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Ahtam, Banu, Susan Waisbren, Vera Anastasoaie, Gerard Berry, Matthew Brown, Stephanie Petrides, Onur Afacan, et al. 2020. “Identification of Neuronal Structures and Pathways Corresponding to Clinical Functioning in Galactosemia”. J Inherit Metab Dis 43 (6): 1205-18. https://doi.org/10.1002/jimd.12279.
Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.2 ± 5.47 years) received comprehensive neurological and neuropsychological evaluations, electroencephalogram (EEG) and magnetic resonance imaging (MRI). MRI data from nine healthy controls (mean age = 30.22 ± 3.52 years) were used for comparison measures. Galactosemia subjects experienced impaired memory, language processing, visual-motor skills, and increased anxiety. Neurological examinations revealed tremor and dysarthria in six subjects. In addition, there was ataxia in three subjects and six subjects had abnormal gait. Mean full scale IQ was 80.4 ± 17.3. EEG evaluations revealed right-sided abnormalities in five subjects and bilateral abnormalities in one subject. Compared to age- and gender-matched controls, subjects with galactosemia had reduced volume in left cerebellum white matter, bilateral putamen, and left superior temporal sulcus. Galactosemia patients also had lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls. Furthermore, there were significant correlations between neuropsychological test results and the T1 volume and diffusivity scalars. Our findings help to identify anatomic correlates to motor control, learning and memory, and language in subjects with galactosemia. The results from this preliminary assessment may provide insights into the pathophysiology of this inborn error of metabolism.

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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.
Snoussi, Haykel, Davood Karimi, Onur Afacan, Mustafa Utkur, and Ali Gholipour. (2025) 2025. “HAITCH: A Framework for Distortion and Motion Correction in Fetal Multi-Shell Diffusion-Weighted MRI.”. Imaging Neuroscience (Cambridge, Mass.) 3. https://doi.org/10.1162/imag_a_00490.
Publisher's Version
Publisher's Version

Diffusion magnetic resonance imaging (dMRI) is pivotal for probing the microstructure of the rapidly-developing fetal brain. However, fetal motion during scans and its interaction with magnetic field inhomogeneities result in artifacts and data scattering across spatial and angular domains. The effects of those artifacts are more pronounced in high-angular resolution fetal dMRI, where signal-to-noise ratio is very low. Those effects lead to biased estimates and compromise the consistency and reliability of dMRI analysis. This work presents High Angular resolution diffusion Imaging reconsTruction and Correction approacH (HAITCH), the first and the only publicly available tool to correct and reconstruct multi-shell high-angular resolution fetal dMRI data. HAITCH offers several technical advances that include a blip-reversed dual-echo acquisition for dynamic distortion correction, advanced motion correction formodel-freeand robust reconstruction, optimized multi-shell design for enhanced information capture and increased tolerance to motion, and outlier detection for improved reconstruction fidelity. The framework is open-source, flexible, and can be used to process any type of fetal dMRI data, including single-echo or single-shell acquisitions, but is most effective when used with multi-shell multi-echo fetal dMRI data that cannot be processed with any of the existing tools. Validation experiments on real fetal dMRI scans demonstrate significant improvements and accurate correction across diverse fetal ages and motion levels. HAITCH successfully removes artifacts and reconstructs high-fidelity fetal dMRI data suitable for advanced diffusion modeling, including fiber orientation distribution function estimation. These advancements pave the way for more reliable analysis of the fetal brain microstructure and tractography under challenging imaging conditions.

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Sui, Yao, Onur Afacan, Camilo Jaimes, Ali Gholipour, and Simon Warfield. (2021) 2021. “Gradient-Guided Isotropic MRI Reconstruction from Anisotropic Acquisitions”. IEEE Trans Comput Imaging 7: 1240-53. https://doi.org/10.1109/tci.2021.3128745.
The trade-off between image resolution, signal-to-noise ratio (SNR), and scan time in any magnetic resonance imaging (MRI) protocol is inevitable and unavoidable. Super-resolution reconstruction (SRR) has been shown effective in mitigating these factors, and thus, has become an important approach in addressing the current limitations of MRI. In this work, we developed a novel, image-based MRI SRR approach based on anisotropic acquisition schemes, which utilizes a new gradient guidance regularization method that guides the high-resolution (HR) reconstruction via a spatial gradient estimate. Further, we designed an analytical solution to propagate the spatial gradient fields from the low-resolution (LR) images to the HR image space and exploited these gradient fields over multiple scales with a dynamic update scheme for more accurate edge localization in the reconstruction. We also established a forward model of image formation and inverted it along with the proposed gradient guidance. The proposed SRR method allows subject motion between volumes and is able to incorporate various acquisition schemes where the LR images are acquired with arbitrary orientations and displacements, such as orthogonal and through-plane origin-shifted scans. We assessed our proposed approach on simulated data as well as on the data acquired on a Siemens 3T MRI scanner containing 45 MRI scans from 14 subjects. Our experimental results demonstrate that our approach achieved superior reconstructions compared to state-of-the-art methods, both in terms of local spatial smoothness and edge preservation, while, in parallel, at reduced, or at the same cost as scans delivered with direct HR acquisition.

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Ferris, Craig, Brain Smerkers, Praveen Kulkarni, Martha Caffrey, Onur Afacan, Steven Toddes, Tara Stolberg, and Marcelo Febo. (2011) 2011. “Functional Magnetic Resonance Imaging in Awake Animals”. Rev Neurosci 22 (6): 665-74. https://doi.org/10.1515/RNS.2011.050.
Awake animal imaging is becoming an important tool in behavioral neuroscience and preclinical drug discovery. Non-invasive ultra-high-field, functional magnetic resonance imaging (fMRI) provides a window to the mind, making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial resolution. In theory, changes in brain function, anatomy, and chemistry can be recorded in the same animal from early life into old age under stable or changing environmental conditions. This prospective capability of animal imaging to follow changes in brain neurobiology after genetic or environmental insult has great value to the fields of psychiatry and neurology and probably stands as the key advantage of MRI over other methods in the neuroscience toolbox. In addition, awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits or 'fingerprints' of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this review, we describe the methods used to image awake animals and the recent advances in the radiofrequency electronics, pulse sequences, and the development of 3D segmented atlases and software for image analysis. Results from pharmacological MRI studies and from studies using provocation paradigms to elicit emotional responses are provided as a small sample of the number of different applications possible with awake animal imaging.
Wallace, Tess, Onur Afacan, Camilo Jaimes, Joanne Rispoli, Kristina Pelkola, Monet Dugan, Tobias Kober, and Simon Warfield. 2021. “Free Induction Decay Navigator Motion Metrics for Prediction of Diagnostic Image Quality in Pediatric MRI”. Magn Reson Med 85 (6): 3169-81. https://doi.org/10.1002/mrm.28649.
PURPOSE: To investigate the ability of free induction decay navigator (FIDnav)-based motion monitoring to predict diagnostic utility and reduce the time and cost associated with acquiring diagnostically useful images in a pediatric patient cohort. METHODS: A study was carried out in 102 pediatric patients (aged 0-18 years) at 3T using a 32-channel head coil array. Subjects were scanned with an FID-navigated MPRAGE sequence and images were graded by two radiologists using a five-point scale to evaluate the impact of motion artifacts on diagnostic image quality. The correlation between image quality and four integrated FIDnav motion metrics was investigated, as well as the sensitivity and specificity of each FIDnav-based metric to detect different levels of motion corruption in the images. Potential time and cost savings were also assessed by retrospectively applying an optimal detection threshold to FIDnav motion scores. RESULTS: A total of 12% of images were rated as non-diagnostic, while a further 12% had compromised diagnostic value due to motion artifacts. FID-navigated metrics exhibited a moderately strong correlation with image grade (Spearman's rho ≥ 0.56). Integrating the cross-correlation between FIDnav signal vectors achieved the highest sensitivity and specificity for detecting non-diagnostic images, yielding total time savings of 7% across all scans. This corresponded to a financial benefit of $2080 in this study. CONCLUSIONS: Our results indicate that integrated motion metrics from FIDnavs embedded in structural MRI are a useful predictor of diagnostic image quality, which translates to substantial time and cost savings when applied to pediatric MRI examinations.
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.
Gholipour, Ali, Judith Estroff, Carol Barnewolt, Richard Robertson, Ellen Grant, Borjan Gagoski, Simon Warfield, et al. (2014) 2014. “Fetal MRI: A Technical Update With Educational Aspirations”. Concepts Magn Reson Part A Bridg Educ Res 43 (6): 237-66. https://doi.org/10.1002/cmr.a.21321.
Fetal magnetic resonance imaging (MRI) examinations have become well-established procedures at many institutions and can serve as useful adjuncts to ultrasound (US) exams when diagnostic doubts remain after US. Due to fetal motion, however, fetal MRI exams are challenging and require the MR scanner to be used in a somewhat different mode than that employed for more routine clinical studies. Herein we review the techniques most commonly used, and those that are available, for fetal MRI with an emphasis on the physics of the techniques and how to deploy them to improve success rates for fetal MRI exams. By far the most common technique employed is single-shot T2-weighted imaging due to its excellent tissue contrast and relative immunity to fetal motion. Despite the significant challenges involved, however, many of the other techniques commonly employed in conventional neuro- and body MRI such as T1 and T2*-weighted imaging, diffusion and perfusion weighted imaging, as well as spectroscopic methods remain of interest for fetal MR applications. An effort to understand the strengths and limitations of these basic methods within the context of fetal MRI is made in order to optimize their use and facilitate implementation of technical improvements for the further development of fetal MR imaging, both in acquisition and post-processing strategies.
Afacan, Onur, Ali Gholipour, Robert Mulkern, Carol Barnewolt, Judy Estroff, Susan Connolly, Richard Parad, Sigrid Bairdain, and Simon Warfield. 2016. “Fetal Lung Apparent Diffusion Coefficient Measurement Using Diffusion-Weighted MRI at 3 Tesla: Correlation With Gestational Age”. J Magn Reson Imaging 44 (6): 1650-55. https://doi.org/10.1002/jmri.25294.
PURPOSE: To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T). MATERIALS AND METHODS: Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated. RESULTS: When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks. CONCLUSION: We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655.
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.