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Objectives: Total tumor volume (TTV) is associated with overall and recurrence-free survival in patients with colorectal cancer liver metastases (CRLM). However, the labor-intensive nature of such manual assessments has hampered the clinical adoption of TTV as an imaging biomarker. This study aimed to develop and externally evaluate a CRLM auto-segmentation model on CT scans, to facilitate the clinical adoption of TTV., Methods: We developed an auto-segmentation model to segment CRLM using 783 contrast-enhanced portal venous phase CTs (CT-PVP) of 373 patients. We used a self-learning setup whereby we first trained a teacher model on 99 manually segmented CT-PVPs from three radiologists. The teacher model was then used to segment CRLM in the remaining 663 CT-PVPs for training the student model. We used the DICE score and the intraclass correlation coefficient (ICC) to compare the student model's segmentations and the TTV obtained from these segmentations to those obtained from the merged segmentations. We evaluated the student model in an external test set of 50 CT-PVPs from 35 patients from the Oslo University Hospital and an internal test set of 21 CT-PVPs from 10 patients from the Amsterdam University Medical Centers., Results: The model reached a mean DICE score of 0.85 (IQR: 0.05) and 0.83 (IQR: 0.10) on the internal and external test sets, respectively. The ICC between the segmented volumes from the student model and from the merged segmentations was 0.97 on both test sets., Conclusion: The developed colorectal cancer liver metastases auto-segmentation model achieved a high DICE score and near-perfect agreement for assessing TTV., Critical Relevance Statement: AI model segments colorectal liver metastases on CT with high performance on two test sets. Accurate segmentation of colorectal liver metastases could facilitate the clinical adoption of total tumor volume as an imaging biomarker for prognosis and treatment response monitoring., Key Points: Developed colorectal liver metastases segmentation model to facilitate total tumor volume assessment. Model achieved high performance on internal and external test sets. Model can improve prognostic stratification and treatment planning for colorectal liver metastases., Competing Interests: Declarations. Ethics approval and consent to participate: The Medical Ethics Review Committee of the Amsterdam UMC, the Regional Ethical Committee of Norway, and the Data Protection Officer of Oslo University Hospital approved this study protocol. All patients were managed per institutional practices. All patients signed a written informed consent form permitting the use of their data for studies. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Deformable image registration plays an important role in medical image analysis. Deep neural networks such as VoxelMorph and TransMorph are fast, but limited to small deformations and face challenges in the presence of large deformations. To tackle large deformations in medical image registration, we propose PC-Reg, a pyramidal Prediction and Correction method for deformable registration, which treats multi-scale registration akin to solving an ordinary differential equation (ODE) across scales. Starting with a zero-initialized deformation at the coarse level, PC-Reg follows the predictor-corrector regime and progressively predicts a residual flow and a correction flow to update the deformation vector field through different scales. The prediction in each scale can be regarded as a single step of ODE integration. PC-Reg can be easily extended to diffeomorphic registration and is able to alleviate the multiscale accumulated upsampling and diffeomorphic integration error. Further, to transfer details from full resolution to low scale, we introduce a distillation loss, where the output is used as the target label for intermediate outputs. Experiments on inter-patient deformable registration show that the proposed method significantly improves registration not only for large but also for small deformations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Efstratios Gavves reports financial support was provided by Elekta AB. Efstratios Gavves reports financial support was provided by University of Amsterdam. Jan Jakob Sonke reports a relationship with Elekta AB that includes: funding grants. Wenzhe Yin reports a relationship with University of Amsterdam that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

CT perfusion imaging is important in the imaging workup of acute ischemic stroke for evaluating affected cerebral tissue. CT perfusion analysis software produces cerebral perfusion maps from commonly noisy spatio-temporal CT perfusion data. High levels of noise can influence the results of CT perfusion analysis, necessitating software tuning. This work proposes a novel approach for CT perfusion analysis that uses physics-informed learning, an optimization framework that is robust to noise. In particular, we propose SPPINN: Spatio-temporal Perfusion Physics-Informed Neural Network and research spatio-temporal physics-informed learning. SPPINN learns implicit neural representations of contrast attenuation in CT perfusion scans using the spatio-temporal coordinates of the data and employs these representations to estimate a continuous representation of the cerebral perfusion parameters. We validate the approach on simulated data to quantify perfusion parameter estimation performance. Furthermore, we apply the method to in-house patient data and the public Ischemic Stroke Lesion Segmentation 2018 benchmark data to assess the correspondence between the perfusion maps and reference standard infarct core segmentations. Our method achieves accurate perfusion parameter estimates even with high noise levels and differentiates healthy tissue from infarcted tissue. Moreover, SPPINN perfusion maps accurately correspond with reference standard infarct core segmentations. Hence, we show that using spatio-temporal physics-informed learning for cerebral perfusion estimation is accurate, even in noisy CT perfusion data. The code for this work is available at https://github.com/lucasdevries/SPPINN., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Henk A. Marquering reports a relationship with Nicolab that includes: equity or stocks. Charles B.L.M. Majoie reports a relationship with Nicolab that includes: equity or stocks., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

CT perfusion imaging is commonly used for infarct core quantification in acute ischemic stroke patients. The outcomes and perfusion maps of CT perfusion software, however, show many discrepancies between vendors. We aim to perform infarct core segmentation directly from CT perfusion source data using machine learning, excluding the need to use the perfusion maps from standard CT perfusion software. To this end, we present a symmetry-aware spatio-temporal segmentation model that encodes the micro-perfusion dynamics in the brain, while decoding a static segmentation map for infarct core assessment. Our proposed spatio-temporal PerfU-Net employs an attention module on the skip-connections to match the dimensions of the encoder and decoder. We train and evaluate the method on 94 and 62 scans, respectively, using the Ischemic Stroke Lesion Segmentation (ISLES) 2018 challenge data. We achieve state-of-the-art results compared to methods that only use CT perfusion source imaging with a Dice score of 0.46. We are almost on par with methods that use perfusion maps from third party software, whilst it is known that there is a large variation in these perfusion maps from various vendors. Moreover, we achieve improved performance compared to simple perfusion map analysis, which is used in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Henk A. Marquering reports a relationship with Nicolab that includes: equity or stocks. Charles B.L.M. Majoie reports a relationship with Nicolab that includes: equity or stocks., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following competing interests. E.G. and J.T. are shareholders of Ellogon.ai. H.M. Horlings received a consultation fee paid to the institute from Roche Diagnostics, outside the scope of the work described here. The other authors report no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Thrombus volume in posterior circulation stroke (PCS) has been associated with outcome, through recanalization. Manual thrombus segmentation is impractical for large scale analysis of image characteristics. Hence, in this study we develop the first automatic method for thrombus localization and segmentation on CT in patients with PCS. In this multi-center retrospective study, 187 patients with PCS from the MR CLEAN Registry were included. We developed a convolutional neural network (CNN) that segments thrombi and restricts the volume-of-interest (VOI) to the brainstem (Polar-UNet). Furthermore, we reduced false positive localization by removing small-volume objects, referred to as volume-based removal (VBR). Polar-UNet is benchmarked against a CNN that does not restrict the VOI (BL-UNet). Performance metrics included the intra-class correlation coefficient (ICC) between automated and manually segmented thrombus volumes, the thrombus localization precision and recall, and the Dice coefficient. The majority of the thrombi were localized. Without VBR, Polar-UNet achieved a thrombus localization recall of 0.82, versus 0.78 achieved by BL-UNet. This high recall was accompanied by a low precision of 0.14 and 0.09. VBR improved precision to 0.65 and 0.56 for Polar-UNet and BL-UNet, respectively, with a small reduction in recall to 0.75 and 0.69. The Dice coefficient achieved by Polar-UNet was 0.44, versus 0.38 achieved by BL-UNet with VBR. Both methods achieved ICCs of 0.41 (95% CI: 0.27-0.54). Restricting the VOI to the brainstem improved the thrombus localization precision, recall, and segmentation overlap compared to the benchmark. VBR improved thrombus localization precision but lowered recall.

Thrombus imaging characteristics are associated with treatment success and functional outcomes in stroke patients. However, assessing these characteristics based on manual annotations is labor intensive and subject to observer bias. Therefore, we aimed to create an automated pipeline for consistent and fast full thrombus segmentation. We used multi-center, multi-scanner datasets of anterior circulation stroke patients with baseline NCCT and CTA for training (n = 228) and testing (n = 100). We first found the occlusion location using StrokeViewer LVO and created a bounding box around it. Subsequently, we trained dual modality U-Net based convolutional neural networks (CNNs) to segment the thrombus inside this bounding box. We experimented with: (1) U-Net with two input channels for NCCT and CTA, and U-Nets with two encoders where (2) concatenate, (3) add, and (4) weighted-sum operators were used for feature fusion. Furthermore, we proposed a dynamic bounding box algorithm to adjust the bounding box. The dynamic bounding box algorithm reduces the missed cases but does not improve Dice. The two-encoder U-Net with a weighted-sum feature fusion shows the best performance (surface Dice 0.78, Dice 0.62, and 4% missed cases). Final segmentation results have high spatial accuracies and can therefore be used to determine thrombus characteristics and potentially benefit radiologists in clinical practice.

Background and Objectives: Transfer learning is a valuable approach to perform medical image segmentation in settings with limited cases available for training convolutional neural networks (CNN). Both the source task and the source domain influence transfer learning performance on a given target medical image segmentation task. This study aims to assess transfer learning-based medical segmentation task performance for various source task and domain combinations., Methods: CNNs were pre-trained on classification, segmentation, and self-supervised tasks on two domains: natural images and T1 brain MRI. Next, these CNNs were fine-tuned on three target T1 brain MRI segmentation tasks: stroke lesion, MS lesions, and brain anatomy segmentation. In all experiments, the CNN architecture and transfer learning strategy were the same. The segmentation accuracy on all target tasks was evaluated using the mIOU or Dice coefficients. The detection accuracy was evaluated for the stroke and MS lesion target tasks only., Results: CNNs pre-trained on a segmentation task on the same domain as the target tasks resulted in higher or similar segmentation accuracy compared to other source task and domain combinations. Pre-training a CNN on ImageNet resulted in a comparable, but not consistently higher lesion detection rate, despite the amount of training data used being 10 times larger., Conclusions: This study suggests that optimal transfer learning for medical segmentation is achieved with a similar task and domain for pre-training. As a result, CNNs can be effectively pre-trained on smaller datasets by selecting a source domain and task similar to the target domain and task., Competing Interests: Declaration of Competing Interest This publication is based on the STAIRS project under the TKI-PPP program. The collaboration project is co-funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. Dr. H.A. Marquering is a cofounder and shareholder of Nico.Lab. Dr. M.W.A. Caan is shareholder of Nico.Lab., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Final lesion volume (FLV) is a surrogate outcome measure in anterior circulation stroke (ACS). In posterior circulation stroke (PCS), this relation is plausibly understudied due to a lack of methods that automatically quantify FLV. The applicability of deep learning approaches to PCS is limited due to its lower incidence compared to ACS. We evaluated strategies to develop a convolutional neural network (CNN) for PCS lesion segmentation by using image data from both ACS and PCS patients. We included follow-up non-contrast computed tomography scans of 1018 patients with ACS and 107 patients with PCS. To assess whether an ACS lesion segmentation generalizes to PCS, a CNN was trained on ACS data (ACS-CNN). Second, to evaluate the performance of only including PCS patients, a CNN was trained on PCS data. Third, to evaluate the performance when combining the datasets, a CNN was trained on both datasets. Finally, to evaluate the performance of transfer learning, the ACS-CNN was fine-tuned using PCS patients. The transfer learning strategy outperformed the other strategies in volume agreement with an intra-class correlation of 0.88 (95% CI: 0.83-0.92) vs. 0.55 to 0.83 and a lesion detection rate of 87% vs. 41-77 for the other strategies. Hence, transfer learning improved the FLV quantification and detection rate of PCS lesions compared to the other strategies.

The goal of this paper is guided image filtering, which emphasizes the importance of structure transfer during filtering by means of an additional guidance image. Where classical guided filters transfer structures using hand-designed functions, recent guided filters have been considerably advanced through parametric learning of deep networks. The state-of-the-art leverages deep networks to estimate the two core coefficients of the guided filter. In this work, we posit that simultaneously estimating both coefficients is suboptimal, resulting in halo artifacts and structure inconsistencies. Inspired by unsharp masking, a classical technique for edge enhancement that requires only a single coefficient, we propose a new and simplified formulation of the guided filter. Our formulation enjoys a filtering prior from a low-pass filter and enables explicit structure transfer by estimating a single coefficient. Based on our proposed formulation, we introduce a successive guided filtering network, which provides multiple filtering results from a single network, allowing for a trade-off between accuracy and efficiency. Extensive ablations, comparisons and analysis show the effectiveness and efficiency of our formulation and network, resulting in state-of-the-art results across filtering tasks like upsampling, denoising, and cross-modality filtering. Code is available at https://github.com/shizenglin/Unsharp-Mask-Guided-Filtering.

BACKGROUND The correct interpretation of the ECG is pivotal for the accurate diagnosis of many cardiac abnormalities, and conventional computerized interpretation has not been able to reach physician-level accuracy in detecting (acute) cardiac abnormalities. This study aims to develop and validate a deep neural network for comprehensive automated ECG triage in daily practice. METHODS AND RESULTS We developed a 37-layer convolutional residual deep neural network on a data set of free-text physician-annotated 12-lead ECGs. The deep neural network was trained on a data set with 336.835 recordings from 142.040 patients and validated on an independent validation data set (n=984), annotated by a panel of 5 cardiologists electrophysiologists. The 12-lead ECGs were acquired in all noncardiology departments of the University Medical Center Utrecht. The algorithm learned to classify these ECGs into the following 4 triage categories: normal, abnormal not acute, subacute, and acute. Discriminative performance is presented with overall and category-specific concordance statistics, polytomous discrimination indexes, sensitivities, specificities, and positive and negative predictive values. The patients in the validation data set had a mean age of 60.4 years and 54.3% were men. The deep neural network showed excellent overall discrimination with an overall concordance statistic of 0.93 (95% CI, 0.92-0.95) and a polytomous discriminatory index of 0.83 (95% CI, 0.79-0.87). CONCLUSIONS This study demonstrates that an end-to-end deep neural network can be accurately trained on unstructured free-text physician annotations and used to consistently triage 12-lead ECGs. When further fine-tuned with other clinical outcomes and externally validated in clinical practice, the demonstrated deep learning-based ECG interpretation can potentially improve time to treatment and decrease healthcare burden.

We introduce the concept of dynamic image, a novel compact representation of videos useful for video analysis, particularly in combination with convolutional neural networks (CNNs). A dynamic image encodes temporal data such as RGB or optical flow videos by using the concept of 'rank pooling'. The idea is to learn a ranking machine that captures the temporal evolution of the data and to use the parameters of the latter as a representation. We call the resulting representation dynamic image because it summarizes the video dynamics in addition to appearance. This powerful idea allows to convert any video to an image so that existing CNN models pre-trained with still images can be immediately extended to videos. We also present an efficient approximate rank pooling operator that runs two orders of magnitude faster than the standard ones with any loss in ranking performance and can be formulated as a CNN layer. To demonstrate the power of the representation, we introduce a novel four stream CNN architecture which can learn from RGB and optical flow frames as well as from their dynamic image representations. We show that the proposed network achieves state-of-the-art performance, 95.5 and 72.5 percent accuracy, in the UCF101 and HMDB51, respectively.

In this paper, we present a method that estimates reflectance and illumination information from a single image depicting a single-material specular object from a given class under natural illumination. We follow a data-driven, learning-based approach trained on a very large dataset, but in contrast to earlier work we do not assume one or more components (shape, reflectance, or illumination) to be known. We propose a two-step approach, where we first estimate the object's reflectance map, and then further decompose it into reflectance and illumination. For the first step, we introduce a Convolutional Neural Network (CNN) that directly predicts a reflectance map from the input image itself, as well as an indirect scheme that uses additional supervision, first estimating surface orientation and afterwards inferring the reflectance map using a learning-based sparse data interpolation technique. For the second step, we suggest a CNN architecture to reconstruct both Phong reflectance parameters and high-resolution spherical illumination maps from the reflectance map. We also propose new datasets to train these CNNs. We demonstrate the effectiveness of our approach for both steps by extensive quantitative and qualitative evaluation in both synthetic and real data as well as through numerous applications, that show improvements over the state-of-the-art.

We propose a function-based temporal pooling method that captures the latent structure of the video sequence data - e.g., how frame-level features evolve over time in a video. We show how the parameters of a function that has been fit to the video data can serve as a robust new video representation. As a specific example, we learn a pooling function via ranking machines. By learning to rank the frame-level features of a video in chronological order, we obtain a new representation that captures the video-wide temporal dynamics of a video, suitable for action recognition. Other than ranking functions, we explore different parametric models that could also explain the temporal changes in videos. The proposed functional pooling methods, and rank pooling in particular, is easy to interpret and implement, fast to compute and effective in recognizing a wide variety of actions. We evaluate our method on various benchmarks for generic action, fine-grained action and gesture recognition. Results show that rank pooling brings an absolute improvement of 7-10 average pooling baseline. At the same time, rank pooling is compatible with and complementary to several appearance and local motion based methods and features, such as improved trajectories and deep learning features.