3D Brainformer: 3D Fusion Transformer for Brain Tumor Segmentation

Magnetic resonance imaging (MRI) is critically important for brain mapping in both scientific research and clinical studies. Precise segmentation of brain tumors facilitates clinical diagnosis, evaluations, and surgical planning. Deep learning has recently emerged to improve brain tumor segmentation and achieved impressive results. Convolutional architectures are widely used to implement those neural networks. By the nature of limited receptive fields, however, those architectures are subject to representing long-range spatial dependencies of the voxel intensities in MRI images. Transformers have been leveraged recently to address the above limitations of convolutional networks. Unfortunately, the majority of current Transformers-based methods in segmentation are performed with 2D MRI slices, instead of 3D volumes. Moreover, it is difficult to incorporate the structures between layers because each head is calculated independently in the Multi-Head Self-Attention mechanism (MHSA). In this work, we proposed a 3D Transformer-based segmentation approach. We developed a Fusion-Head Self-Attention mechanism (FHSA) to combine each attention head through attention logic and weight mapping, for the exploration of the long-range spatial dependencies in 3D MRI images. We implemented a plug-and-play self-attention module, named the Infinite Deformable Fusion Transformer Module (IDFTM), to extract features on any deformable feature maps. We applied our approach to the task of brain tumor segmentation, and assessed it on the public BRATS datasets. The experimental results demonstrated that our proposed approach achieved superior performance, in comparison to several state-of-the-art segmentation methods.

Atlas-powered deep learning (ADL) -- application to diffusion weighted MRI

Deep learning has a great potential for estimating biomarkers in diffusion weighted magnetic resonance imaging (dMRI). Atlases, on the other hand, are a unique tool for modeling the spatio-temporal variability of biomarkers. In this paper, we propose the first framework to exploit both deep learning and atlases for biomarker estimation in dMRI. Our framework relies on non-linear diffusion tensor registration to compute biomarker atlases and to estimate atlas reliability maps. We also use nonlinear tensor registration to align the atlas to a subject and to estimate the error of this alignment. We use the biomarker atlas, atlas reliability map, and alignment error map, in addition to the dMRI signal, as inputs to a deep learning model for biomarker estimation. We use our framework to estimate fractional anisotropy and neurite orientation dispersion from down-sampled dMRI data on a test cohort of 70 newborn subjects. Results show that our method significantly outperforms standard estimation methods as well as recent deep learning techniques. Our method is also more robust to stronger measurement down-sampling factors. Our study shows that the advantages of deep learning and atlases can be synergistically combined to achieve unprecedented accuracy in biomarker estimation from dMRI data.

Deep Learning Framework for Real-time Fetal Brain Segmentation in MRI

Fetal brain segmentation is an important first step for slice-level motion correction and slice-to-volume reconstruction in fetal MRI. Fast and accurate segmentation of the fetal brain on fetal MRI is required to achieve real-time fetal head pose estimation and motion tracking for slice re-acquisition and steering. To address this critical unmet need, in this work we analyzed the speed-accuracy performance of a variety of deep neural network models, and devised a symbolically small convolutional neural network that combines spatial details at high resolution with context features extracted at lower resolutions. We used multiple branches with skip connections to maintain high accuracy while devising a parallel combination of convolution and pooling operations as an input downsampling module to further reduce inference time. We trained our model as well as eight alternative, state-of-the-art networks with manually-labeled fetal brain MRI slices and tested on two sets of normal and challenging test cases. Experimental results show that our network achieved the highest accuracy and lowest inference time among all of the compared state-of-the-art real-time segmentation methods. We achieved average Dice scores of 97.99\% and 84.04\% on the normal and challenging test sets, respectively, with an inference time of 3.36 milliseconds per image on an NVIDIA GeForce RTX 2080 Ti. Code, data, and the trained models are available at https://github.com/bchimagine/real_time_fetal_brain_segmentation.

Fetal Brain Tissue Annotation and Segmentation Challenge Results

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Learning to segment fetal brain tissue from noisy annotations

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.

Diffusion Tensor Estimation with Transformer Neural Networks

Diffusion tensor imaging (DTI) is the most widely used tool for studying brain white matter development and degeneration. However, standard DTI estimation methods depend on a large number of high-quality measurements. This would require long scan times and can be particularly difficult to achieve with certain patient populations such as neonates. Here, we propose a method that can accurately estimate the diffusion tensor from only six diffusion-weighted measurements. Our method achieves this by learning to exploit the relationships between the diffusion signals and tensors in neighboring voxels. Our model is based on transformer networks, which represent the state of the art in modeling the relationship between signals in a sequence. In particular, our model consists of two such networks. The first network estimates the diffusion tensor based on the diffusion signals in a neighborhood of voxels. The second network provides more accurate tensor estimations by learning the relationships between the diffusion signals as well as the tensors estimated by the first network in neighboring voxels. Our experiments with three datasets show that our proposed method achieves highly accurate estimations of the diffusion tensor and is significantly superior to three competing methods. Estimations produced by our method with six measurements are comparable with those of standard estimation methods with 30-88 measurements. Hence, our method promises shorter scan times and more reliable assessment of brain white matter, particularly in non-cooperative patients such as neonates and infants.

Calibrated Diffusion Tensor Estimation

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.

Convolution-Free Medical Image Segmentation using Transformers

Like other applications in computer vision, medical image segmentation has been most successfully addressed using deep learning models that rely on the convolution operation as their main building block. Convolutions enjoy important properties such as sparse interactions, weight sharing, and translation equivariance. These properties give convolutional neural networks (CNNs) a strong and useful inductive bias for vision tasks. In this work we show that a different method, based entirely on self-attention between neighboring image patches and without any convolution operations, can achieve competitive or better results. Given a 3D image block, our network divides it into $n^3$ 3D patches, where $n=3 \text{ or } 5$ and computes a 1D embedding for each patch. The network predicts the segmentation map for the center patch of the block based on the self-attention between these patch embeddings. We show that the proposed model can achieve segmentation accuracies that are better than the state of the art CNNs on three datasets. We also propose methods for pre-training this model on large corpora of unlabeled images. Our experiments show that with pre-training the advantage of our proposed network over CNNs can be significant when labeled training data is small.

A machine learning-based method for estimating the number and orientations of major fascicles in diffusion-weighted magnetic resonance imaging

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.

Critical Assessment of Transfer Learning for Medical Image Segmentation with Fully Convolutional Neural Networks

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.