In fetal Magnetic Resonance Imaging, Super Resolution Reconstruction (SRR) algorithms are becoming popular tools to obtain high-resolution 3D volume reconstructions from low-resolution stacks of 2D slices, acquired at different orientations. To be effective, these algorithms often require accurate segmentation of the region of interest, such as the fetal brain in suspected pathological cases. In the case of Spina Bifida, Ebner, Wang et al. (NeuroImage, 2020) combined their SRR algorithm with a 2-step segmentation pipeline (2D localisation followed by a 2D segmentation network). However, if the localisation step fails, the second network is not able to recover a correct brain mask, thus requiring manual corrections for an effective SRR. In this work, we aim at improving the fetal brain segmentation for SRR in Spina Bifida. We hypothesise that a well-trained single-step UNet can achieve accurate performance, avoiding the need of a 2-step approach. We propose a new tool for fetal brain segmentation called MONAIfbs, which takes advantage of the Medical Open Network for Artificial Intelligence (MONAI) framework. Our network is based on the dynamic UNet (dynUNet), an adaptation of the nnU-Net framework. When compared to the original 2-step approach proposed in Ebner-Wang, and the same Ebner-Wang approach retrained with the expanded dataset available for this work, the dynUNet showed to achieve higher performance using a single step only. It also showed to reduce the number of outliers, as only 28 stacks obtained Dice score less than 0.9, compared to 68 for Ebner-Wang and 53 Ebner-Wang expanded. The proposed dynUNet model thus provides an improvement of the state-of-the-art fetal brain segmentation techniques, reducing the need for manual correction in automated SRR pipelines. Our code and our trained model are made publicly available at https://github.com/gift-surg/MONAIfbs.
Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.
Segmentation of the developing fetal brain is an important step in quantitative analyses. However, manual segmentation is a very time-consuming task which is prone to error and must be completed by highly specialized indi-viduals. Super-resolution reconstruction of fetal MRI has become standard for processing such data as it improves image quality and resolution. However, dif-ferent pipelines result in slightly different outputs, further complicating the gen-eralization of segmentation methods aiming to segment super-resolution data. Therefore, we propose using transfer learning with noisy multi-class labels to automatically segment high resolution fetal brain MRIs using a single set of seg-mentations created with one reconstruction method and tested for generalizability across other reconstruction methods. Our results show that the network can auto-matically segment fetal brain reconstructions into 7 different tissue types, regard-less of reconstruction method used. Transfer learning offers some advantages when compared to training without pre-initialized weights, but the network trained on clean labels had more accurate segmentations overall. No additional manual segmentations were required. Therefore, the proposed network has the potential to eliminate the need for manual segmentations needed in quantitative analyses of the fetal brain independent of reconstruction method used, offering an unbiased way to quantify normal and pathological neurodevelopment.
Objective: Hydrocephalus is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid (CSF) in the brain. Segmentation of brain imagery into brain tissue and CSF (before and after surgery, i.e. pre-op vs. postop) plays a crucial role in evaluating surgical treatment. Segmentation of pre-op images is often a relatively straightforward problem and has been well researched. However, segmenting post-operative (post-op) computational tomographic (CT)-scans becomes more challenging due to distorted anatomy and subdural hematoma collections pressing on the brain. Most intensity and feature based segmentation methods fail to separate subdurals from brain and CSF as subdural geometry varies greatly across different patients and their intensity varies with time. We combat this problem by a learning approach that treats segmentation as supervised classification at the pixel level, i.e. a training set of CT scans with labeled pixel identities is employed. Methods: Our contributions include: 1.) a dictionary learning framework that learns class (segment) specific dictionaries that can efficiently represent test samples from the same class while poorly represent corresponding samples from other classes, 2.) quantification of associated computation and memory footprint, and 3.) a customized training and test procedure for segmenting post-op hydrocephalic CT images. Results: Experiments performed on infant CT brain images acquired from the CURE Children's Hospital of Uganda reveal the success of our method against the state-of-the-art alternatives. We also demonstrate that the proposed algorithm is computationally less burdensome and exhibits a graceful degradation against number of training samples, enhancing its deployment potential.
We propose a client-server system which allows for the analysis of multi-centric medical images while preserving patient identity. In our approach, the client protects the patient identity by applying a pseudo-random non-linear deformation to the input image. This results into a proxy image which is sent to the server for processing. The server then returns back the deformed processed image which the client reverts to a canonical form. Our system has three components: 1) a flow-field generator which produces a pseudo-random deformation function, 2) a Siamese discriminator that learns the patient identity from the processed image, 3) a medical image processing network that analyzes the content of the proxy images. The system is trained end-to-end in an adversarial manner. By fooling the discriminator, the flow-field generator learns to produce a bi-directional non-linear deformation which allows to remove and recover the identity of the subject from both the input image and output result. After end-to-end training, the flow-field generator is deployed on the client side and the segmentation network is deployed on the server side. The proposed method is validated on the task of MRI brain segmentation using images from two different datasets. Results show that the segmentation accuracy of our method is similar to a system trained on non-encoded images, while considerably reducing the ability to recover subject identity.
It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open databases of segmented fetal brains. Here we introduce a publicly available database of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the database for the development of automatic algorithms.
In this paper we propose a novel method for the segmentation of longitudinal brain MRI scans of patients suffering from Multiple Sclerosis. The method builds upon an existing cross-sectional method for simultaneous whole-brain and lesion segmentation, introducing subject-specific latent variables to encourage temporal consistency between longitudinal scans. It is very generally applicable, as it does not make any prior assumptions on the scanner, the MRI protocol, or the number and timing of longitudinal follow-up scans. Preliminary experiments on three longitudinal datasets indicate that the proposed method produces more reliable segmentations and detects disease effects better than the cross-sectional method it is based upon.
For semantic segmentation, label probabilities are often uncalibrated as they are typically only the by-product of a segmentation task. Intersection over Union (IoU) and Dice score are often used as criteria for segmentation success, while metrics related to label probabilities are not often explored. However, probability calibration approaches have been studied, which match probability outputs with experimentally observed errors. These approaches mainly focus on classification tasks, but not on semantic segmentation. Thus, we propose a learning-based calibration method that focuses on multi-label semantic segmentation. Specifically, we adopt a convolutional neural network to predict local temperature values for probability calibration. One advantage of our approach is that it does not change prediction accuracy, hence allowing for calibration as a post-processing step. Experiments on the COCO, CamVid, and LPBA40 datasets demonstrate improved calibration performance for a range of different metrics. We also demonstrate the good performance of our method for multi-atlas brain segmentation from magnetic resonance images.
Purpose: To implement a brain segmentation pipeline based on convolutional neural networks, which rapidly segments 3D volumes into 27 anatomical structures. To provide an extensive, comparative study of segmentation performance on various contrasts of magnetic resonance imaging (MRI) and computed tomography (CT) scans. Methods: Deep convolutional neural networks are trained to segment 3D MRI (MPRAGE, DWI, FLAIR) and CT scans. A large database of in total 851 MRI/CT scans is used for neural network training. Training labels are obtained on the MPRAGE contrast and coregistered to the other imaging modalities. The segmentation quality is quantified using the Dice metric for a total of 27 anatomical structures. Dropout sampling is implemented to identify corrupted input scans or low-quality segmentations. Full segmentation of 3D volumes with more than 2 million voxels is obtained in less than 1s of processing time on a graphical processing unit. Results: The best average Dice score is found on $T_1$-weighted MPRAGE ($85.3\pm4.6\,\%$). However, for FLAIR ($80.0\pm7.1\,\%$), DWI ($78.2\pm7.9\,\%$) and CT ($79.1\pm 7.9\,\%$), good-quality segmentation is feasible for most anatomical structures. Corrupted input volumes or low-quality segmentations can be detected using dropout sampling. Conclusion: The flexibility and performance of deep convolutional neural networks enables the direct, real-time segmentation of FLAIR, DWI and CT scans without requiring $T_1$-weighted scans.
To better understand early brain growth patterns in health and disorder, it is critical to accurately segment infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). Deep learning-based methods have achieved state-of-the-art performance; however, one of major limitations is that the learning-based methods may suffer from the multi-site issue, that is, the models trained on a dataset from one site may not be applicable to the datasets acquired from other sites with different imaging protocols/scanners. To promote methodological development in the community, iSeg-2019 challenge (http://iseg2019.web.unc.edu) provides a set of 6-month infant subjects from multiple sites with different protocols/scanners for the participating methods. Training/validation subjects are from UNC (MAP) and testing subjects are from UNC/UMN (BCP), Stanford University, and Emory University. By the time of writing, there are 30 automatic segmentation methods participating in iSeg-2019. We review the 8 top-ranked teams by detailing their pipelines/implementations, presenting experimental results and evaluating performance in terms of the whole brain, regions of interest, and gyral landmark curves. We also discuss their limitations and possible future directions for the multi-site issue. We hope that the multi-site dataset in iSeg-2019 and this review article will attract more researchers on the multi-site issue.
Segmentation of the fetal brain from stacks of motion-corrupted fetal MRI slices is important for motion correction and high-resolution volume reconstruction. Although Convolutional Neural Networks (CNNs) have been widely used for automatic segmentation of the fetal brain, their results may still benefit from interactive refinement for challenging slices. To improve the efficiency of interactive refinement process, we propose an Uncertainty-Guided Interactive Refinement (UGIR) framework. We first propose a grouped convolution-based CNN to obtain multiple automatic segmentation predictions with uncertainty estimation in a single forward pass, then guide the user to provide interactions only in a subset of slices with the highest uncertainty. A novel interactive level set method is also proposed to obtain a refined result given the initial segmentation and user interactions. Experimental results show that: (1) our proposed CNN obtains uncertainty estimation in real time which correlates well with mis-segmentations, (2) the proposed interactive level set is effective and efficient for refinement, (3) UGIR obtains accurate refinement results with around 30% improvement of efficiency by using uncertainty to guide user interactions. Our code is available online.
Brain extraction or skull stripping of magnetic resonance images (MRI) is an essential step in neuroimaging studies, the accuracy of which can severely affect subsequent image processing procedures. Current automatic brain extraction methods demonstrate good results on human brains, but are often far from satisfactory on nonhuman primates, which are a necessary part of neuroscience research. To overcome the challenges of brain extraction in nonhuman primates, we propose a fully-automated brain extraction pipeline combining deep Bayesian convolutional neural network (CNN) and fully connected three-dimensional (3D) conditional random field (CRF). The deep Bayesian CNN, Bayesian SegNet, is used as the core segmentation engine. As a probabilistic network, it is not only able to perform accurate high-resolution pixel-wise brain segmentation, but also capable of measuring the model uncertainty by Monte Carlo sampling with dropout in the testing stage. Then, fully connected 3D CRF is used to refine the probability result from Bayesian SegNet in the whole 3D context of the brain volume. The proposed method was evaluated with a manually brain-extracted dataset comprising T1w images of 100 nonhuman primates. Our method outperforms six popular publicly available brain extraction packages and three well-established deep learning based methods with a mean Dice coefficient of 0.985 and a mean average symmetric surface distance of 0.220 mm. A better performance against all the compared methods was verified by statistical tests (all p-values<10-4, two-sided, Bonferroni corrected). The maximum uncertainty of the model on nonhuman primate brain extraction has a mean value of 0.116 across all the 100 subjects...
Affine registration of one or several brain image(s) onto a common reference space is a necessary prerequisite for many image processing tasks, such as brain segmentation or functional analysis. Manual assessment of registration quality is a tedious and time-consuming task, especially in studies comprising a large amount of data. An automated and reliable quality control (QC) becomes mandatory. Moreover, the computation time of the QC must be also compatible with the processing of massive datasets. Therefore, an automated deep neural network approaches appear as a method of choice to automatically assess registration quality. In the current study, a compact 3D convolutional neural network (CNN), referred to as RegQCNET, is introduced to quantitatively predict the amplitude of an affine registration mismatch between a registered image and a reference template. This quantitative estimation of registration error is expressed using metric unit system. Therefore, a meaningful task-specific threshold can be manually or automatically defined in order to distinguish usable and non-usable images. The robustness of the proposed RegQCNET is first analyzed on lifespan brain images undergoing various simulated spatial transformations and intensity variations between training and testing. Secondly, the potential of RegQCNET to classify images as usable or non-usable is evaluated using both manual and automatic thresholds. During our experiments, automatic thresholds are estimated using several computer-assisted classification models through cross-validation. To this end we used expert's visual quality control estimated on a lifespan cohort of 3953 brains. Finally, the RegQCNET accuracy is compared to usual image features. Results show that the proposed deep learning QC is robust, fast and accurate to estimate affine registration error in processing pipeline.
Here we present a method for the simultaneous segmentation of white matter lesions and normal-appearing neuroanatomical structures from multi-contrast brain MRI scans of multiple sclerosis patients. The method integrates a novel model for white matter lesions into a previously validated generative model for whole-brain segmentation. By using separate models for the shape of anatomical structures and their appearance in MRI, the algorithm can adapt to data acquired with different scanners and imaging protocols without retraining. We validate the method using four disparate datasets, showing robust performance in white matter lesion segmentation while simultaneously segmenting dozens of other brain structures. We further demonstrate that the contrast-adaptive method can also be safely applied to MRI scans of healthy controls, and replicate previously documented atrophy patterns in deep gray matter structures in MS. The algorithm is publicly available as part of the open-source neuroimaging package FreeSurfer.
The ability of neural networks to continuously learn and adapt to new tasks while retaining prior knowledge is crucial for many applications. However, current neural networks tend to forget previously learned tasks when trained on new ones, i.e., they suffer from Catastrophic Forgetting (CF). The objective of Continual Learning (CL) is to alleviate this problem, which is particularly relevant for medical applications, where it may not be feasible to store and access previously used sensitive patient data. In this work, we propose a Continual Learning approach for brain segmentation, where a single network is consecutively trained on samples from different domains. We build upon an importance driven approach and adapt it for medical image segmentation. Particularly, we introduce learning rate regularization to prevent the loss of the network's knowledge. Our results demonstrate that directly restricting the adaptation of important network parameters clearly reduces Catastrophic Forgetting for segmentation across domains.
Automated brain structure segmentation is important to many clinical quantitative analysis and diagnoses. In this work, we introduce MixNet, a 2D semantic-wise deep convolutional neural network to segment brain structure in multi-modality MRI images. The network is composed of our modified deep residual learning units. In the unit, we replace the traditional convolution layer with the dilated convolutional layer, which avoids the use of pooling layers and deconvolutional layers, reducing the number of network parameters. Final predictions are made by aggregating information from multiple scales and modalities. A pyramid pooling module is used to capture spatial information of the anatomical structures at the output end. In addition, we test three architectures (MixNetv1, MixNetv2 and MixNetv3) which fuse the modalities differently to see the effect on the results. Our network achieves the state-of-the-art performance. MixNetv2 was submitted to the MRBrainS challenge at MICCAI 2018 and won the 3rd place in the 3-label task. On the MRBrainS2018 dataset, which includes subjects with a variety of pathologies, the overall DSC (Dice Coefficient) of 84.7% (gray matter), 87.3% (white matter) and 83.4% (cerebrospinal fluid) were obtained with only 7 subjects as training data.
Medical image segmentation is one of the major challenges addressed by machine learning methods. Yet, deep learning methods profoundly depend on a large amount of annotated data, which is time-consuming and costly. Though, semi-supervised learning methods approach this problem by leveraging an abundant amount of unlabeled data along with a small amount of labeled data in the training process. Recently, MixUp regularizer has been successfully introduced to semi-supervised learning methods showing superior performance. MixUp augments the model with new data points through linear interpolation of the data at the input space. We argue that this option is limited. Instead, we propose ROAM, a RandOm lAyer Mixup, which encourages the network to be less confident for interpolated data points at randomly selected space. ROAM generates more data points that have never seen before, and hence it avoids over-fitting and enhances the generalization ability. We conduct extensive experiments to validate our method on three publicly available datasets on whole-brain image segmentation. ROAM achieves state-of-the-art (SOTA) results in fully supervised (89.5%) and semi-supervised (87.0%) settings with a relative improvement of up to 2.40% and 16.50%, respectively for the whole-brain segmentation.
We present a deep learning strategy that enables, for the first time, contrast-agnostic semantic segmentation of completely unpreprocessed brain MRI scans, without requiring additional training or fine-tuning for new modalities. Classical Bayesian methods address this segmentation problem with unsupervised intensity models, but require significant computational resources. In contrast, learning-based methods can be fast at test time, but are sensitive to the data available at training. Our proposed learning method, SynthSeg, leverages a set of training segmentations (no intensity images required) to generate synthetic sample images of widely varying contrasts on the fly during training. These samples are produced using the generative model of the classical Bayesian segmentation framework, with randomly sampled parameters for appearance, deformation, noise, and bias field. Because each mini-batch has a different synthetic contrast, the final network is not biased towards any MRI contrast. We comprehensively evaluate our approach on four datasets comprising over 1,000 subjects and four types of MR contrast. The results show that our approach successfully segments every contrast in the data, performing slightly better than classical Bayesian segmentation, and three orders of magnitude faster. Moreover, even within the same type of MRI contrast, our strategy generalizes significantly better across datasets, compared to training using real images. Finally, we find that synthesizing a broad range of contrasts, even if unrealistic, increases the generalization of the neural network. Our code and model are open source at https://github.com/BBillot/SynthSeg.
Glioma is a common type of brain tumor, and accurate detection of it plays a vital role in the diagnosis and treatment process. Despite advances in medical image analyzing, accurate tumor segmentation in brain magnetic resonance (MR) images remains a challenge due to variations in tumor texture, position, and shape. In this paper, we propose a fast, automated method, with light computational complexity, to find the smallest bounding box around the tumor region. This region-of-interest can be used as a preprocessing step in training networks for subregion tumor segmentation. By adopting the outputs of this algorithm, redundant information is removed; hence the network can focus on learning notable features related to subregions' classes. The proposed method has six main stages, in which the brain segmentation is the most vital step. Expectation-maximization (EM) and K-means algorithms are used for brain segmentation. The proposed method is evaluated on the BraTS 2015 dataset, and the average gained DICE score is 0.73, which is an acceptable result for this application.
Fully Convolutional Neural Networks (F-CNNs) achieve state-of-the-art performance for segmentation tasks in computer vision and medical imaging. Recently, computational blocks termed squeeze and excitation (SE) have been introduced to recalibrate F-CNN feature maps both channel- and spatial-wise, boosting segmentation performance while only minimally increasing the model complexity. So far, the development of SE blocks has focused on 2D architectures. For volumetric medical images, however, 3D F-CNNs are a natural choice. In this article, we extend existing 2D recalibration methods to 3D and propose a generic compress-process-recalibrate pipeline for easy comparison of such blocks. We further introduce Project & Excite (PE) modules, customized for 3D networks. In contrast to existing modules, Project \& Excite does not perform global average pooling but compresses feature maps along different spatial dimensions of the tensor separately to retain more spatial information that is subsequently used in the excitation step. We evaluate the modules on two challenging tasks, whole-brain segmentation of MRI scans and whole-body segmentation of CT scans. We demonstrate that PE modules can be easily integrated into 3D F-CNNs, boosting performance up to 0.3 in Dice Score and outperforming 3D extensions of other recalibration blocks, while only marginally increasing the model complexity. Our code is publicly available on https://github.com/ai-med/squeeze_and_excitation .