arXiv subjects

Josien P. W. Pluim

Publications and source records attributed to Josien P. W. Pluim.

At least 37 records · Page 2Linked to original sources

arXiv2022

Influence of uncertainty estimation techniques on false-positive reduction in liver lesion detection

Deep learning techniques show success in detecting objects in medical images, but still suffer from false-positive predictions that may hinder accurate diagnosis. The estimated uncertainty of the neural network output has been used to flag incorrect predictions. We study the role played by features computed from neural network uncertainty estimates and shape-based features computed from binary predictions in reducing false positives in liver lesion detection by developing a classification-based post-processing step for different uncertainty estimation methods. We demonstrate an improvement in the lesion detection performance of the neural network (with respect to F1-score) for all uncertainty estimation methods on two datasets, comprising abdominal MR and CT images, respectively. We show that features computed from neural network uncertainty estimates tend not to contribute much toward reducing false positives. Our results show that factors like class imbalance (true over false positive ratio) and shape-based features extracted from uncertainty maps play an important role in distinguishing false positive from true positive predictions. Our code can be found at https://github.com/ishaanb92/FPCPipeline.

eess.IV↗

arXiv2022

Generalized Probabilistic U-Net for medical image segementation

We propose the Generalized Probabilistic U-Net, which extends the Probabilistic U-Net by allowing more general forms of the Gaussian distribution as the latent space distribution that can better approximate the uncertainty in the reference segmentations. We study the effect the choice of latent space distribution has on capturing the uncertainty in the reference segmentations using the LIDC-IDRI dataset. We show that the choice of distribution affects the sample diversity of the predictions and their overlap with respect to the reference segmentations. For the LIDC-IDRI dataset, we show that using a mixture of Gaussians results in a statistically significant improvement in the generalized energy distance (GED) metric with respect to the standard Probabilistic U-Net. We have made our implementation available at https://github.com/ishaanb92/GeneralizedProbabilisticUNet

cs.CV↗

arXiv2022

clDice -- A Novel Topology-Preserving Loss Function for Tubular Structure Segmentation

Accurate segmentation of tubular, network-like structures, such as vessels, neurons, or roads, is relevant to many fields of research. For such structures, the topology is their most important characteristic; particularly preserving connectedness: in the case of vascular networks, missing a connected vessel entirely alters the blood-flow dynamics. We introduce a novel similarity measure termed centerlineDice (short clDice), which is calculated on the intersection of the segmentation masks and their (morphological) skeleta. We theoretically prove that clDice guarantees topology preservation up to homotopy equivalence for binary 2D and 3D segmentation. Extending this, we propose a computationally efficient, differentiable loss function (soft-clDice) for training arbitrary neural segmentation networks. We benchmark the soft-clDice loss on five public datasets, including vessels, roads and neurons (2D and 3D). Training on soft-clDice leads to segmentation with more accurate connectivity information, higher graph similarity, and better volumetric scores.

cs.CV↗

arXiv2021

ENHANCE (ENriching Health data by ANnotations of Crowd and Experts): A case study for skin lesion classification

We present ENHANCE, an open dataset with multiple annotations to complement the existing ISIC and PH2 skin lesion classification datasets. This dataset contains annotations of visual ABC (asymmetry, border, colour) features from non-expert annotation sources: undergraduate students, crowd workers from Amazon MTurk and classic image processing algorithms. In this paper we first analyse the correlations between the annotations and the diagnostic label of the lesion, as well as study the agreement between different annotation sources. Overall we find weak correlations of non-expert annotations with the diagnostic label, and low agreement between different annotation sources. We then study multi-task learning (MTL) with the annotations as additional labels, and show that non-expert annotations can improve (ensembles of) state-of-the-art convolutional neural networks via MTL. We hope that our dataset can be used in further research into multiple annotations and/or MTL. All data and models are available on Github: https://github.com/raumannsr/ENHANCE.

cs.CV↗

arXiv2021

Adversarial Attack Vulnerability of Medical Image Analysis Systems: Unexplored Factors

Adversarial attacks are considered a potentially serious security threat for machine learning systems. Medical image analysis (MedIA) systems have recently been argued to be vulnerable to adversarial attacks due to strong financial incentives and the associated technological infrastructure. In this paper, we study previously unexplored factors affecting adversarial attack vulnerability of deep learning MedIA systems in three medical domains: ophthalmology, radiology, and pathology. We focus on adversarial black-box settings, in which the attacker does not have full access to the target model and usually uses another model, commonly referred to as surrogate model, to craft adversarial examples. We consider this to be the most realistic scenario for MedIA systems. Firstly, we study the effect of weight initialization (ImageNet vs. random) on the transferability of adversarial attacks from the surrogate model to the target model. Secondly, we study the influence of differences in development data between target and surrogate models. We further study the interaction of weight initialization and data differences with differences in model architecture. All experiments were done with a perturbation degree tuned to ensure maximal transferability at minimal visual perceptibility of the attacks. Our experiments show that pre-training may dramatically increase the transferability of adversarial examples, even when the target and surrogate's architectures are different: the larger the performance gain using pre-training, the larger the transferability. Differences in the development data between target and surrogate models considerably decrease the performance of the attack; this decrease is further amplified by difference in the model architecture. We believe these factors should be considered when developing security-critical MedIA systems planned to be deployed in clinical practice.

cs.CR↗

arXiv2021

Corneal Pachymetry by AS-OCT after Descemet's Membrane Endothelial Keratoplasty

Corneal thickness (pachymetry) maps can be used to monitor restoration of corneal endothelial function, for example after Descemet's membrane endothelial keratoplasty (DMEK). Automated delineation of the corneal interfaces in anterior segment optical coherence tomography (AS-OCT) can be challenging for corneas that are irregularly shaped due to pathology, or as a consequence of surgery, leading to incorrect thickness measurements. In this research, deep learning is used to automatically delineate the corneal interfaces and measure corneal thickness with high accuracy in post-DMEK AS-OCT B-scans. Three different deep learning strategies were developed based on 960 B-scans from 50 patients. On an independent test set of 320 B-scans, corneal thickness could be measured with an error of 13.98 to 15.50 micrometer for the central 9 mm range, which is less than 3% of the average corneal thickness. The accurate thickness measurements were used to construct detailed pachymetry maps. Moreover, follow-up scans could be registered based on anatomical landmarks to obtain differential pachymetry maps. These maps may enable a more comprehensive understanding of the restoration of the endothelial function after DMEK, where thickness often varies throughout different regions of the cornea, and subsequently contribute to a standardized postoperative regime.

physics.med-ph↗

arXiv2021

Using uncertainty estimation to reduce false positives in liver lesion detection

Despite the successes of deep learning techniques at detecting objects in medical images, false positive detections occur which may hinder an accurate diagnosis. We propose a technique to reduce false positive detections made by a neural network using an SVM classifier trained with features derived from the uncertainty map of the neural network prediction. We demonstrate the effectiveness of this method for the detection of liver lesions on a dataset of abdominal MR images. We find that the use of a dropout rate of 0.5 produces the least number of false positives in the neural network predictions and the trained classifier filters out approximately 90% of these false positives detections in the test-set.

eess.IV↗

arXiv2020

Deep Learning-Based Grading of Ductal Carcinoma In Situ in Breast Histopathology Images

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that can progress into invasive ductal carcinoma (IDC). Studies suggest DCIS is often overtreated since a considerable part of DCIS lesions may never progress into IDC. Lower grade lesions have a lower progression speed and risk, possibly allowing treatment de-escalation. However, studies show significant inter-observer variation in DCIS grading. Automated image analysis may provide an objective solution to address high subjectivity of DCIS grading by pathologists. In this study, we developed a deep learning-based DCIS grading system. It was developed using the consensus DCIS grade of three expert observers on a dataset of 1186 DCIS lesions from 59 patients. The inter-observer agreement, measured by quadratic weighted Cohen's kappa, was used to evaluate the system and compare its performance to that of expert observers. We present an analysis of the lesion-level and patient-level inter-observer agreement on an independent test set of 1001 lesions from 50 patients. The deep learning system (dl) achieved on average slightly higher inter-observer agreement to the observers (o1, o2 and o3) ($κ_{o1,dl}=0.81, κ_{o2,dl}=0.53, κ_{o3,dl}=0.40$) than the observers amongst each other ($κ_{o1,o2}=0.58, κ_{o1,o3}=0.50, κ_{o2,o3}=0.42$) at the lesion-level. At the patient-level, the deep learning system achieved similar agreement to the observers ($κ_{o1,dl}=0.77, κ_{o2,dl}=0.75, κ_{o3,dl}=0.70$) as the observers amongst each other ($κ_{o1,o2}=0.77, κ_{o1,o3}=0.75, κ_{o2,o3}=0.72$). In conclusion, we developed a deep learning-based DCIS grading system that achieved a performance similar to expert observers. We believe this is the first automated system that could assist pathologists by providing robust and reproducible second opinions on DCIS grade.

eess.IV↗

arXiv2020

Orientation-Disentangled Unsupervised Representation Learning for Computational Pathology

Unsupervised learning enables modeling complex images without the need for annotations. The representation learned by such models can facilitate any subsequent analysis of large image datasets. However, some generative factors that cause irrelevant variations in images can potentially get entangled in such a learned representation causing the risk of negatively affecting any subsequent use. The orientation of imaged objects, for instance, is often arbitrary/irrelevant, thus it can be desired to learn a representation in which the orientation information is disentangled from all other factors. Here, we propose to extend the Variational Auto-Encoder framework by leveraging the group structure of rotation-equivariant convolutional networks to learn orientation-wise disentangled generative factors of histopathology images. This way, we enforce a novel partitioning of the latent space, such that oriented and isotropic components get separated. We evaluated this structured representation on a dataset that consists of tissue regions for which nuclear pleomorphism and mitotic activity was assessed by expert pathologists. We show that the trained models efficiently disentangle the inherent orientation information of single-cell images. In comparison to classical approaches, the resulting aggregated representation of sub-populations of cells produces higher performances in subsequent tasks.

eess.IV↗

arXiv2020

Primary Tumor Origin Classification of Lung Nodules in Spectral CT using Transfer Learning

Early detection of lung cancer has been proven to decrease mortality significantly. A recent development in computed tomography (CT), spectral CT, can potentially improve diagnostic accuracy, as it yields more information per scan than regular CT. However, the shear workload involved with analyzing a large number of scans drives the need for automated diagnosis methods. Therefore, we propose a detection and classification system for lung nodules in CT scans. Furthermore, we want to observe whether spectral images can increase classifier performance. For the detection of nodules we trained a VGG-like 3D convolutional neural net (CNN). To obtain a primary tumor classifier for our dataset we pre-trained a 3D CNN with similar architecture on nodule malignancies of a large publicly available dataset, the LIDC-IDRI dataset. Subsequently we used this pre-trained network as feature extractor for the nodules in our dataset. The resulting feature vectors were classified into two (benign/malignant) and three (benign/primary lung cancer/metastases) classes using support vector machine (SVM). This classification was performed both on nodule- and scan-level. We obtained state-of-the art performance for detection and malignancy regression on the LIDC-IDRI database. Classification performance on our own dataset was higher for scan- than for nodule-level predictions. For the three-class scan-level classification we obtained an accuracy of 78\%. Spectral features did increase classifier performance, but not significantly. Our work suggests that a pre-trained feature extractor can be used as primary tumor origin classifier for lung nodules, eliminating the need for elaborate fine-tuning of a new network and large datasets. Code is available at \url{https://github.com/tueimage/lung-nodule-msc-2018}.

cs.CV↗

arXiv2020

Quantifying Graft Detachment after Descemet's Membrane Endothelial Keratoplasty with Deep Convolutional Neural Networks

Purpose: We developed a method to automatically locate and quantify graft detachment after Descemet's Membrane Endothelial Keratoplasty (DMEK) in Anterior Segment Optical Coherence Tomography (AS-OCT) scans. Methods: 1280 AS-OCT B-scans were annotated by a DMEK expert. Using the annotations, a deep learning pipeline was developed to localize scleral spur, center the AS-OCT B-scans and segment the detached graft sections. Detachment segmentation model performance was evaluated per B-scan by comparing (1) length of detachment and (2) horizontal projection of the detached sections with the expert annotations. Horizontal projections were used to construct graft detachment maps. All final evaluations were done on a test set that was set apart during training of the models. A second DMEK expert annotated the test set to determine inter-rater performance. Results: Mean scleral spur localization error was 0.155 mm, whereas the inter-rater difference was 0.090 mm. The estimated graft detachment lengths were in 69% of the cases within a 10-pixel (~150μm) difference from the ground truth (77% for the second DMEK expert). Dice scores for the horizontal projections of all B-scans with detachments were 0.896 and 0.880 for our model and the second DMEK expert respectively. Conclusion: Our deep learning model can be used to automatically and instantly localize graft detachment in AS-OCT B-scans. Horizontal detachment projections can be determined with the same accuracy as a human DMEK expert, allowing for the construction of accurate graft detachment maps. Translational Relevance: Automated localization and quantification of graft detachment can support DMEK research and standardize clinical decision making.

eess.IV↗

arXiv2020

Roto-Translation Equivariant Convolutional Networks: Application to Histopathology Image Analysis

Rotation-invariance is a desired property of machine-learning models for medical image analysis and in particular for computational pathology applications. We propose a framework to encode the geometric structure of the special Euclidean motion group SE(2) in convolutional networks to yield translation and rotation equivariance via the introduction of SE(2)-group convolution layers. This structure enables models to learn feature representations with a discretized orientation dimension that guarantees that their outputs are invariant under a discrete set of rotations. Conventional approaches for rotation invariance rely mostly on data augmentation, but this does not guarantee the robustness of the output when the input is rotated. At that, trained conventional CNNs may require test-time rotation augmentation to reach their full capability. This study is focused on histopathology image analysis applications for which it is desirable that the arbitrary global orientation information of the imaged tissues is not captured by the machine learning models. The proposed framework is evaluated on three different histopathology image analysis tasks (mitosis detection, nuclei segmentation and tumor classification). We present a comparative analysis for each problem and show that consistent increase of performances can be achieved when using the proposed framework.

cs.CV↗

arXiv2019

Direct Classification of Type 2 Diabetes From Retinal Fundus Images in a Population-based Sample From The Maastricht Study

Type 2 Diabetes (T2D) is a chronic metabolic disorder that can lead to blindness and cardiovascular disease. Information about early stage T2D might be present in retinal fundus images, but to what extent these images can be used for a screening setting is still unknown. In this study, deep neural networks were employed to differentiate between fundus images from individuals with and without T2D. We investigated three methods to achieve high classification performance, measured by the area under the receiver operating curve (ROC-AUC). A multi-target learning approach to simultaneously output retinal biomarkers as well as T2D works best (AUC = 0.746 [$\pm$0.001]). Furthermore, the classification performance can be improved when images with high prediction uncertainty are referred to a specialist. We also show that the combination of images of the left and right eye per individual can further improve the classification performance (AUC = 0.758 [$\pm$0.003]), using a simple averaging approach. The results are promising, suggesting the feasibility of screening for T2D from retinal fundus images.

eess.IV↗

arXiv2019

Patient-specific fine-tuning of CNNs for follow-up lesion quantification

Convolutional neural network (CNN) methods have been proposed to quantify lesions in medical imaging. Commonly more than one imaging examination is available for a patient, but the serial information in these images often remains unused. CNN-based methods have the potential to extract valuable information from previously acquired imaging to better quantify current imaging of the same patient. A pre-trained CNN can be updated with a patient's previously acquired imaging: patient-specific fine-tuning. In this work, we studied the improvement in performance of lesion quantification methods on MR images after fine-tuning compared to a base CNN. We applied the method to two different approaches: the detection of liver metastases and the segmentation of brain white matter hyperintensities (WMH). The patient-specific fine-tuned CNN has a better performance than the base CNN. For the liver metastases, the median true positive rate increases from 0.67 to 0.85. For the WMH segmentation, the mean Dice similarity coefficient increases from 0.82 to 0.87. In this study we showed that patient-specific fine-tuning has potential to improve the lesion quantification performance of general CNNs by exploiting the patient's previously acquired imaging.

eess.IV↗

arXiv2019

Liver segmentation and metastases detection in MR images using convolutional neural networks

Primary tumors have a high likelihood of developing metastases in the liver and early detection of these metastases is crucial for patient outcome. We propose a method based on convolutional neural networks (CNN) to detect liver metastases. First, the liver was automatically segmented using the six phases of abdominal dynamic contrast enhanced (DCE) MR images. Next, DCE-MR and diffusion weighted (DW) MR images are used for metastases detection within the liver mask. The liver segmentations have a median Dice similarity coefficient of 0.95 compared with manual annotations. The metastases detection method has a sensitivity of 99.8% with a median of 2 false positives per image. The combination of the two MR sequences in a dual pathway network is proven valuable for the detection of liver metastases. In conclusion, a high quality liver segmentation can be obtained in which we can successfully detect liver metastases.

eess.IV↗

arXiv2019

Motion correction of dynamic contrast enhanced MRI of the liver

Motion correction of dynamic contrast enhanced magnetic resonance images (DCE-MRI) is a challenging task, due to changes in image appearance. In this study a groupwise registration, using a principle component analysis (PCA) based metric,1 is evaluated for clinical DCE MRI of the liver. The groupwise registration transforms the images to a common space, rather than to a reference volume as conventional pairwise methods do, and computes the similarity metric on all volumes simultaneously. This groupwise registration method is compared to a pairwise approach using a mutual information metric. Clinical DCE MRI of the abdomen of eight patients were included. Per patient one lesion in the liver was manually segmented in all temporal images (N=16). The registered images were compared for accuracy, spatial and temporal smoothness after transformation, and lesion volume change. Compared to a pairwise method or no registration, groupwise registration provided better alignment. In our recently started clinical study groupwise registered clinical DCE MRI of the abdomen of nine patients were scored by three radiologists. Groupwise registration increased the assessed quality of alignment. The gain in reading time for the radiologist was estimated to vary from no difference to almost a minute. A slight increase in reader confidence was also observed. Registration had no added value for images with little motion. In conclusion, the groupwise registration of DCE MR images results in better alignment than achieved by pairwise registration, which is beneficial for clinical assessment.

eess.IV↗

arXiv2019

Optimal input configuration of dynamic contrast enhanced MRI in convolutional neural networks for liver segmentation

Most MRI liver segmentation methods use a structural 3D scan as input, such as a T1 or T2 weighted scan. Segmentation performance may be improved by utilizing both structural and functional information, as contained in dynamic contrast enhanced (DCE) MR series. Dynamic information can be incorporated in a segmentation method based on convolutional neural networks in a number of ways. In this study, the optimal input configuration of DCE MR images for convolutional neural networks (CNNs) is studied. The performance of three different input configurations for CNNs is studied for a liver segmentation task. The three configurations are I) one phase image of the DCE-MR series as input image; II) the separate phases of the DCE-MR as input images; and III) the separate phases of the DCE-MR as channels of one input image. The three input configurations are fed into a dilated fully convolutional network and into a small U-net. The CNNs were trained using 19 annotated DCE-MR series and tested on another 19 annotated DCE-MR series. The performance of the three input configurations for both networks is evaluated against manual annotations. The results show that both neural networks perform better when the separate phases of the DCE-MR series are used as channels of an input image in comparison to one phase as input image or the separate phases as input images. No significant difference between the performances of the two network architectures was found for the separate phases as channels of an input image.

eess.IV↗

arXiv2019

Predicting breast tumor proliferation from whole-slide images: the TUPAC16 challenge

Tumor proliferation is an important biomarker indicative of the prognosis of breast cancer patients. Assessment of tumor proliferation in a clinical setting is highly subjective and labor-intensive task. Previous efforts to automate tumor proliferation assessment by image analysis only focused on mitosis detection in predefined tumor regions. However, in a real-world scenario, automatic mitosis detection should be performed in whole-slide images (WSIs) and an automatic method should be able to produce a tumor proliferation score given a WSI as input. To address this, we organized the TUmor Proliferation Assessment Challenge 2016 (TUPAC16) on prediction of tumor proliferation scores from WSIs. The challenge dataset consisted of 500 training and 321 testing breast cancer histopathology WSIs. In order to ensure fair and independent evaluation, only the ground truth for the training dataset was provided to the challenge participants. The first task of the challenge was to predict mitotic scores, i.e., to reproduce the manual method of assessing tumor proliferation by a pathologist. The second task was to predict the gene expression based PAM50 proliferation scores from the WSI. The best performing automatic method for the first task achieved a quadratic-weighted Cohen's kappa score of $κ$ = 0.567, 95% CI [0.464, 0.671] between the predicted scores and the ground truth. For the second task, the predictions of the top method had a Spearman's correlation coefficient of r = 0.617, 95% CI [0.581 0.651] with the ground truth. This was the first study that investigated tumor proliferation assessment from WSIs. The achieved results are promising given the difficulty of the tasks and weakly-labelled nature of the ground truth. However, further research is needed to improve the practical utility of image analysis methods for this task.

cs.CV↗