Publications

2020

Karimi, Davood, Haoran Dou, Simon Warfield, and Ali Gholipour. 2020. “Deep learning with noisy labels: Exploring techniques and remedies in medical image analysis”. Med Image Anal 65: 101759. https://doi.org/10.1016/j.media.2020.101759.
Supervised training of deep learning models requires large labeled datasets. There is a growing interest in obtaining such datasets for medical image analysis applications. However, the impact of label noise has not received sufficient attention. Recent studies have shown that label noise can significantly impact the performance of deep learning models in many machine learning and computer vision applications. This is especially concerning for medical applications, where datasets are typically small, labeling requires domain expertise and suffers from high inter- and intra-observer variability, and erroneous predictions may influence decisions that directly impact human health. In this paper, we first review the state-of-the-art in handling label noise in deep learning. Then, we review studies that have dealt with label noise in deep learning for medical image analysis. Our review shows that recent progress on handling label noise in deep learning has gone largely unnoticed by the medical image analysis community. To help achieve a better understanding of the extent of the problem and its potential remedies, we conducted experiments with three medical imaging datasets with different types of label noise, where we investigated several existing strategies and developed new methods to combat the negative effect of label noise. Based on the results of these experiments and our review of the literature, we have made recommendations on methods that can be used to alleviate the effects of different types of label noise on deep models trained for medical image analysis. We hope that this article helps the medical image analysis researchers and developers in choosing and devising new techniques that effectively handle label noise in deep learning.
Vasung, Lana, Caitlin Rollins, Clemente Velasco-Annis, Hyuk Jin Yun, Jennings Zhang, Simon Warfield, Henry Feldman, Ali Gholipour, and Ellen Grant. 2020. “Spatiotemporal Differences in the Regional Cortical Plate and Subplate Volume Growth during Fetal Development”. Cereb Cortex 30 (8): 4438-53. https://doi.org/10.1093/cercor/bhaa033.
The regional specification of the cerebral cortex can be described by protomap and protocortex hypotheses. The protomap hypothesis suggests that the regional destiny of cortical neurons and the relative size of the cortical area are genetically determined early during embryonic development. The protocortex hypothesis suggests that the regional growth rate is predominantly shaped by external influences. In order to determine regional volumes of cortical compartments (cortical plate (CP) or subplate (SP)) and estimate their growth rates, we acquired T2-weighted in utero MRIs of 40 healthy fetuses and grouped them into early (31.6 GW) prenatal periods. MRIs were segmented into CP and SP and further parcellated into 22 gyral regions. No significant difference was found between periods in regional volume fractions of the CP or SP. However, during the early and mid-prenatal periods, we found significant differences in relative growth rates (% increase per GW) between regions of cortical compartments. Thus, the relative size of these regions are most likely conserved and determined early during development whereas more subtle growth differences between regions are fine-tuned later, during periods of peak thalamocortical growth. This is in agreement with both the protomap and protocortex hypothesis.
Afacan, Onur, Scott Hoge, Tess Wallace, Ali Gholipour, Sila Kurugol, and Simon Warfield. (2020) 2020. “Simultaneous Motion and Distortion Correction Using Dual-Echo Diffusion-Weighted MRI”. J Neuroimaging 30 (3): 276-85. https://doi.org/10.1111/jon.12708.
BACKGROUND AND PURPOSE: Geometric distortions resulting from large pose changes reduce the accuracy of motion measurements and interfere with the ability to generate artifact-free information. Our goal is to develop an algorithm and pulse sequence to enable motion-compensated, geometric distortion compensated diffusion-weighted MRI, and to evaluate its efficacy in correcting for the field inhomogeneity and position changes, induced by large and frequent head motions. METHODS: Dual echo planar imaging (EPI) with a blip-reversed phase encoding distortion correction technique was evaluated in five volunteers in two separate experiments and compared with static field map distortion correction. In the first experiment, dual-echo EPI images were acquired in two head positions designed to induce a large field inhomogeneity change. A field map and a distortion-free structural image were acquired at each position to assess the ability of dual-echo EPI to generate reliable field maps and enable geometric distortion correction in both positions. In the second experiment, volunteers were asked to move to multiple random positions during a diffusion scan. Images were reconstructed using the dual-echo correction and a slice-to-volume registration (SVR) registration algorithm. The accuracy of SVR motion estimates was compared to externally measured ground truth motion parameters. RESULTS: Our results show that dual-echo EPI can produce slice-level field maps with comparable quality to field maps generated by the reference gold standard method. We also show that slice-level distortion correction improves the accuracy of SVR algorithms as slices acquired at different orientations have different levels of distortion, which can create errors in the registration process. CONCLUSIONS: Dual-echo acquisitions with blip-reversed phase encoding can be used to generate slice-level distortion-free images, which is critical for motion-robust slice to volume registration. The distortion corrected images not only result in better motion estimates, but they also enable a more accurate final diffusion image reconstruction.
Jaimes, Camilo, Fedel Machado-Rivas, Onur Afacan, Shadab Khan, Bahram Marami, Cynthia Ortinau, Caitlin Rollins, Clemente Velasco-Annis, Simon Warfield, and Ali Gholipour. 2020. “In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester”. Hum Brain Mapp 41 (12): 3177-85. https://doi.org/10.1002/hbm.25006.
The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion-tracked slice-to-volume registration (MT-SVR) method, we aimed to quantify tract-specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2-8) diffusion scans of the fetal head (1-2 b = 0 s/mm images and 12 diffusion-sensitized images at b = 500 s/mm ). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT-SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto-occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract-specific, GA-related microstructural changes of the developing white matter in human fetal brain.
Vasung, Lana, Caitlin Rollins, Hyuk Jin Yun, Clemente Velasco-Annis, Jennings Zhang, Konrad Wagstyl, Alan Evans, et al. 2020. “Quantitative In vivo MRI Assessment of Structural Asymmetries and Sexual Dimorphism of Transient Fetal Compartments in the Human Brain”. Cereb Cortex 30 (3): 1752-67. https://doi.org/10.1093/cercor/bhz200.
Structural asymmetries and sexual dimorphism of the human cerebral cortex have been identified in newborns, infants, children, adolescents, and adults. Some of these findings were linked with cognitive and neuropsychiatric disorders, which have roots in altered prenatal brain development. However, little is known about structural asymmetries or sexual dimorphism of transient fetal compartments that arise in utero. Thus, we aimed to identify structural asymmetries and sexual dimorphism in the volume of transient fetal compartments (cortical plate [CP] and subplate [SP]) across 22 regions. For this purpose, we used in vivo structural T2-weighted MRIs of 42 healthy fetuses (16.43-36.86 gestational weeks old, 15 females). We found significant leftward asymmetry in the volume of the CP and SP in the inferior frontal gyrus. The orbitofrontal cortex showed significant rightward asymmetry in the volume of CP merged with SP. Males had significantly larger volumes in regions belonging to limbic, occipital, and frontal lobes, which were driven by a significantly larger SP. Lastly, we did not observe sexual dimorphism in the growth trajectories of the CP or SP. In conclusion, these results support the hypothesis that structural asymmetries and sexual dimorphism in relative volumes of cortical regions are present during prenatal brain development.
Singh, Ayush, Seyed Sadegh Mohseni Salehi, and Ali Gholipour. 2020. “Deep Predictive Motion Tracking in Magnetic Resonance Imaging: Application to Fetal Imaging”. IEEE Trans Med Imaging PP. https://doi.org/10.1109/TMI.2020.2998600.
Fetal magnetic resonance imaging (MRI) is challenged by uncontrollable, large, and irregular fetal movements. It is, therefore, performed through visual monitoring of fetal motion and repeated acquisitions to ensure diagnostic-quality images are acquired. Nevertheless, visual monitoring of fetal motion based on displayed slices, and navigation at the level of stacks-of-slices is inefficient. The current process is highly operator-dependent, increases scanner usage and cost, and significantly increases the length of fetal MRI scans which makes them hard to tolerate for pregnant women. To help build automatic MRI motion tracking and navigation systems to overcome the limitations of the current process and improve fetal imaging, we have developed a new realtime image-based motion tracking method based on deep learning that learns to predict fetal motion directly from acquired images. Our method is based on a recurrent neural network, composed of spatial and temporal encoder-decoders, that infers motion parameters from anatomical features extracted from sequences of acquired slices. We compared our trained network on heldout test sets (including data with different characteristics, e.g. different fetuses scanned at different ages, and motion trajectories recorded from volunteer subjects) with networks designed for estimation as well as methods adopted to make predictions. The results show that our method outperformed alternative techniques, and achieved real-time performance with average errors of 3.5 and 8 degrees for the estimation and prediction tasks, respectively. Our real-time deep predictive motion tracking technique can be used to assess fetal movements, to guide slice acquisitions, and to build navigation systems for fetal MRI.
Jaimes, Rofeberg, Stopp, Ortinau, Gholipour, Friedman, Tworetzky, et al. 2020. “Association of Isolated Congenital Heart Disease with Fetal Brain Maturation”. AJNR Am J Neuroradiol. https://doi.org/10.3174/ajnr.A6635.
BACKGROUND AND PURPOSE: Brain MRI of newborns with congenital heart disease show signs of immaturity relative to healthy controls. Our aim was to determine whether the semiquantitative fetal total maturation score can detect abnormalities in brain maturation in fetuses with congenital heart disease in the second and third trimesters. MATERIALS AND METHODS: We analyzed data from a prospective study of fetuses with and without congenital heart disease who underwent fetal MR imaging at 25-35 weeks' gestation. Two independent neuroradiologists blinded to the clinical data reviewed and scored all images using the fetal total maturation score. Interrater reliability was evaluated by the intraclass correlation coefficient using the individual reader scores, which were also used to calculate an average score for each subject. Comparisons of the average and individual reader scores between affected and control fetuses and relationships with clinical variables were evaluated using multivariable linear regression. RESULTS: Data from 69 subjects (48 cardiac, 21 controls) were included. High concordance was observed between readers with an intraclass correlation coefficient of 0.98 (95% CI, 0.97-0.99). The affected group had significantly lower fetal total maturation scores than the control group (-estimate, -0.9 [95% CI, -1.5 to -0.4], = .002), adjusting for gestational age and sex. Averaged fetal total maturation, germinal matrix, myelination, and superior temporal sulcus scores were significantly delayed in fetuses with congenital heart disease versus controls ( 

2019

Sui, Yao, Onur Afacan, Ali Gholipour, and Simon Warfield. (2019) 2019. “Isotropic MRI Super-Resolution Reconstruction with Multi-scale Gradient Field Prior”. Med Image Comput Comput Assist Interv 11766: 3-11. https://doi.org/10.1007/978-3-030-32248-9_1.
In this work, we proposed a novel image-based MRI super-resolution reconstruction (SRR) approach based on anisotropic acquisition schemes. We achieved superior reconstruction to state-of-the-art work by introducing a new multi-scale gradient field prior that guides the reconstruction of the high-resolution (HR) image. The prior improves both spatial smoothness and edge preservation. The inverse of the forward model of image formation is used to propagate the gradient guidance from the low-resolution (LR) images to the HR image space. The gradient fields over multiple scales were exploited for more accurate edge localization in the reconstruction. The proposed SRR allows inter-volume motion during the MRI scans and can incorporate with the LR images with arbitrary orientations and displacements in the frequency space, such as orthogonal and origin-shifted scans. The proposed approach was evaluated on the synthetic data as well as the data acquired on a Siemens 3T MRI scanner containing 45 MRI scans from 14 subjects. The evaluation results demonstrate that our proposed prior leads to improved SRR as compared to state-of-the-art priors, and that the proposed SRR obtains better results at lower or the same cost in scan time than direct HR acquisition. In particular, the anatomical structures of hippocampus can be clearly shown in our reconstructed images. This is a significant improvement for the in vivo studies of the hippocampus.
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.