaneously acquired slices. This coupling provides 3D coverage of the anatomy that substantially constraints the slice-to-volume alignment problem. This is incorporated into an explicit model of motion dynamics that handles continuous and large subject motion in robust DCI reconstruction. RESULTS: We applied the proposed technique, called Motion Tracking based on Simultanous Multislice Registration (MT-SMR) to multi b-value SMS diffusion-weighted brain MRI of healthy volunteers and motion-corrupted scans of 20 pediatric subjects. Quantitative and qualitative evaluation based on fractional anisotropy in unidirectional fiber regions, and DCI in crossing-fiber regions show robust reconstruction in the presence of motion. CONCLUSION: The proposed approach has the potential to extend routine use of SMS DCI in very challenging populations, such as young children, newborns, and non-cooperative patients.
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.
Marami, Bahram, Benoit Scherrer, Shadab Khan, Onur Afacan, Sanjay P Prabhu, Mustafa Sahin, Simon K Warfield, and Ali Gholipour. (2019) 2019. “Motion-Robust Diffusion Compartment Imaging Using Simultaneous Multi-Slice Acquisition.”. Magnetic Resonance in Medicine 81 (5): 3314-29. https://doi.org/10.1002/mrm.27613.
Publisher's Version
Publisher's Version

PURPOSE: To achieve motion-robust diffusion compartment imaging (DCI) in near continuously moving subjects based on simultaneous multi-slice, diffusion-weighted brain MRI.

METHODS: Simultaneous multi-slice (SMS) acquisition enables fast and dense sampling of k- and q-space. We propose to achieve motion-robust DCI via slice-level motion correction by exploiting the rigid coupling between simultaneously acquired slices. This coupling provides 3D coverage of the anatomy that substantially constraints the slice-to-volume alignment problem. This is incorporated into an explicit model of motion dynamics that handles continuous and large subject motion in robust DCI reconstruction.

RESULTS: We applied the proposed technique, called Motion Tracking based on Simultanous Multislice Registration (MT-SMR) to multi b-value SMS diffusion-weighted brain MRI of healthy volunteers and motion-corrupted scans of 20 pediatric subjects. Quantitative and qualitative evaluation based on fractional anisotropy in unidirectional fiber regions, and DCI in crossing-fiber regions show robust reconstruction in the presence of motion.

CONCLUSION: The proposed approach has the potential to extend routine use of SMS DCI in very challenging populations, such as young children, newborns, and non-cooperative patients.

2018

Martinot, Amanda, Peter Abbink, Onur Afacan, Anna Prohl, Roderick Bronson, Jonathan Hecht, Erica Borducchi, et al. 2018. “Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys”. Cell 173 (5): 1111-1122.e10. https://doi.org/10.1016/j.cell.2018.03.019.
The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.
Khan, Shadab, Caitlin K Rollins, Cynthia M Ortinau, Onur Afacan, Simon K Warfield, and Ali Gholipour. (2018) 2018. “Tract-Specific Group Analysis in Fetal Cohorts Using in Utero Diffusion Tensor Imaging.”. Medical Image Computing and Computer-Assisted Intervention : MICCAI . International Conference on Medical Image Computing and Computer-Assisted Intervention 11072: 28-35. https://doi.org/10.1007/978-3-030-00931-1_4.
Publisher's Version
Publisher's Version

Diffusion tensor imaging (DTI) based group analysis has helped uncover the impact of white matter injuries in a wide range of studies involving subjects from preterm neonates to adults. The application of these methods to fetal cohorts, however, has been hampered by the challenging nature of in utero fetal DTI caused by unconstrained fetal motion, limited scan times, and limited signal-to-noise ratio. We present a framework that addresses these issues to systematically evaluate group differences in fetal cohorts. A motion-robust DTI computation approach with a new unbiased DTI template construction method is unified with kernel-regression in age and tensor-specific registration to normalize DTI volumes in an unbiased space. A robust statistical approach is used to map region-specific group differences to the medial representation of the tracts of interest. The proposed approach was applied and showed, for the first time, differences in local white matter fractional anisotropy based on in utero DTI of fetuses with congenital heart disease and age-matched healthy controls. This paper suggests the need for fetal-specific pipelines to be used for DTI-based group analysis involving fetal cohorts.