arXiv subjects

Stefan Klein

Publications and source records attributed to Stefan Klein.

At least 37 records · Page 2Linked to original sources

arXiv2024

Evaluating the Fairness of Neural Collapse in Medical Image Classification

Deep learning has achieved impressive performance across various medical imaging tasks. However, its inherent bias against specific groups hinders its clinical applicability in equitable healthcare systems. A recently discovered phenomenon, Neural Collapse (NC), has shown potential in improving the generalization of state-of-the-art deep learning models. Nonetheless, its implications on bias in medical imaging remain unexplored. Our study investigates deep learning fairness through the lens of NC. We analyze the training dynamics of models as they approach NC when training using biased datasets, and examine the subsequent impact on test performance, specifically focusing on label bias. We find that biased training initially results in different NC configurations across subgroups, before converging to a final NC solution by memorizing all data samples. Through extensive experiments on three medical imaging datasets -- PAPILA, HAM10000, and CheXpert -- we find that in biased settings, NC can lead to a significant drop in F1 score across all subgroups. Our code is available at https://gitlab.com/radiology/neuro/neural-collapse-fairness

cs.CV↗

arXiv2024

Minimally Interactive Segmentation of Soft-Tissue Tumors on CT and MRI using Deep Learning

Segmentations are crucial in medical imaging to obtain morphological, volumetric, and radiomics biomarkers. Manual segmentation is accurate but not feasible in the radiologist's clinical workflow, while automatic segmentation generally obtains sub-par performance. We therefore developed a minimally interactive deep learning-based segmentation method for soft-tissue tumors (STTs) on CT and MRI. The method requires the user to click six points near the tumor's extreme boundaries. These six points are transformed into a distance map and serve, with the image, as input for a Convolutional Neural Network. For training and validation, a multicenter dataset containing 514 patients and nine STT types in seven anatomical locations was used, resulting in a Dice Similarity Coefficient (DSC) of 0.85$\pm$0.11 (mean $\pm$ standard deviation (SD)) for CT and 0.84$\pm$0.12 for T1-weighted MRI, when compared to manual segmentations made by expert radiologists. Next, the method was externally validated on a dataset including five unseen STT phenotypes in extremities, achieving 0.81$\pm$0.08 for CT, 0.84$\pm$0.09 for T1-weighted MRI, and 0.88\pm0.08 for previously unseen T2-weighted fat-saturated (FS) MRI. In conclusion, our minimally interactive segmentation method effectively segments different types of STTs on CT and MRI, with robust generalization to previously unseen phenotypes and imaging modalities.

eess.IV↗

arXiv2023

An Interpretable Machine Learning Model with Deep Learning-based Imaging Biomarkers for Diagnosis of Alzheimer's Disease

Machine learning methods have shown large potential for the automatic early diagnosis of Alzheimer's Disease (AD). However, some machine learning methods based on imaging data have poor interpretability because it is usually unclear how they make their decisions. Explainable Boosting Machines (EBMs) are interpretable machine learning models based on the statistical framework of generalized additive modeling, but have so far only been used for tabular data. Therefore, we propose a framework that combines the strength of EBM with high-dimensional imaging data using deep learning-based feature extraction. The proposed framework is interpretable because it provides the importance of each feature. We validated the proposed framework on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, achieving accuracy of 0.883 and area-under-the-curve (AUC) of 0.970 on AD and control classification. Furthermore, we validated the proposed framework on an external testing set, achieving accuracy of 0.778 and AUC of 0.887 on AD and subjective cognitive decline (SCD) classification. The proposed framework significantly outperformed an EBM model using volume biomarkers instead of deep learning-based features, as well as an end-to-end convolutional neural network (CNN) with optimized architecture.

eess.IV↗

arXiv2023

Comparison of retinal regions-of-interest imaged by OCT for the classification of intermediate AMD

To study whether it is possible to differentiate intermediate age-related macular degeneration (AMD) from healthy controls using partial optical coherence tomography (OCT) data, that is, restricting the input B-scans to certain pre-defined regions of interest (ROIs). A total of 15744 B-scans from 269 intermediate AMD patients and 115 normal subjects were used in this study (split on subject level in 80% train, 10% validation and 10% test). From each OCT B-scan, three ROIs were extracted: retina, complex between retinal pigment epithelium (RPE) and Bruch membrane (BM), and choroid (CHO). These ROIs were obtained using two different methods: masking and cropping. In addition to the six ROIs, the whole OCT B-scan and the binary mask corresponding to the segmentation of the RPE-BM complex were used. For each subset, a convolutional neural network (based on VGG16 architecture and pre-trained on ImageNet) was trained and tested. The performance of the models was evaluated using the area under the receiver operating characteristic (AUROC), accuracy, sensitivity, and specificity. All trained models presented an AUROC, accuracy, sensitivity, and specificity equal to or higher than 0.884, 0.816, 0.685, and 0.644, respectively. The model trained on the whole OCT B-scan presented the best performance (AUROC = 0.983, accuracy = 0.927, sensitivity = 0.862, specificity = 0.913). The models trained on the ROIs obtained with the cropping method led to significantly higher outcomes than those obtained with masking, with the exception of the retinal tissue, where no statistically significant difference was observed between cropping and masking (p = 0.47). This study demonstrated that while using the complete OCT B-scan provided the highest accuracy in classifying intermediate AMD, models trained on specific ROIs such as the RPE-BM complex or the choroid can still achieve high performance.

eess.IV↗

arXiv2022

Data synthesis and adversarial networks: A review and meta-analysis in cancer imaging

Despite technological and medical advances, the detection, interpretation, and treatment of cancer based on imaging data continue to pose significant challenges. These include inter-observer variability, class imbalance, dataset shifts, inter- and intra-tumour heterogeneity, malignancy determination, and treatment effect uncertainty. Given the recent advancements in Generative Adversarial Networks (GANs), data synthesis, and adversarial training, we assess the potential of these technologies to address a number of key challenges of cancer imaging. We categorise these challenges into (a) data scarcity and imbalance, (b) data access and privacy, (c) data annotation and segmentation, (d) cancer detection and diagnosis, and (e) tumour profiling, treatment planning and monitoring. Based on our analysis of 164 publications that apply adversarial training techniques in the context of cancer imaging, we highlight multiple underexplored solutions with research potential. We further contribute the Synthesis Study Trustworthiness Test (SynTRUST), a meta-analysis framework for assessing the validation rigour of medical image synthesis studies. SynTRUST is based on 26 concrete measures of thoroughness, reproducibility, usefulness, scalability, and tenability. Based on SynTRUST, we analyse 16 of the most promising cancer imaging challenge solutions and observe a high validation rigour in general, but also several desirable improvements. With this work, we strive to bridge the gap between the needs of the clinical cancer imaging community and the current and prospective research on data synthesis and adversarial networks in the artificial intelligence community.

eess.IV↗

arXiv2022

Computer-aided diagnosis and prediction in brain disorders

Computer-aided methods have shown added value for diagnosing and predicting brain disorders and can thus support decision making in clinical care and treatment planning. This chapter will provide insight into the type of methods, their working, their input data - such as cognitive tests, imaging and genetic data - and the types of output they provide. We will focus on specific use cases for diagnosis, i.e. estimating the current 'condition' of the patient, such as early detection and diagnosis of dementia, differential diagnosis of brain tumours, and decision making in stroke. Regarding prediction, i.e. estimation of the future 'condition' of the patient, we will zoom in on use cases such as predicting the disease course in multiple sclerosis and predicting patient outcomes after treatment in brain cancer. Furthermore, based on these use cases, we will assess the current state-of-the-art methodology and highlight current efforts on benchmarking of these methods and the importance of open science therein. Finally, we assess the current clinical impact of computer-aided methods and discuss the required next steps to increase clinical impact.

cs.LG↗

arXiv2022

Ten years of image analysis and machine learning competitions in dementia

Machine learning methods exploiting multi-parametric biomarkers, especially based on neuroimaging, have huge potential to improve early diagnosis of dementia and to predict which individuals are at-risk of developing dementia. To benchmark algorithms in the field of machine learning and neuroimaging in dementia and assess their potential for use in clinical practice and clinical trials, seven grand challenges have been organized in the last decade. The seven grand challenges addressed questions related to screening, clinical status estimation, prediction and monitoring in (pre-clinical) dementia. There was little overlap in clinical questions, tasks and performance metrics. Whereas this aids providing insight on a broad range of questions, it also limits the validation of results across challenges. The validation process itself was mostly comparable between challenges, using similar methods for ensuring objective comparison, uncertainty estimation and statistical testing. In general, winning algorithms performed rigorous data preprocessing and combined a wide range of input features. Despite high state-of-the-art performances, most of the methods evaluated by the challenges are not clinically used. To increase impact, future challenges could pay more attention to statistical analysis of which factors relate to higher performance, to clinical questions beyond Alzheimer's disease, and to using testing data beyond the Alzheimer's Disease Neuroimaging Initiative. Grand challenges would be an ideal venue for assessing the generalizability of algorithm performance to unseen data of other cohorts. Key for increasing impact in this way are larger testing data sizes, which could be reached by sharing algorithms rather than data to exploit data that cannot be shared.

cs.LG↗

arXiv2021

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

q-bio.PE↗

arXiv2021

Time efficiency analysis for undersampled quantitative MRI acquisitions

To realize Quantitative MRI (QMRI) with clinically acceptable scan time, acceleration factors achieved by conventional parallel imaging techniques are often inadequate. Further acceleration is possible using model-based reconstruction. We propose a theoretical metric called TEUSQA: Time Efficiency for UnderSampled QMRI Acquisitions to inform sequence design and sample pattern optimisation. TEUSQA is designed for a particular class of reconstruction techniques that directly estimate tissue parameters, possibly using prior information to regularize the estimation. TEUSQA can be used to evaluate undersampling patterns for multi-contrast QMRI sequences targeting any tissue parameter. To verify the time efficiency predicted by TEUSQA, we performed Monte Carlo simulations and an accelerated parameter mapping with two sequences (Inversion prepared fast spin echo for T1 and T2 mapping and 3D GRASE for T2 and B0 inhomogeneity mapping). Using TEUSQA, we assessed several ways to generate undersampling patterns in silico, providing insight into the relation between sample distribution and time efficiency for different acceleration factors. The time efficiency predicted by TEUSQA was within 15 % of that observed in the Monte Carlo simulations and the prospective acquisition experiment. The assessment of undersampling patterns showed that a class of good patterns could be obtained by low-discrepancy sampling. We believe that TEUSQA offers a valuable instrument for developers of novel QMRI sequences pushing the boundaries of acceleration to achieve clinically feasible protocols. Finally, we applied a time-efficient undersampling pattern selected using TEUSQA for a 32-fold accelerated scan to map T1 and T2 mapping of a healthy volunteer.

eess.SP↗

arXiv2021

Automatic Segmentation of the Optic Nerve Head Region in Optical Coherence Tomography: A Methodological Review

The optic nerve head represents the intraocular section of the optic nerve (ONH), which is prone to damage by intraocular pressure. The advent of optical coherence tomography (OCT) has enabled the evaluation of novel optic nerve head parameters, namely the depth and curvature of the lamina cribrosa (LC). Together with the Bruch's membrane opening minimum-rim-width, these seem to be promising optic nerve head parameters for diagnosis and monitoring of retinal diseases such as glaucoma. Nonetheless, these optical coherence tomography derived biomarkers are mostly extracted through manual segmentation, which is time-consuming and prone to bias, thus limiting their usability in clinical practice. The automatic segmentation of optic nerve head in OCT scans could further improve the current clinical management of glaucoma and other diseases. This review summarizes the current state-of-the-art in automatic segmentation of the ONH in OCT. PubMed and Scopus were used to perform a systematic review. Additional works from other databases (IEEE, Google Scholar and ARVO IOVS) were also included, resulting in a total of 27 reviewed studies. For each algorithm, the methods, the size and type of dataset used for validation, and the respective results were carefully analyzed. The results show that deep learning-based algorithms provide the highest accuracy, sensitivity and specificity for segmenting the different structures of the ONH including the LC. However, a lack of consensus regarding the definition of segmented regions, extracted parameters and validation approaches has been observed, highlighting the importance and need of standardized methodologies for ONH segmentation.

eess.IV↗

arXiv2021

Signal-carrying speckle in Optical Coherence Tomography: a methodological review on biomedical applications

Significance: Speckle has historically been considered a source of noise in coherent light imaging. However, a number of works in optical coherence tomography (OCT) imaging have shown that speckle patterns may contain relevant information regarding sub-resolution and structural properties of the tissues from which it is originated. Aim: The objective of this work is to provide a comprehensive overview of the methods developed for retrieving speckle information in biomedical OCT applications. Approach: PubMed and Scopus databases were used to perform a systematic review on studies published until April 2021. From 134-screened studies, 37 were eligible for this review. Results: The studies have been clustered according to the nature of their analysis, namely static or dynamic, and all features were described and analysed. The results show that features retrieved from speckle can be used successfully in different applications, such as classification and segmentation. However, the results also show that speckle analysis is highly application-dependant, and the best approach varies between applications. Conclusions: Several of the reviewed analysis were only performed in a theoretical context or using phantoms, showing that signal-carrying speckle analysis in OCT imaging is still in its early stage, and further work is needed to validate its applicability and reproducibility in a clinical context.

physics.med-ph↗

arXiv2021

Cross-Cohort Generalizability of Deep and Conventional Machine Learning for MRI-based Diagnosis and Prediction of Alzheimer's Disease

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the ADNI (334 AD, 520 CN). Trained classifiers were subsequently applied to predict conversion to AD in ADNI MCI patients (231 converters, 628 non-converters) and in the independent Health-RI Parelsnoer data set. From this multi-center study representing a tertiary memory clinic population, we included 199 AD patients, 139 participants with subjective cognitive decline, 48 MCI patients converting to dementia, and 91 MCI patients who did not convert to dementia. AD-CN classification based on modulated GM maps resulted in a similar AUC for SVM (0.940) and CNN (0.933). Application to conversion prediction in MCI yielded significantly higher performance for SVM (0.756) than for CNN (0.742). In external validation, performance was slightly decreased. For AD-CN, it again gave similar AUCs for SVM (0.896) and CNN (0.876). For prediction in MCI, performances decreased for both SVM (0.665) and CNN (0.702). Both with SVM and CNN, classification based on modulated GM maps significantly outperformed classification based on minimally processed images. Deep and conventional classifiers performed equally well for AD classification and their performance decreased only slightly when applied to the external cohort. We expect that this work on external validation contributes towards translation of machine learning to clinical practice.

eess.IV↗

arXiv2021

Longitudinal diffusion MRI analysis using Segis-Net: a single-step deep-learning framework for simultaneous segmentation and registration

This work presents a single-step deep-learning framework for longitudinal image analysis, coined Segis-Net. To optimally exploit information available in longitudinal data, this method concurrently learns a multi-class segmentation and nonlinear registration. Segmentation and registration are modeled using a convolutional neural network and optimized simultaneously for their mutual benefit. An objective function that optimizes spatial correspondence for the segmented structures across time-points is proposed. We applied Segis-Net to the analysis of white matter tracts from N=8045 longitudinal brain MRI datasets of 3249 elderly individuals. Segis-Net approach showed a significant increase in registration accuracy, spatio-temporal segmentation consistency, and reproducibility comparing with two multistage pipelines. This also led to a significant reduction in the sample-size that would be required to achieve the same statistical power in analyzing tract-specific measures. Thus, we expect that Segis-Net can serve as a new reliable tool to support longitudinal imaging studies to investigate macro- and microstructural brain changes over time.

cs.CV↗

arXiv2021

Evaluating glioma growth predictions as a forward ranking problem

The problem of tumor growth prediction is challenging, but promising results have been achieved with both model-driven and statistical methods. In this work, we present a framework for the evaluation of growth predictions that focuses on the spatial infiltration patterns, and specifically evaluating a prediction of future growth. We propose to frame the problem as a ranking problem rather than a segmentation problem. Using the average precision as a metric, we can evaluate the results with segmentations while using the full spatiotemporal prediction. Furthermore, by separating the model goodness-of-fit from future predictive performance, we show that in some cases, a better fit of model parameters does not guarantee a better the predictive power.

eess.IV↗

arXiv2021

Learning unbiased group-wise registration (LUGR) and joint segmentation: evaluation on longitudinal diffusion MRI

Analysis of longitudinal changes in imaging studies often involves both segmentation of structures of interest and registration of multiple timeframes. The accuracy of such analysis could benefit from a tailored framework that jointly optimizes both tasks to fully exploit the information available in the longitudinal data. Most learning-based registration algorithms, including joint optimization approaches, currently suffer from bias due to selection of a fixed reference frame and only support pairwise transformations. We here propose an analytical framework based on an unbiased learning strategy for group-wise registration that simultaneously registers images to the mean space of a group to obtain consistent segmentations. We evaluate the proposed method on longitudinal analysis of a white matter tract in a brain MRI dataset with 2-3 time-points for 3249 individuals, i.e., 8045 images in total. The reproducibility of the method is evaluated on test-retest data from 97 individuals. The results confirm that the implicit reference image is an average of the input image. In addition, the proposed framework leads to consistent segmentations and significantly lower processing bias than that of a pair-wise fixed-reference approach. This processing bias is even smaller than those obtained when translating segmentations by only one voxel, which can be attributed to subtle numerical instabilities and interpolation. Therefore, we postulate that the proposed mean-space learning strategy could be widely applied to learning-based registration tasks. In addition, this group-wise framework introduces a novel way for learning-based longitudinal studies by direct construction of an unbiased within-subject template and allowing reliable and efficient analysis of spatio-temporal imaging biomarkers.

cs.CV↗

arXiv2020

Differential diagnosis and molecular stratification of gastrointestinal stromal tumors on CT images using a radiomics approach

Distinguishing gastrointestinal stromal tumors (GISTs) from other intra-abdominal tumors and GISTs molecular analysis is necessary for treatment planning, but challenging due to its rarity. The aim of this study was to evaluate radiomics for distinguishing GISTs from other intra-abdominal tumors, and in GISTs, predict the c-KIT, PDGFRA,BRAF mutational status and mitotic index (MI). All 247 included patients (125 GISTS, 122 non-GISTs) underwent a contrast-enhanced venous phase CT. The GIST vs. non-GIST radiomics model, including imaging, age, sex and location, had a mean area under the curve (AUC) of 0.82. Three radiologists had an AUC of 0.69, 0.76, and 0.84, respectively. The radiomics model had an AUC of 0.52 for c-KIT, 0.56 for c-KIT exon 11, and 0.52 for the MI. Hence, our radiomics model was able to distinguish GIST from non-GISTS with a performance similar to three radiologists, but was not able to predict the c-KIT mutation or MI.

eess.IV↗

arXiv2020

WHO 2016 subtyping and automated segmentation of glioma using multi-task deep learning

Accurate characterization of glioma is crucial for clinical decision making. A delineation of the tumor is also desirable in the initial decision stages but is a time-consuming task. Leveraging the latest GPU capabilities, we developed a single multi-task convolutional neural network that uses the full 3D, structural, pre-operative MRI scans to can predict the IDH mutation status, the 1p/19q co-deletion status, and the grade of a tumor, while simultaneously segmenting the tumor. We trained our method using the largest, most diverse patient cohort to date containing 1508 glioma patients from 16 institutes. We tested our method on an independent dataset of 240 patients from 13 different institutes, and achieved an IDH-AUC of 0.90, 1p/19q-AUC of 0.85, grade-AUC of 0.81, and a mean whole tumor DICE score of 0.84. Thus, our method non-invasively predicts multiple, clinically relevant parameters and generalizes well to the broader clinical population.

eess.IV↗

arXiv2020

Analyzing the effect of APOE on Alzheimer's disease progression using an event-based model for stratified populations

Alzheimer's disease (AD) is the most common form of dementia and is phenotypically heterogeneous. APOE is a triallelic gene which correlates with phenotypic heterogeneity in AD. In this work, we determined the effect of APOE alleles on the disease progression timeline of AD using a discriminative event-based model (DEBM). Since DEBM is a data-driven model, stratification into smaller disease subgroups would lead to more inaccurate models as compared to fitting the model on the entire dataset. Hence our secondary aim is to propose and evaluate novel approaches in which we split the different steps of DEBM into group-aspecific and group-specific parts, where the entire dataset is used to train the group-aspecific parts and only the data from a specific group is used to train the group-specific parts of the DEBM. We performed simulation experiments to benchmark the accuracy of the proposed approaches and to select the optimal approach. Subsequently, the chosen approach was applied to the baseline data of 417 cognitively normal, 235 mild cognitively impaired who convert to AD within 3 years, and 342 AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to gain new insights into the effect of APOE carriership on the disease progression timeline of AD. The presented models could aid understanding of the disease, and in selecting homogeneous group of presymptomatic subjects at-risk of developing symptoms for clinical trials.

cs.LG↗