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Adversarial learning helps generative models translate MRI from source to target sequence when lacking paired samples. However, implementing MRI synthesis with adversarial learning in clinical settings is challenging due to training instability and mode collapse. To address this issue, we leverage intermediate sequences to estimate the common latent space among multi-sequence MRI, enabling the reconstruction of distinct sequences from the common latent space. We propose a generative model that compresses discrete representations of each sequence to estimate the Gaussian distribution of vector-quantized common (VQC) latent space between multiple sequences. Moreover, we improve the latent space consistency with contrastive learning and increase model stability by domain augmentation. Experiments using BraTS2021 dataset show that our non-adversarial model outperforms other GAN-based methods, and VQC latent space aids our model to achieve (1) anti-interference ability, which can eliminate the effects of noise, bias fields, and artifacts, and (2) solid semantic representation ability, with the potential of one-shot segmentation. Our code is publicly available.

Current research in breast cancer Magnetic Resonance Imaging (MRI), especially with Artificial Intelligence (AI), faces challenges due to the lack of expert segmentations. To address this, we introduce the MAMA-MIA dataset, comprising 1506 multi-center dynamic contrast-enhanced MRI cases with expert segmentations of primary tumors and non-mass enhancement areas. These cases were sourced from four publicly available collections in The Cancer Imaging Archive (TCIA). Initially, we trained a deep learning model to automatically segment the cases, generating preliminary segmentations that significantly reduced expert segmentation time. Sixteen experts, averaging 9 years of experience in breast cancer, then corrected these segmentations, resulting in the final expert segmentations. Additionally, two radiologists conducted a visual inspection of the automatic segmentations to support future quality control studies. Alongside the expert segmentations, we provide 49 harmonized demographic and clinical variables and the pretrained weights of the well-known nnUNet architecture trained using the DCE-MRI full-images and expert segmentations. This dataset aims to accelerate the development and benchmarking of deep learning models and foster innovation in breast cancer diagnostics and treatment planning., Comment: 15 paes, 7 figures, 3 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.

Asymmetry is a crucial characteristic of bilateral mammograms (Bi-MG) when abnormalities are developing. It is widely utilized by radiologists for diagnosis. The question of 'what the symmetrical Bi-MG would look like when the asymmetrical abnormalities have been removed ?' has not yet received strong attention in the development of algorithms on mammograms. Addressing this question could provide valuable insights into mammographic anatomy and aid in diagnostic interpretation. Hence, we propose a novel framework, DisAsymNet, which utilizes asymmetrical abnormality transformer guided self-adversarial learning for disentangling abnormalities and symmetric Bi-MG. At the same time, our proposed method is partially guided by randomly synthesized abnormalities. We conduct experiments on three public and one in-house dataset, and demonstrate that our method outperforms existing methods in abnormality classification, segmentation, and localization tasks. Additionally, reconstructed normal mammograms can provide insights toward better interpretable visual cues for clinical diagnosis. The code will be accessible to the public.

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

Multi-sequence MRI is valuable in clinical settings for reliable diagnosis and treatment prognosis, but some sequences may be unusable or missing for various reasons. To address this issue, MRI synthesis is a potential solution. Recent deep learning-based methods have achieved good performance in combining multiple available sequences for missing sequence synthesis. Despite their success, these methods lack the ability to quantify the contributions of different input sequences and estimate the quality of generated images, making it hard to be practical. Hence, we propose an explainable task-specific synthesis network, which adapts weights automatically for specific sequence generation tasks and provides interpretability and reliability from two sides: (1) visualize the contribution of each input sequence in the fusion stage by a trainable task-specific weighted average module; (2) highlight the area the network tried to refine during synthesizing by a task-specific attention module. We conduct experiments on the BraTS2021 dataset of 1251 subjects, and results on arbitrary sequence synthesis indicate that the proposed method achieves better performance than the state-of-the-art methods. Our code is available at \url{https://github.com/fiy2W/mri_seq2seq}.

Deep learning-based deformable registration methods have been widely investigated in diverse medical applications. Learning-based deformable registration relies on weighted objective functions trading off registration accuracy and smoothness of the deformation field. Therefore, they inevitably require tuning the hyperparameter for optimal registration performance. Tuning the hyperparameters is highly computationally expensive and introduces undesired dependencies on domain knowledge. In this study, we construct a registration model based on the gradient surgery mechanism, named GSMorph, to achieve a hyperparameter-free balance on multiple losses. In GSMorph, we reformulate the optimization procedure by projecting the gradient of similarity loss orthogonally to the plane associated with the smoothness constraint, rather than additionally introducing a hyperparameter to balance these two competing terms. Furthermore, our method is model-agnostic and can be merged into any deep registration network without introducing extra parameters or slowing down inference. In this study, We compared our method with state-of-the-art (SOTA) deformable registration approaches over two publicly available cardiac MRI datasets. GSMorph proves superior to five SOTA learning-based registration models and two conventional registration techniques, SyN and Demons, on both registration accuracy and smoothness., Comment: Accepted at MICCAI 2023

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.

Domain adaptation has been widely adopted to transfer styles across multi-vendors and multi-centers, as well as to complement the missing modalities. In this challenge, we proposed an unsupervised domain adaptation framework for cross-modality vestibular schwannoma (VS) and cochlea segmentation and Koos grade prediction. We learn the shared representation from both ceT1 and hrT2 images and recover another modality from the latent representation, and we also utilize proxy tasks of VS segmentation and brain parcellation to restrict the consistency of image structures in domain adaptation. After generating missing modalities, the nnU-Net model is utilized for VS and cochlea segmentation, while a semi-supervised contrastive learning pre-train approach is employed to improve the model performance for Koos grade prediction. On CrossMoDA validation phase Leaderboard, our method received rank 4 in task1 with a mean Dice score of 0.8394 and rank 2 in task2 with Macro-Average Mean Square Error of 0.3941. Our code is available at https://github.com/fiy2W/cmda2022.superpolymerization.

Tumor infiltration of the recurrent laryngeal nerve (RLN) is a contraindication for robotic thyroidectomy and can be difficult to detect via standard laryngoscopy. Ultrasound (US) is a viable alternative for RLN detection due to its safety and ability to provide real-time feedback. However, the tininess of the RLN, with a diameter typically less than 3mm, poses significant challenges to the accurate localization of the RLN. In this work, we propose a knowledge-driven framework for RLN localization, mimicking the standard approach surgeons take to identify the RLN according to its surrounding organs. We construct a prior anatomical model based on the inherent relative spatial relationships between organs. Through Bayesian shape alignment (BSA), we obtain the candidate coordinates of the center of a region of interest (ROI) that encloses the RLN. The ROI allows a decreased field of view for determining the refined centroid of the RLN using a dual-path identification network, based on multi-scale semantic information. Experimental results indicate that the proposed method achieves superior hit rates and substantially smaller distance errors compared with state-of-the-art methods., Comment: Early Accepted by MICCAI 2022

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.

In medical-data driven learning, 3D convolutional neural networks (CNNs) have started to show superior performance to 2D CNNs in numerous deep learning tasks, proving the added value of 3D spatial information in feature representation. However, the difficulty in collecting more training samples to converge, more computational resources and longer execution time make this approach less applied. Also, applying transfer learning on 3D CNN is challenging due to a lack of publicly available pre-trained 3D models. To tackle these issues, we proposed a novel 2D strategical representation of volumetric data, namely 2.75D. In this work, the spatial information of 3D images is captured in a single 2D view by a spiral-spinning technique. As a result, 2D CNN networks can also be used to learn volumetric information. Besides, we can fully leverage pre-trained 2D CNNs for downstream vision problems. We also explore a multi-view 2.75D strategy, 2.75D 3 channels (2.75Dx3), to boost the advantage of 2.75D. We evaluated the proposed methods on three public datasets with different modalities or organs (Lung CT, Breast MRI, and Prostate MRI), against their 2D, 2.5D, and 3D counterparts in classification tasks. Results show that the proposed methods significantly outperform other counterparts when all methods were trained from scratch on the lung dataset. Such performance gain is more pronounced with transfer learning or in the case of limited training data. Our methods also achieved comparable performance on other datasets. In addition, our methods achieved a substantial reduction in time consumption of training and inference compared with the 2.5D or 3D method.