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Cardiac MRI, crucial for evaluating heart structure and function, faces limitations like slow imaging and motion artifacts. Undersampling reconstruction, especially data-driven algorithms, has emerged as a promising solution to accelerate scans and enhance imaging performance using highly under-sampled data. Nevertheless, the scarcity of publicly available cardiac k-space datasets and evaluation platform hinder the development of data-driven reconstruction algorithms. To address this issue, we organized the Cardiac MRI Reconstruction Challenge (CMRxRecon) in 2023, in collaboration with the 26th International Conference on MICCAI. CMRxRecon presented an extensive k-space dataset comprising cine and mapping raw data, accompanied by detailed annotations of cardiac anatomical structures. With overwhelming participation, the challenge attracted more than 285 teams and over 600 participants. Among them, 22 teams successfully submitted Docker containers for the testing phase, with 7 teams submitted for both cine and mapping tasks. All teams use deep learning based approaches, indicating that deep learning has predominately become a promising solution for the problem. The first-place winner of both tasks utilizes the E2E-VarNet architecture as backbones. In contrast, U-Net is still the most popular backbone for both multi-coil and single-coil reconstructions. This paper provides a comprehensive overview of the challenge design, presents a summary of the submitted results, reviews the employed methods, and offers an in-depth discussion that aims to inspire future advancements in cardiac MRI reconstruction models. The summary emphasizes the effective strategies observed in Cardiac MRI reconstruction, including backbone architecture, loss function, pre-processing techniques, physical modeling, and model complexity, thereby providing valuable insights for further developments in this field., Comment: 25 pages, 17 figures

Accelerating dynamic MRI is essential for enhancing clinical applications, such as adaptive radiotherapy, and improving patient comfort. Traditional deep learning (DL) approaches for accelerated dynamic MRI reconstruction typically rely on predefined or random subsampling patterns, applied uniformly across all temporal phases. This standard practice overlooks the potential benefits of leveraging temporal correlations and lacks the adaptability required for case-specific subsampling optimization, which holds the potential for maximizing reconstruction quality. Addressing this gap, we present a novel end-to-end framework for adaptive dynamic MRI subsampling and reconstruction. Our pipeline integrates a DL-based adaptive sampler, generating case-specific dynamic subsampling patterns, trained end-to-end with a state-of-the-art 2D dynamic reconstruction network, namely vSHARP, which effectively reconstructs the adaptive dynamic subsampled data into a moving image. Our method is assessed using dynamic cine cardiac MRI data, comparing its performance against vSHARP models that employ common subsampling trajectories, and pipelines trained to optimize dataset-specific sampling schemes alongside vSHARP reconstruction. Our results indicate superior reconstruction quality, particularly at high accelerations., Comment: 14 pages, 5 figures, 8 tables

Cone Beam CT (CBCT) is an essential imaging modality nowadays, but the image quality of CBCT still lags behind the high quality standards established by the conventional Computed Tomography. We propose LIRE+, a learned iterative scheme for fast and memory-efficient CBCT reconstruction, which is a substantially faster and more parameter-efficient alternative to the recently proposed LIRE method. LIRE+ is a rotationally-equivariant multiscale learned invertible primal-dual iterative scheme for CBCT reconstruction. Memory usage is optimized by relying on simple reversible residual networks in primal/dual cells and patch-wise computations inside the cells during forward and backward passes, while increased inference speed is achieved by making the primal-dual scheme multiscale so that the reconstruction process starts at low resolution and with low resolution primal/dual latent vectors. A LIRE+ model was trained and validated on a set of 260 + 22 thorax CT scans and tested using a set of 142 thorax CT scans with additional evaluation with and without finetuning on an out-of-distribution set of 79 Head and Neck (HN) CT scans. Our method surpasses classical and deep learning baselines, including LIRE, on the thorax test set. For a similar inference time and with only 37 % of the parameter budget, LIRE+ achieves a +0.2 dB PSNR improvement over LIRE, while being able to match the performance of LIRE in 45 % less inference time and with 28 % of the parameter budget. Rotational equivariance ensures robustness of LIRE+ to patient orientation, while LIRE and other deep learning baselines suffer from substantial performance degradation when patient orientation is unusual. On the HN dataset in the absence of finetuning, LIRE+ is generally comparable to LIRE in performance apart from a few outlier cases, whereas after identical finetuning LIRE+ demonstates a +1.02 dB PSNR improvement over LIRE.

Pulmonary nodules may be an early manifestation of lung cancer, the leading cause of cancer-related deaths among both men and women. Numerous studies have established that deep learning methods can yield high-performance levels in the detection of lung nodules in chest X-rays. However, the lack of gold-standard public datasets slows down the progression of the research and prevents benchmarking of methods for this task. To address this, we organized a public research challenge, NODE21, aimed at the detection and generation of lung nodules in chest X-rays. While the detection track assesses state-of-the-art nodule detection systems, the generation track determines the utility of nodule generation algorithms to augment training data and hence improve the performance of the detection systems. This paper summarizes the results of the NODE21 challenge and performs extensive additional experiments to examine the impact of the synthetically generated nodule training images on the detection algorithm performance., Comment: 15 pages, 5 figures

Purpose: MRI represents an important diagnostic modality; however, its inherently slow acquisition process poses challenges in obtaining fully-sampled k-space data under motion. In the absence of fully-sampled acquisitions, serving as ground truths, training deep learning algorithms in a supervised manner to predict the underlying ground truth image becomes challenging. To address this limitation, self-supervised methods have emerged as a viable alternative, leveraging available subsampled k-space data to train deep neural networks for MRI reconstruction. Nevertheless, these approaches often fall short when compared to supervised methods. Methods: We propose Joint Supervised and Self-supervised Learning (JSSL), a novel training approach for deep learning-based MRI reconstruction algorithms aimed at enhancing reconstruction quality in cases where target datasets containing fully-sampled k-space measurements are unavailable. JSSL operates by simultaneously training a model in a self-supervised learning setting, using subsampled data from the target dataset(s), and in a supervised learning manner, utilizing datasets with fully-sampled k-space data, referred to as proxy datasets. We demonstrate JSSL's efficacy using subsampled prostate or cardiac MRI data as the target datasets, with fully-sampled brain and knee, or brain, knee and prostate k-space acquisitions, respectively, as proxy datasets. Results: Our results showcase substantial improvements over conventional self-supervised methods, validated using common image quality metrics. Furthermore, we provide theoretical motivations for JSSL and establish rule-of-thumb guidelines for training MRI reconstruction models. Conclusion: JSSL effectively enhances MRI reconstruction quality in scenarios where fully-sampled k-space data is not available, leveraging the strengths of supervised learning by incorporating proxy datasets., Comment: pages, 14 figures, 6 tables

Image segmentation algorithms can be understood as a collection of pixel classifiers, for which the outcomes of nearby pixels are correlated. Classifier models can be calibrated using Inductive Conformal Prediction, but this requires holding back a sufficiently large calibration dataset for computing the distribution of non-conformity scores of the model's predictions. If one only requires only marginal calibration on the image level, this calibration set consists of all individual pixels in the images available for calibration. However, if the goal is to attain proper calibration for each individual pixel classifier, the calibration set consists of individual images. In a scenario where data are scarce (such as the medical domain), it may not always be possible to set aside sufficiently many images for this pixel-level calibration. The method we propose, dubbed ``Kandinsky calibration'', makes use of the spatial structure present in the distribution of natural images to simultaneously calibrate the classifiers of ``similar'' pixels. This can be seen as an intermediate approach between marginal (imagewise) and conditional (pixelwise) calibration, where non-conformity scores are aggregated over similar image regions, thereby making more efficient use of the images available for calibration. We run experiments on segmentation algorithms trained and calibrated on subsets of the public MS-COCO and Medical Decathlon datasets, demonstrating that Kandinsky calibration method can significantly improve the coverage. When compared to both pixelwise and imagewise calibration on little data, the Kandinsky method achieves much lower coverage errors, indicating the data efficiency of the Kandinsky calibration., Comment: 15 pages, 11 figures

Cardiac magnetic resonance imaging is a valuable non-invasive tool for identifying cardiovascular diseases. For instance, Cine MRI is the benchmark modality for assessing the cardiac function and anatomy. On the other hand, multi-contrast (T1 and T2) mapping has the potential to assess pathologies and abnormalities in the myocardium and interstitium. However, voluntary breath-holding and often arrhythmia, in combination with MRI's slow imaging speed, can lead to motion artifacts, hindering real-time acquisition image quality. Although performing accelerated acquisitions can facilitate dynamic imaging, it induces aliasing, causing low reconstructed image quality in Cine MRI and inaccurate T1 and T2 mapping estimation. In this work, inspired by related work in accelerated MRI reconstruction, we present a deep learning (DL)-based method for accelerated cine and multi-contrast reconstruction in the context of dynamic cardiac imaging. We formulate the reconstruction problem as a least squares regularized optimization task, and employ vSHARP, a state-of-the-art DL-based inverse problem solver, which incorporates half-quadratic variable splitting and the alternating direction method of multipliers with neural networks. We treat the problem in two setups; a 2D reconstruction and a 2D dynamic reconstruction task, and employ 2D and 3D deep learning networks, respectively. Our method optimizes in both the image and k-space domains, allowing for high reconstruction fidelity. Although the target data is undersampled with a Cartesian equispaced scheme, we train our model using both Cartesian and simulated non-Cartesian undersampling schemes to enhance generalization of the model to unseen data. Furthermore, our model adopts a deep neural network to learn and refine the sensitivity maps of multi-coil k-space data. Lastly, our method is jointly trained on both, undersampled cine and multi-contrast data., Comment: 12 pages, 3 figures, 2 tables. CMRxRecon Challenge, MICCAI 2023

Medical Imaging (MI) tasks, such as accelerated parallel Magnetic Resonance Imaging (MRI), often involve reconstructing an image from noisy or incomplete measurements. This amounts to solving ill-posed inverse problems, where a satisfactory closed-form analytical solution is not available. Traditional methods such as Compressed Sensing (CS) in MRI reconstruction can be time-consuming or prone to obtaining low-fidelity images. Recently, a plethora of Deep Learning (DL) approaches have demonstrated superior performance in inverse-problem solving, surpassing conventional methods. In this study, we propose vSHARP (variable Splitting Half-quadratic ADMM algorithm for Reconstruction of inverse Problems), a novel DL-based method for solving ill-posed inverse problems arising in MI. vSHARP utilizes the Half-Quadratic Variable Splitting method and employs the Alternating Direction Method of Multipliers (ADMM) to unroll the optimization process. For data consistency, vSHARP unrolls a differentiable gradient descent process in the image domain, while a DL-based denoiser, such as a U-Net architecture, is applied to enhance image quality. vSHARP also employs a dilated-convolution DL-based model to predict the Lagrange multipliers for the ADMM initialization. We evaluate vSHARP on tasks of accelerated parallel MRI Reconstruction using two distinct datasets and on accelerated parallel dynamic MRI Reconstruction using another dataset. Our comparative analysis with state-of-the-art methods demonstrates the superior performance of vSHARP in these applications., Comment: 22 pages, 9 figures, 5 tables

Lesion volume is an important predictor for prognosis in breast cancer. We make a step towards a more accurate lesion volume measurement on digital mammograms by developing a model that allows to estimate lesion volumes on processed mammograms, which are the images routinely used by radiologists in clinical practice as well as in breast cancer screening and are available in medical centers. Processed mammograms are obtained from raw mammograms, which are the X-ray data coming directly from the scanner, by applying certain vendor-specific non-linear transformations. At the core of our volume estimation method is a physics-based algorithm for measuring lesion volumes on raw mammograms. We subsequently extend this algorithm to processed mammograms via a deep learning image-to-image translation model that produces synthetic raw mammograms from processed mammograms in a multi-vendor setting. We assess the reliability and validity of our method using a dataset of 1778 mammograms with an annotated mass. Firstly, we investigate the correlations between lesion volumes computed from mediolateral oblique and craniocaudal views, with a resulting Pearson correlation of 0.93 [95% confidence interval (CI) 0.92 - 0.93]. Secondly, we compare the resulting lesion volumes from true and synthetic raw data, with a resulting Pearson correlation of 0.998 [95% CI 0.998 - 0.998] . Finally, for a subset of 100 mammograms with a malign mass and concurrent MRI examination available, we analyze the agreement between lesion volume on mammography and MRI, resulting in an intraclass correlation coefficient of 0.81 [95% CI 0.73 - 0.87] for consistency and 0.78 [95% CI 0.66 - 0.86] for absolute agreement. In conclusion, we developed an algorithm to measure mammographic lesion volume that reached excellent reliability and good validity, when using MRI as ground truth.

Magnetic resonance imaging (MRI) is the most sensitive technique for breast cancer detection among current clinical imaging modalities. Contrast-enhanced MRI (CE-MRI) provides superior differentiation between tumors and invaded healthy tissue, and has become an indispensable technique in the detection and evaluation of cancer. However, the use of gadolinium-based contrast agents (GBCA) to obtain CE-MRI may be associated with nephrogenic systemic fibrosis and may lead to bioaccumulation in the brain, posing a potential risk to human health. Moreover, and likely more important, the use of gadolinium-based contrast agents requires the cannulation of a vein, and the injection of the contrast media which is cumbersome and places a burden on the patient. To reduce the use of contrast agents, diffusion-weighted imaging (DWI) is emerging as a key imaging technique, although currently usually complementing breast CE-MRI. In this study, we develop a multi-sequence fusion network to synthesize CE-MRI based on T1-weighted MRI and DWIs. DWIs with different b-values are fused to efficiently utilize the difference features of DWIs. Rather than proposing a pure data-driven approach, we invent a multi-sequence attention module to obtain refined feature maps, and leverage hierarchical representation information fused at different scales while utilizing the contributions from different sequences from a model-driven approach by introducing the weighted difference module. The results show that the multi-b-value DWI-based fusion model can potentially be used to synthesize CE-MRI, thus theoretically reducing or avoiding the use of GBCA, thereby minimizing the burden to patients. Our code is available at \url{https://github.com/Netherlands-Cancer-Institute/CE-MRI}., Comment: This paper has been accepted by MICCAI 2023

Deep Neural Networks (DNNs) are widely used for their ability to effectively approximate large classes of functions. This flexibility, however, makes the strict enforcement of constraints on DNNs an open problem. Here we present a framework that, under mild assumptions, allows the exact enforcement of constraints on parameterized sets of functions such as DNNs. Instead of imposing "soft'' constraints via additional terms in the loss, we restrict (a subset of) the DNN parameters to a submanifold on which the constraints are satisfied exactly throughout the entire training procedure. We focus on constraints that are outside the scope of equivariant networks used in Geometric Deep Learning. As a major example of the framework, we restrict filters of a Convolutional Neural Network (CNN) to be wavelets, and apply these wavelet networks to the task of contour prediction in the medical domain., Comment: 50 pages, 12 figures, 2 tables

Magnetic resonance imaging (MRI) is highly sensitive for lesion detection in the breasts. Sequences obtained with different settings can capture the specific characteristics of lesions. Such multi-parameter MRI information has been shown to improve radiologist performance in lesion classification, as well as improving the performance of artificial intelligence models in various tasks. However, obtaining multi-parameter MRI makes the examination costly in both financial and time perspectives, and there may be safety concerns for special populations, thus making acquisition of the full spectrum of MRI sequences less durable. In this study, different than naive input fusion or feature concatenation from existing MRI parameters, a novel $\textbf{I}$ntegrated MRI $\textbf{M}$ulti-$\textbf{P}$arameter reinf$\textbf{O}$rcement fusion generato$\textbf{R}$ wi$\textbf{T}$h $\textbf{A}$tte$\textbf{NT}$ion Network (IMPORTANT-Net) is developed to generate missing parameters. First, the parameter reconstruction module is used to encode and restore the existing MRI parameters to obtain the corresponding latent representation information at any scale level. Then the multi-parameter fusion with attention module enables the interaction of the encoded information from different parameters through a set of algorithmic strategies, and applies different weights to the information through the attention mechanism after information fusion to obtain refined representation information. Finally, a reinforcement fusion scheme embedded in a $V^{-}$-shape generation module is used to combine the hierarchical representations to generate the missing MRI parameter. Results showed that our IMPORTANT-Net is capable of generating missing MRI parameters and outperforms comparable state-of-the-art networks. Our code is available at https://github.com/Netherlands-Cancer-Institute/MRI_IMPORTANT_NET.

Multi-sequence MRIs can be necessary for reliable diagnosis in clinical practice due to the complimentary information within sequences. However, redundant information exists across sequences, which interferes with mining efficient representations by modern machine learning or deep learning models. To handle various clinical scenarios, we propose a sequence-to-sequence generation framework (Seq2Seq) for imaging-differentiation representation learning. In this study, not only do we propose arbitrary 3D/4D sequence generation within one model to generate any specified target sequence, but also we are able to rank the importance of each sequence based on a new metric estimating the difficulty of a sequence being generated. Furthermore, we also exploit the generation inability of the model to extract regions that contain unique information for each sequence. We conduct extensive experiments using three datasets including a toy dataset of 20,000 simulated subjects, a brain MRI dataset of 1,251 subjects, and a breast MRI dataset of 2,101 subjects, to demonstrate that (1) our proposed Seq2Seq is efficient and lightweight for complex clinical datasets and can achieve excellent image quality; (2) top-ranking sequences can be used to replace complete sequences with non-inferior performance; (3) combining MRI with our imaging-differentiation map leads to better performance in clinical tasks such as glioblastoma MGMT promoter methylation status prediction and breast cancer pathological complete response status prediction. Our code is available at https://github.com/fiy2W/mri_seq2seq.

Acquiring fully-sampled MRI $k$-space data is time-consuming, and collecting accelerated data can reduce the acquisition time. Employing 2D Cartesian-rectilinear subsampling schemes is a conventional approach for accelerated acquisitions; however, this often results in imprecise reconstructions, even with the use of Deep Learning (DL), especially at high acceleration factors. Non-rectilinear or non-Cartesian trajectories can be implemented in MRI scanners as alternative subsampling options. This work investigates the impact of the $k$-space subsampling scheme on the quality of reconstructed accelerated MRI measurements produced by trained DL models. The Recurrent Variational Network (RecurrentVarNet) was used as the DL-based MRI-reconstruction architecture. Cartesian, fully-sampled multi-coil $k$-space measurements from three datasets were retrospectively subsampled with different accelerations using eight distinct subsampling schemes: four Cartesian-rectilinear, two Cartesian non-rectilinear, and two non-Cartesian. Experiments were conducted in two frameworks: scheme-specific, where a distinct model was trained and evaluated for each dataset-subsampling scheme pair, and multi-scheme, where for each dataset a single model was trained on data randomly subsampled by any of the eight schemes and evaluated on data subsampled by all schemes. In both frameworks, RecurrentVarNets trained and evaluated on non-rectilinearly subsampled data demonstrated superior performance, particularly for high accelerations. In the multi-scheme setting, reconstruction performance on rectilinearly subsampled data improved when compared to the scheme-specific experiments. Our findings demonstrate the potential for using DL-based methods, trained on non-rectilinearly subsampled measurements, to optimize scan time and image quality., Comment: 22 pages, 12 figures, 5 tables

To correct for respiratory motion in PET imaging, an interpretable and unsupervised deep learning technique, FlowNet-PET, was constructed. The network was trained to predict the optical flow between two PET frames from different breathing amplitude ranges. The trained model aligns different retrospectively-gated PET images, providing a final image with similar counting statistics as a non-gated image, but without the blurring effects. FlowNet-PET was applied to anthropomorphic digital phantom data, which provided the possibility to design robust metrics to quantify the corrections. When comparing the predicted optical flows to the ground truths, the median absolute error was found to be smaller than the pixel and slice widths. The improvements were illustrated by comparing against images without motion and computing the intersection over union (IoU) of the tumors as well as the enclosed activity and coefficient of variation (CoV) within the no-motion tumor volume before and after the corrections were applied. The average relative improvements provided by the network were 64%, 89%, and 75% for the IoU, total activity, and CoV, respectively. FlowNet-PET achieved similar results as the conventional retrospective phase binning approach, but only required one sixth of the scan duration. The code and data have been made publicly available (https://github.com/teaghan/FlowNet_PET).

Cone Beam CT plays an important role in many medical fields nowadays, but the potential of this imaging modality is hampered by lower image quality compared to the conventional CT. A lot of recent research has been directed towards reconstruction methods relying on deep learning. However, practical application of deep learning to CBCT reconstruction is complicated by several issues, such as exceedingly high memory costs of deep learning methods for fully 3D data. In this work, we address these limitations and propose LIRE: a learned invertible primal-dual iterative scheme for Cone Beam CT reconstruction. Memory requirements of the network are substantially reduced while preserving its expressive power, enabling us to train on data with isotropic 2mm voxel spacing, clinically-relevant projection count and detector panel resolution on current hardware with 24 GB VRAM. Two LIRE models for small and for large Field-of-View setting were trained and validated on a set of 260 + 22 thorax CT scans and tested using a set of 142 thorax CT scans plus an out-of-distribution dataset of 79 head \& neck CT scans. For both settings, our method surpasses the classical methods and the deep learning baselines on both test sets. On the thorax CT set, our method achieves PSNR of 33.84 $\pm$ 2.28 for the small FoV setting and 35.14 $\pm$ 2.69 for the large FoV setting; U-Net baseline achieves PSNR of 33.08 $\pm$ 1.75 and 34.29 $\pm$ 2.71 respectively. On the head \& neck CT set, our method achieves PSNR of 39.35 $\pm$ 1.75 for the small FoV setting and 41.21 $\pm$ 1.41 for the large FoV setting; U-Net baseline achieves PSNR of 33.08 $\pm$ 1.75 and 34.29 $\pm$ 2.71 respectively. Additionally, we demonstrate that LIRE can be finetuned to reconstruct high-resolution CBCT data with the same geometry but 1mm voxel spacing and higher detector panel resolution, where it outperforms the U-Net baseline as well.

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing., Comment: federated learning, deep learning, convolutional neural network, segmentation, brain tumor, glioma, glioblastoma, FeTS, BraTS

Magnetic Resonance Imaging can produce detailed images of the anatomy and physiology of the human body that can assist doctors in diagnosing and treating pathologies such as tumours. However, MRI suffers from very long acquisition times that make it susceptible to patient motion artifacts and limit its potential to deliver dynamic treatments. Conventional approaches such as Parallel Imaging and Compressed Sensing allow for an increase in MRI acquisition speed by reconstructing MR images from sub-sampled MRI data acquired using multiple receiver coils. Recent advancements in Deep Learning combined with Parallel Imaging and Compressed Sensing techniques have the potential to produce high-fidelity reconstructions from highly accelerated MRI data. In this work we present a novel Deep Learning-based Inverse Problem solver applied to the task of Accelerated MRI Reconstruction, called the Recurrent Variational Network (RecurrentVarNet), by exploiting the properties of Convolutional Recurrent Neural Networks and unrolled algorithms for solving Inverse Problems. The RecurrentVarNet consists of multiple recurrent blocks, each responsible for one iteration of the unrolled variational optimization scheme for solving the inverse problem of multi-coil Accelerated MRI Reconstruction. Contrary to traditional approaches, the optimization steps are performed in the observation domain ($k$-space) instead of the image domain. Each block of the RecurrentVarNet refines the observed $k$-space and comprises a data consistency term and a recurrent unit which takes as input a learned hidden state and the prediction of the previous block. Our proposed method achieves new state of the art qualitative and quantitative reconstruction results on 5-fold and 10-fold accelerated data from a public multi-coil brain dataset, outperforming previous conventional and deep learning-based approaches., Comment: 18 pages, 10 figures, 3 tables, CVPR 22

We propose a novel deep learning framework for fast prediction of boundaries of two-dimensional simply connected domains using wavelets and Multi Resolution Analysis (MRA). The boundaries are modelled as (piecewise) smooth closed curves using wavelets and the so-called Pyramid Algorithm. Our network architecture is a hybrid analog of the U-Net, where the down-sampling path is a two-dimensional encoder with learnable filters, and the upsampling path is a one-dimensional decoder, which builds curves up from low to high resolution levels. Any wavelet basis induced by a MRA can be used. This flexibility allows for incorporation of priors on the smoothness of curves. The effectiveness of the proposed method is demonstrated by delineating boundaries of simply connected domains (organs) in medical images using Debauches wavelets and comparing performance with a U-Net baseline. Our model demonstrates up to 5x faster inference speed compared to the U-Net, while maintaining similar performance in terms of Dice score and Hausdorff distance., Comment: 19 pages, 10 figures, 1 table

We present WeakSTIL, an interpretable two-stage weak label deep learning pipeline for scoring the percentage of stromal tumor infiltrating lymphocytes (sTIL%) in H&E-stained whole-slide images (WSIs) of breast cancer tissue. The sTIL% score is a prognostic and predictive biomarker for many solid tumor types. However, due to the high labeling efforts and high intra- and interobserver variability within and between expert annotators, this biomarker is currently not used in routine clinical decision making. WeakSTIL compresses tiles of a WSI using a feature extractor pre-trained with self-supervised learning on unlabeled histopathology data and learns to predict precise sTIL% scores for each tile in the tumor bed by using a multiple instance learning regressor that only requires a weak WSI-level label. By requiring only a weak label, we overcome the large annotation efforts required to train currently existing TIL detection methods. We show that WeakSTIL is at least as good as other TIL detection methods when predicting the WSI-level sTIL% score, reaching a coefficient of determination of $0.45\pm0.15$ when compared to scores generated by an expert pathologist, and an AUC of $0.89\pm0.05$ when treating it as the clinically interesting sTIL-high vs sTIL-low classification task. Additionally, we show that the intermediate tile-level predictions of WeakSTIL are highly interpretable, which suggests that WeakSTIL pays attention to latent features related to the number of TILs and the tissue type. In the future, WeakSTIL may be used to provide consistent and interpretable sTIL% predictions to stratify breast cancer patients into targeted therapy arms., Comment: 8 pages, 8 figures, 1 table, 4 pages supplementary

In spite of its extensive adaptation in almost every medical diagnostic and examinatorial application, Magnetic Resonance Imaging (MRI) is still a slow imaging modality which limits its use for dynamic imaging. In recent years, Parallel Imaging (PI) and Compressed Sensing (CS) have been utilised to accelerate the MRI acquisition. In clinical settings, subsampling the k-space measurements during scanning time using Cartesian trajectories, such as rectilinear sampling, is currently the most conventional CS approach applied which, however, is prone to producing aliased reconstructions. With the advent of the involvement of Deep Learning (DL) in accelerating the MRI, reconstructing faithful images from subsampled data became increasingly promising. Retrospectively applying a subsampling mask onto the k-space data is a way of simulating the accelerated acquisition of k-space data in real clinical setting. In this paper we compare and provide a review for the effect of applying either rectilinear or radial retrospective subsampling on the quality of the reconstructions outputted by trained deep neural networks. With the same choice of hyper-parameters, we train and evaluate two distinct Recurrent Inference Machines (RIMs), one for each type of subsampling. The qualitative and quantitative results of our experiments indicate that the model trained on data with radial subsampling attains higher performance and learns to estimate reconstructions with higher fidelity paving the way for other DL approaches to involve radial subsampling., Comment: 9 pages, 7 figures, 1 table

We propose a Deep learning-based weak label learning method for analyzing whole slide images (WSIs) of Hematoxylin and Eosin (H&E) stained tumor tissue not requiring pixel-level or tile-level annotations using Self-supervised pre-training and heterogeneity-aware deep Multiple Instance LEarning (DeepSMILE). We apply DeepSMILE to the task of Homologous recombination deficiency (HRD) and microsatellite instability (MSI) prediction. We utilize contrastive self-supervised learning to pre-train a feature extractor on histopathology tiles of cancer tissue. Additionally, we use variability-aware deep multiple instance learning to learn the tile feature aggregation function while modeling tumor heterogeneity. For MSI prediction in a tumor-annotated and color normalized subset of TCGA-CRC (n=360 patients), contrastive self-supervised learning improves the tile supervision baseline from 0.77 to 0.87 AUROC, on par with our proposed DeepSMILE method. On TCGA-BC (n=1041 patients) without any manual annotations, DeepSMILE improves HRD classification performance from 0.77 to 0.81 AUROC compared to tile supervision with either a self-supervised or ImageNet pre-trained feature extractor. Our proposed methods reach the baseline performance using only 40% of the labeled data on both datasets. These improvements suggest we can use standard self-supervised learning techniques combined with multiple instance learning in the histopathology domain to improve genomic label classification performance with fewer labeled data., Comment: Main paper: 14 pages, 2 tables, 1 algorithm, 3 figures. Supplementary material: 3 pages

Object localisation, in the context of regular images, often depicts objects like people or cars. In these images, there is typically a relatively small number of objects per class, which usually is manageable to annotate. However, outside the setting of regular images, we are often confronted with a different situation. In computational pathology, digitised tissue sections are extremely large images, whose dimensions quickly exceed 250'000x250'000 pixels, where relevant objects, such as tumour cells or lymphocytes can quickly number in the millions. Annotating them all is practically impossible and annotating sparsely a few, out of many more, is the only possibility. Unfortunately, learning from sparse annotations, or sparse-shot learning, clashes with standard supervised learning because what is not annotated is treated as a negative. However, assigning negative labels to what are true positives leads to confusion in the gradients and biased learning. To this end, we present exclusive cross-entropy, which slows down the biased learning by examining the second-order loss derivatives in order to drop the loss terms corresponding to likely biased terms. Experiments on nine datasets and two different localisation tasks, detection with YOLLO and segmentation with Unet, show that we obtain considerable improvements compared to cross-entropy or focal loss, while often reaching the best possible performance for the model with only 10-40% of annotations., Comment: 11 pages, 5 figures, 3 tables

Purpose: We propose a deep learning-based computer-aided detection (CADe) method to detect breast lesions in ultrafast DCE-MRI sequences. This method uses both the three-dimensional spatial information and temporal information obtained from the early-phase of the dynamic acquisition. Methods: The proposed CADe method, based on a modified 3D RetinaNet model, operates on ultrafast T1 weighted sequences, which are preprocessed for motion compensation, temporal normalization, and are cropped before passing into the model. The model is optimized to enable the detection of relatively small breast lesions in a screening setting, focusing on detection of lesions that are harder to differentiate from confounding structures inside the breast. Results: The method was developed based on a dataset consisting of 489 ultrafast MRI studies obtained from 462 patients containing a total of 572 lesions (365 malignant, 207 benign) and achieved a detection rate, sensitivity, and detection rate of benign lesions of 0.90 (0.876-0.934), 0.95 (0.934-0.980), and 0.81 (0.751-0.871) at 4 false positives per normal breast with 10-fold cross-testing, respectively. Conclusions: The deep learning architecture used for the proposed CADe application can efficiently detect benign and malignant lesions on ultrafast DCE-MRI. Furthermore, utilizing the less visible hard-to detect-lesions in training improves the learning process and, subsequently, detection of malignant breast lesions.

Accelerating MRI scans is one of the principal outstanding problems in the MRI research community. Towards this goal, we hosted the second fastMRI competition targeted towards reconstructing MR images with subsampled k-space data. We provided participants with data from 7,299 clinical brain scans (de-identified via a HIPAA-compliant procedure by NYU Langone Health), holding back the fully-sampled data from 894 of these scans for challenge evaluation purposes. In contrast to the 2019 challenge, we focused our radiologist evaluations on pathological assessment in brain images. We also debuted a new Transfer track that required participants to submit models evaluated on MRI scanners from outside the training set. We received 19 submissions from eight different groups. Results showed one team scoring best in both SSIM scores and qualitative radiologist evaluations. We also performed analysis on alternative metrics to mitigate the effects of background noise and collected feedback from the participants to inform future challenges. Lastly, we identify common failure modes across the submissions, highlighting areas of need for future research in the MRI reconstruction community., Comment: M. J. Muckley and B. Riemenschneider contributed equally to this work. This updates to version accepted in IEEE Transactions on Medical Imaging. It includes a rewrite of Section II.E as well as minor changes and corrections

Deep-learning-based brain magnetic resonance imaging (MRI) reconstruction methods have the potential to accelerate the MRI acquisition process. Nevertheless, the scientific community lacks appropriate benchmarks to assess MRI reconstruction quality of high-resolution brain images, and evaluate how these proposed algorithms will behave in the presence of small, but expected data distribution shifts. The Multi-Coil Magnetic Resonance Image (MC-MRI) Reconstruction Challenge provides a benchmark that aims at addressing these issues, using a large dataset of high-resolution, three-dimensional, T1-weighted MRI scans. The challenge has two primary goals: 1) to compare different MRI reconstruction models on this dataset and 2) to assess the generalizability of these models to data acquired with a different number of receiver coils. In this paper, we describe the challenge experimental design, and summarize the results of a set of baseline and state of the art brain MRI reconstruction models. We provide relevant comparative information on the current MRI reconstruction state-of-the-art and highlight the challenges of obtaining generalizable models that are required prior to broader clinical adoption. The MC-MRI benchmark data, evaluation code and current challenge leaderboard are publicly available. They provide an objective performance assessment for future developments in the field of brain MRI reconstruction.

Reconstruction of digital breast tomosynthesis is a challenging problem due to the limited angle data available in such systems. Due to memory limitations, deep learning-based methods can help improve these reconstructions, but can not (yet) attain sufficiently high resolution. In addition to this practical issue, questions remain on the possibility of such models introducing 'ghost' information from the training data that is not compatible with the projection data. To take advantage of some of the benefits of deep learning-based reconstructions while avoiding these limitations, we propose to use the low resolution deep learning-based reconstruction as an initialization of a regular high resolution iterative method. The network was trained using digital phantoms, some based on a mathematical model and some derived from patient dedicated breast CT scans. The output of this network was then used as initialization for 10 000 iterations of MLTR for nine patient based phantoms that were not included in the training. The same nine cases were also reconstructed without any initialization for comparison. The reconstructions including initialization were found to reach a lower mean squared error than those without, and visual inspection found much improved retrieval of the breast outline and depiction of the skin, confirming that adding the deep learning-based initialization adds valuable information to the reconstruction., Comment: Presented at the 6th International Conference on Image Formation in X-Ray Computed Tomography (CT-meeting), August 6, 2020, Regensburg, Germany

The two-dimensional nature of mammography makes estimation of the overall breast density challenging, and estimation of the true patient-specific radiation dose impossible. Digital breast tomosynthesis (DBT), a pseudo-3D technique, is now commonly used in breast cancer screening and diagnostics. Still, the severely limited 3rd dimension information in DBT has not been used, until now, to estimate the true breast density or the patient-specific dose. This study proposes a reconstruction algorithm for DBT based on deep learning specifically optimized for these tasks. The algorithm, which we name DBToR, is based on unrolling a proximal-dual optimization method. The proximal operators are replaced with convolutional neural networks and prior knowledge is included in the model. This extends previous work on a deep learning-based reconstruction model by providing both the primal and the dual blocks with breast thickness information, which is available in DBT. Training and testing of the model were performed using virtual patient phantoms from two different sources. Reconstruction performance, and accuracy in estimation of breast density and radiation dose, were estimated, showing high accuracy (density <+/-3%; dose <+/-20%) without bias, significantly improving on the current state-of-the-art. This work also lays the groundwork for developing a deep learning-based reconstruction algorithm for the task of image interpretation by radiologists., Comment: Accepted in Medical Image Analysis

Unpaired image-to-image translation has attracted significant interest due to the invention of CycleGAN, a method which utilizes a combination of adversarial and cycle consistency losses to avoid the need for paired data. It is known that the CycleGAN problem might admit multiple solutions, and our goal in this paper is to analyze the space of exact solutions and to give perturbation bounds for approximate solutions. We show theoretically that the exact solution space is invariant with respect to automorphisms of the underlying probability spaces, and, furthermore, that the group of automorphisms acts freely and transitively on the space of exact solutions. We examine the case of zero `pure' CycleGAN loss first in its generality, and, subsequently, expand our analysis to approximate solutions for `extended' CycleGAN loss where identity loss term is included. In order to demonstrate that these results are applicable, we show that under mild conditions nontrivial smooth automorphisms exist. Furthermore, we provide empirical evidence that neural networks can learn these automorphisms with unexpected and unwanted results. We conclude that finding optimal solutions to the CycleGAN loss does not necessarily lead to the envisioned result in image-to-image translation tasks and that underlying hidden symmetries can render the result utterly useless., Comment: Accepted at ICLR 2020

We, team AImsterdam, summarize our submission to the fastMRI challenge (Zbontar et al., 2018). Our approach builds on recent advances in invertible learning to infer models as presented in Putzky and Welling (2019). Both, our single-coil and our multi-coil model share the same basic architecture., Comment: Abstract submitted to the fastMRI challenge

We introduce the learned simultaneous iterative reconstruction technique (SIRT) for tomographic reconstruction. The learned SIRT algorithm is a deep learning based reconstruction method combining model knowledge with a learned component. The algorithm is trained by mapping raw measured data to the reconstruction results over several iterations. The Learned SIRT algorithm is applied to a cone beam geometry on a circular orbit, a challenging problem for learned methods due to its 3D geometry and its inherent inability to completely capture the patient anatomy. A comparison of 2D reconstructions is shown, where the learned SIRT approach produces reconstructions with superior peak signal to noise ratio (PSNR) and structural similarity (SSIM), compared to FBP, SIRT and U-net post-processing and similar PSNR and SSIM compared to the learned primal dual algorithm. Similar results are shown for cone beam geometry reconstructions of a 3D Shepp Logan phantom, where we obtain between 9.9 and 28.1 dB improvement over FBP with a substantial improvement in SSIM. Finally we show that our algorithm scales to clinically relevant problems, and performs well when applied to measurements of a physical phantom.

Convolutional Neural Networks (CNN) have had a huge success in many areas of computer vision and medical image analysis. However, there is still an immense potential for performance improvement in mammogram breast cancer detection Computer-Aided Detection (CAD) systems by integrating all the information that the radiologist utilizes, such as symmetry and temporal data. In this work, we proposed a patch based multi-input CNN that learns symmetrical difference to detect breast masses. The network was trained on a large-scale dataset of 28294 mammogram images. The performance was compared to a baseline architecture without symmetry context using Area Under the ROC Curve (AUC) and Competition Performance Metric (CPM). At candidate level, AUC value of 0.933 with 95% confidence interval of [0.920, 0.954] was obtained when symmetry information is incorporated in comparison with baseline architecture which yielded AUC value of 0.929 with [0.919, 0.947] confidence interval. By incorporating symmetrical information, although there was no a significant candidate level performance again (p = 0.111), we have found a compelling result at exam level with CPM value of 0.733 (p = 0.001). We believe that including temporal data, and adding benign class to the dataset could improve the detection performance., Comment: 8 pages, 7 figures, accepted in MICCAI 2018 Breast Image Analysis (BIA)

Computer-aided detection aims to improve breast cancer screening programs by helping radiologists to evaluate digital mammography (DM) exams. DM exams are generated by devices from different vendors, with diverse characteristics between and even within vendors. Physical properties of these devices and postprocessing of the images can greatly influence the resulting mammogram. This results in the fact that a deep learning model trained on data from one vendor cannot readily be applied to data from another vendor. This paper investigates the use of tailored transfer learning methods based on adversarial learning to tackle this problem. We consider a database of DM exams (mostly bilateral and two views) generated by Hologic and Siemens vendors. We analyze two transfer learning settings: 1) unsupervised transfer, where Hologic data with soft lesion annotation at pixel level and Siemens unlabelled data are used to annotate images in the latter data; 2) weak supervised transfer, where exam level labels for images from the Siemens mammograph are available. We propose tailored variants of recent state-of-the-art methods for transfer learning which take into account the class imbalance and incorporate knowledge provided by the annotations at exam level. Results of experiments indicate the beneficial effect of transfer learning in both transfer settings. Notably, at 0.02 false positives per image, we achieve a sensitivity of 0.37, compared to 0.30 of a baseline with no transfer. Results indicate that using exam level annotations gives an additional increase in sensitivity., Comment: Submitted to SPIE MI 2019

Digital breast tomosynthesis is rapidly replacing digital mammography as the basic x-ray technique for evaluation of the breasts. However, the sparse sampling and limited angular range gives rise to different artifacts, which manufacturers try to solve in several ways. In this study we propose an extension of the Learned Primal-Dual algorithm for digital breast tomosynthesis. The Learned Primal-Dual algorithm is a deep neural network consisting of several `reconstruction blocks', which take in raw sinogram data as the initial input, perform a forward and a backward pass by taking projections and back-projections, and use a convolutional neural network to produce an intermediate reconstruction result which is then improved further by the successive reconstruction block. We extend the architecture by providing breast thickness measurements as a mask to the neural network and allow it to learn how to use this thickness mask. We have trained the algorithm on digital phantoms and the corresponding noise-free/noisy projections, and then tested the algorithm on digital phantoms for varying level of noise. Reconstruction performance of the algorithms was compared visually, using MSE loss and Structural Similarity Index. Results indicate that the proposed algorithm outperforms the baseline iterative reconstruction algorithm in terms of reconstruction quality for both breast edges and internal structures and is robust to noise., Comment: 4 pages, 2 figures, submitted to SPIE

Computer-aided detection or decision support systems aim to improve breast cancer screening programs by helping radiologists to evaluate digital mammography (DM) exams. Commonly such methods proceed in two steps: selection of candidate regions for malignancy, and later classification as either malignant or not. In this study, we present a candidate detection method based on deep learning to automatically detect and additionally segment soft tissue lesions in DM. A database of DM exams (mostly bilateral and two views) was collected from our institutional archive. In total, 7196 DM exams (28294 DM images) acquired with systems from three different vendors (General Electric, Siemens, Hologic) were collected, of which 2883 contained malignant lesions verified with histopathology. Data was randomly split on an exam level into training (50\%), validation (10\%) and testing (40\%) of deep neural network with u-net architecture. The u-net classifies the image but also provides lesion segmentation. Free receiver operating characteristic (FROC) analysis was used to evaluate the model, on an image and on an exam level. On an image level, a maximum sensitivity of 0.94 at 7.93 false positives (FP) per image was achieved. Similarly, per exam a maximum sensitivity of 0.98 at 7.81 FP per image was achieved. In conclusion, the method could be used as a candidate selection model with high accuracy and with the additional information of lesion segmentation., Comment: To appear in IWBI 2018