Davood Karimi

Davood Karimi, Caitlin K. Rollins, Clemente Velasco-Annis et al.

Automatic fetal brain tissue segmentation can enhance the quantitative assessment of brain development at this critical stage. Deep learning methods represent the state of the art in medical image segmentation and have also achieved impressive results in brain segmentation. However, effective training of a deep learning model to perform this task requires a large number of training images to represent the rapid development of the transient fetal brain structures. On the other hand, manual multi-label segmentation of a large number of 3D images is prohibitive. To address this challenge, we segmented 272 training images, covering 19-39 gestational weeks, using an automatic multi-atlas segmentation strategy based on deformable registration and probabilistic atlas fusion, and manually corrected large errors in those segmentations. Since this process generated a large training dataset with noisy segmentations, we developed a novel label smoothing procedure and a loss function to train a deep learning model with smoothed noisy segmentations. Our proposed methods properly account for the uncertainty in tissue boundaries. We evaluated our method on 23 manually-segmented test images of a separate set of fetuses. Results show that our method achieves an average Dice similarity coefficient of 0.893 and 0.916 for the transient structures of younger and older fetuses, respectively. Our method generated results that were significantly more accurate than several state-of-the-art methods including nnU-Net that achieved the closest results to our method. Our trained model can serve as a valuable tool to enhance the accuracy and reproducibility of fetal brain analysis in MRI.

Razieh Faghihpirayesh, Davood Karimi, Deniz Erdoğmuş et al.

Fetal brain extraction is a necessary first step in most computational fetal brain MRI pipelines. However, it has been a very challenging task due to non-standard fetal head pose, fetal movements during examination, and vastly heterogeneous appearance of the developing fetal brain and the neighboring fetal and maternal anatomy across various sequences and scanning conditions. Development of a machine learning method to effectively address this task requires a large and rich labeled dataset that has not been previously available. As a result, there is currently no method for accurate fetal brain extraction on various fetal MRI sequences. In this work, we first built a large annotated dataset of approximately 72,000 2D fetal brain MRI images. Our dataset covers the three common MRI sequences including T2-weighted, diffusion-weighted, and functional MRI acquired with different scanners. Moreover, it includes normal and pathological brains. Using this dataset, we developed and validated deep learning methods, by exploiting the power of the U-Net style architectures, the attention mechanism, multi-contrast feature learning, and data augmentation for fast, accurate, and generalizable automatic fetal brain extraction. Our approach leverages the rich information from multi-contrast (multi-sequence) fetal MRI data, enabling precise delineation of the fetal brain structures. Evaluations on independent test data show that our method achieves accurate brain extraction on heterogeneous test data acquired with different scanners, on pathological brains, and at various gestational stages. This robustness underscores the potential utility of our deep learning model for fetal brain imaging and image analysis.

Arvind Balachandrasekaran, Davood Karimi, Camilo Jaimes et al.

Quantitative Susceptibility Mapping is a parametric imaging technique to estimate the magnetic susceptibilities of biological tissues from MRI phase measurements. This problem of estimating the susceptibility map is ill posed. Regularized recovery approaches exploiting signal properties such as smoothness and sparsity improve reconstructions, but suffer from over-smoothing artifacts. Deep learning approaches have shown great potential and generate maps with reduced artifacts. However, for reasonable reconstructions and network generalization, they require numerous training datasets resulting in increased data acquisition time. To overcome this issue, we proposed a subject-specific, patch-based, unsupervised learning algorithm to estimate the susceptibility map. We make the problem well-posed by exploiting the redundancies across the patches of the map using a deep convolutional neural network. We formulated the recovery of the susceptibility map as a regularized optimization problem and adopted an alternating minimization strategy to solve it. We tested the algorithm on a 3D invivo dataset and, qualitatively and quantitatively, demonstrated improved reconstructions over competing methods.

Davood Karimi, Camilo Calixto, Haykel Snoussi et al.

Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain in-utero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain's cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.

Haykel Snoussi, Davood Karimi, Onur Afacan et al.

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 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 for model-free and 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.

Davood Karimi, Simon K. Warfield

\hspace{2mm} Diffusion-weighted magnetic resonance imaging (dMRI) of the brain offers unique capabilities including noninvasive probing of tissue microstructure and structural connectivity. It is widely used for clinical assessment of disease and injury, and for neuroscience research. Analyzing the dMRI data to extract useful information for medical and scientific purposes can be challenging. The dMRI measurements may suffer from strong noise and artifacts, and may exhibit high inter-session and inter-scanner variability in the data, as well as inter-subject heterogeneity in brain structure. Moreover, the relationship between measurements and the phenomena of interest can be highly complex. Recent years have witnessed increasing use of machine learning methods for dMRI analysis. This manuscript aims to assess these efforts, with a focus on methods that have addressed data preprocessing and harmonization, microstructure mapping, tractography, and white matter tract analysis. We study the main findings, strengths, and weaknesses of the existing methods and suggest topics for future research. We find that machine learning may be exceptionally suited to tackle some of the difficult tasks in dMRI analysis. However, for this to happen, several shortcomings of existing methods and critical unresolved issues need to be addressed. There is a pressing need to improve evaluation practices, to increase the availability of rich training datasets and validation benchmarks, as well as model generalizability, reliability, and explainability concerns.

Camilo Calixto, Camilo Jaimes, Matheus D. Soldatelli et al.

Diffusion-weighted Magnetic Resonance Imaging (dMRI) is increasingly used to study the fetal brain in utero. An important computation enabled by dMRI is streamline tractography, which has unique applications such as tract-specific analysis of the brain white matter and structural connectivity assessment. However, due to the low fetal dMRI data quality and the challenging nature of tractography, existing methods tend to produce highly inaccurate results. They generate many false streamlines while failing to reconstruct streamlines that constitute the major white matter tracts. In this paper, we advocate for anatomically constrained tractography based on an accurate segmentation of the fetal brain tissue directly in the dMRI space. We develop a deep learning method to compute the segmentation automatically. Experiments on independent test data show that this method can accurately segment the fetal brain tissue and drastically improve tractography results. It enables the reconstruction of highly curved tracts such as optic radiations. Importantly, our method infers the tissue segmentation and streamline propagation direction from a diffusion tensor fit to the dMRI data, making it applicable to routine fetal dMRI scans. The proposed method can lead to significant improvements in the accuracy and reproducibility of quantitative assessment of the fetal brain with dMRI.

Bo Li, Qi Zeng, Simon K. Warfield et al.

Diffusion MRI (dMRI) provides unique insights into fetal brain microstructure in utero. Longitudinal and cross-sectional fetal dMRI studies can reveal crucial neurodevelopmental changes but require precise spatial alignment across scans and subjects. This is challenging due to low data quality, rapid brain development, and limited anatomical landmarks. Existing registration methods, designed for high-quality adult data, struggle with these complexities. To address this, we introduce FetDTIAlign, a deep learning approach for fetal brain dMRI registration, enabling accurate affine and deformable alignment. FetDTIAlign features a dual-encoder architecture and iterative feature-based inference, reducing the impact of noise and low resolution. It optimizes network configurations and domain-specific features at each registration stage, enhancing both robustness and accuracy. We validated FetDTIAlign on data from 23 to 36 weeks gestation, covering 60 white matter tracts. It consistently outperformed two classical optimization-based methods and a deep learning pipeline, achieving superior anatomical correspondence. Further validation on external data from the Developing Human Connectome Project confirmed its generalizability across acquisition protocols. Our results demonstrate the feasibility of deep learning for fetal brain dMRI registration, providing a more accurate and reliable alternative to classical techniques. By enabling precise cross-subject and tract-specific analyses, FetDTIAlign supports new discoveries in early brain development.

Haykel Snoussi, Davood Karimi

Early and accurate assessment of brain microstructure using diffusion Magnetic Resonance Imaging (dMRI) is crucial for identifying neurodevelopmental disorders in neonates, but remains challenging due to low signal-to-noise ratio (SNR), motion artifacts, and ongoing myelination. In this study, we propose a rotationally equivariant Spherical Convolutional Neural Network (sCNN) framework tailored for neonatal dMRI. We predict the Fiber Orientation Distribution (FOD) from multi-shell dMRI signals acquired with a reduced set of gradient directions (30% of the full protocol), enabling faster and more cost-effective acquisitions. We train and evaluate the performance of our sCNN using real data from 43 neonatal dMRI datasets provided by the Developing Human Connectome Project (dHCP). Our results demonstrate that the sCNN achieves significantly lower mean squared error (MSE) and higher angular correlation coefficient (ACC) compared to a Multi-Layer Perceptron (MLP) baseline, indicating improved accuracy in FOD estimation. Furthermore, tractography results based on the sCNN-predicted FODs show improved anatomical plausibility, coverage, and coherence compared to those from the MLP. These findings highlight that sCNNs, with their inherent rotational equivariance, offer a promising approach for accurate and clinically efficient dMRI analysis, paving the way for improved diagnostic capabilities and characterization of early brain development.

Davood Karimi, Simon K. Warfield, Ali Gholipour

It is highly desirable to know how uncertain a model's predictions are, especially for models that are complex and hard to understand as in deep learning. Although there has been a growing interest in using deep learning methods in diffusion-weighted MRI, prior works have not addressed the issue of model uncertainty. Here, we propose a deep learning method to estimate the diffusion tensor and compute the estimation uncertainty. Data-dependent uncertainty is computed directly by the network and learned via loss attenuation. Model uncertainty is computed using Monte Carlo dropout. We also propose a new method for evaluating the quality of predicted uncertainties. We compare the new method with the standard least-squares tensor estimation and bootstrap-based uncertainty computation techniques. Our experiments show that when the number of measurements is small the deep learning method is more accurate and its uncertainty predictions are better calibrated than the standard methods. We show that the estimation uncertainties computed by the new method can highlight the model's biases, detect domain shift, and reflect the strength of noise in the measurements. Our study shows the importance and practical value of modeling prediction uncertainties in deep learning-based diffusion MRI analysis.

Davood Karimi, Rabab K. Ward

As the medical usage of computed tomography (CT) continues to grow, the radiation dose should remain at a low level to reduce the health risks. Therefore, there is an increasing need for algorithms that can reconstruct high-quality images from low-dose scans. In this regard, most of the recent studies have focused on iterative reconstruction algorithms, and little attention has been paid to restoration of the projection measurements, i.e., the sinogram. In this paper, we propose a novel sinogram interpolation algorithm. The proposed algorithm exploits the self-similarity and smoothness of the sinogram. Sinogram self-similarity is modeled in terms of the similarity of small blocks extracted from stacked projections. The smoothness is modeled via second-order total variation. Experiments with simulated and real CT data show that sinogram interpolation with the proposed algorithm leads to a substantial improvement in the quality of the reconstructed image, especially on low-dose scans. The proposed method can result in a significant reduction in the number of projection measurements. This will reduce the radiation dose and also the amount of data that need to be stored or transmitted, if the reconstruction is to be performed in a remote site.

Davood Karimi, Lana Vasung, Camilo Jaimes et al.

Multi-compartment modeling of diffusion-weighted magnetic resonance imaging measurements is necessary for accurate brain connectivity analysis. Existing methods for estimating the number and orientations of fascicles in an imaging voxel either depend on non-convex optimization techniques that are sensitive to initialization and measurement noise, or are prone to predicting spurious fascicles. In this paper, we propose a machine learning-based technique that can accurately estimate the number and orientations of fascicles in a voxel. Our method can be trained with either simulated or real diffusion-weighted imaging data. Our method estimates the angle to the closest fascicle for each direction in a set of discrete directions uniformly spread on the unit sphere. This information is then processed to extract the number and orientations of fascicles in a voxel. On realistic simulated phantom data with known ground truth, our method predicts the number and orientations of crossing fascicles more accurately than several existing methods. It also leads to more accurate tractography. On real data, our method is better than or compares favorably with standard methods in terms of robustness to measurement down-sampling and also in terms of expert quality assessment of tractography results.

Davood Karimi, Simon K. Warfield, Ali Gholipour

Transfer learning is widely used for training machine learning models. Here, we study the role of transfer learning for training fully convolutional networks (FCNs) for medical image segmentation. Our experiments show that although transfer learning reduces the training time on the target task, the improvement in segmentation accuracy is highly task/data-dependent. Larger improvements in accuracy are observed when the segmentation task is more challenging and the target training data is smaller. We observe that convolutional filters of an FCN change little during training for medical image segmentation, and still look random at convergence. We further show that quite accurate FCNs can be built by freezing the encoder section of the network at random values and only training the decoder section. At least for medical image segmentation, this finding challenges the common belief that the encoder section needs to learn data/task-specific representations. We examine the evolution of FCN representations to gain a better insight into the effects of transfer learning on the training dynamics. Our analysis shows that although FCNs trained via transfer learning learn different representations than FCNs trained with random initialization, the variability among FCNs trained via transfer learning can be as high as that among FCNs trained with random initialization. Moreover, feature reuse is not restricted to the early encoder layers; rather, it can be more significant in deeper layers. These findings offer new insights and suggest alternative ways of training FCNs for medical image segmentation.

Davood Karimi, Ali Gholipour

Convolutional Neural Networks (CNNs) have shown to be powerful medical image segmentation models. In this study, we address some of the main unresolved issues regarding these models. Specifically, training of these models on small medical image datasets is still challenging, with many studies promoting techniques such as transfer learning. Moreover, these models are infamous for producing over-confident predictions and for failing silently when presented with out-of-distribution (OOD) data at test time. In this paper, we advocate for multi-task learning, i.e., training a single model on several different datasets, spanning several different organs of interest and different imaging modalities. We show that not only a single CNN learns to automatically recognize the context and accurately segment the organ of interest in each context, but also that such a joint model often has more accurate and better-calibrated predictions than dedicated models trained separately on each dataset. Our experiments show that multi-task learning can outperform transfer learning in medical image segmentation tasks. For detecting OOD data, we propose a method based on spectral analysis of CNN feature maps. We show that different datasets, representing different imaging modalities and/or different organs of interest, have distinct spectral signatures, which can be used to identify whether or not a test image is similar to the images used to train a model. We show that this approach is far more accurate than OOD detection based on prediction uncertainty. The methods proposed in this paper contribute significantly to improving the accuracy and reliability of CNN-based medical image segmentation models.

Davood Karimi

Image models are central to all image processing tasks. The great advancements in digital image processing would not have been made possible without powerful models which, themselves, have evolved over time. In the past decade, patch-based models have emerged as one of the most effective models for natural images. Patch-based methods have outperformed other competing methods in many image processing tasks. These developments have come at a time when greater availability of powerful computational resources and growing concerns over the health risks of the ionizing radiation encourage research on image processing algorithms for computed tomography (CT). The goal of this paper is to explain the principles of patch-based methods and to review some of their recent applications in CT. We review the central concepts in patch-based image processing and explain some of the state-of-the-art algorithms, with a focus on aspects that are more relevant to CT. Then, we review some of the recent application of patch-based methods in CT.

Davood Karimi, Haoran Dou, Simon K. Warfield et al.

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.