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PURPOSE: Without a clear definition of an optimal treatment plan, no optimization model can be perfect. Therefore, instead of automatically finding a single “optimal” plan, finding multiple, yet different near-optimal plans, can be an insightful approach to support radiation oncologists in finding the plan they are looking for. METHODS AND MATERIALS: BRIGHT is a flexible AI-based optimization method for brachytherapy treatment planning that has already been shown capable of finding high-quality plans that trade-off target volume coverage and healthy tissue sparing. We leverage the flexibility of BRIGHT to find plans with similar dose-volume criteria, yet different dose distributions. We further describe extensions that facilitate fast plan adaptation should planning aims need to be adjusted, and straightforwardly allow incorporating hospital-specific aims besides standard protocols. RESULTS: Results are obtained for prostate (n = 12) and cervix brachytherapy (n = 36). We demonstrate the possible differences in dose distribution for optimized plans with equal dose-volume criteria. We furthermore demonstrate that adding hospital-specific aims enables adhering to hospital-specific practice while still being able to automatically create cervix plans that more often satisfy the EMBRACE-II protocol than clinical practice. Finally, we illustrate the feasibility of fast plan adaptation. CONCLUSIONS: Methods such as BRIGHT enable new ways to construct high-quality treatment plans for brachytherapy while offering new insights by making explicit the options one has. In particular, it becomes possible to present to radiation oncologists a manageable set of alternative plans that, from an optimization perspective are equally good, yet differ in terms of coverage-sparing trade-offs and shape of the dose distribution.

The transformation model is an essential component of any deformable image registration approach. It provides a representation of physical deformations between images, thereby defining the range and realism of registrations that can be found. Two types of transformation models have emerged as popular choices: B-spline models and mesh models. Although both models have been investigated in detail, a direct comparison has not yet been made, since the models are optimized using very different optimization methods in practice. B-spline models are predominantly optimized using gradient-descent methods, while mesh models are typically optimized using finite-element method solvers or evolutionary algorithms. Multi-objective optimization methods, which aim to find a diverse set of high-quality trade-off registrations, are increasingly acknowledged to be important in deformable image registration. Since these methods search for a diverse set of registrations, they can provide a more complete picture of the capabilities of different transformation models, making them suitable for a comparison of models. In this work, we conduct the first direct comparison between B-spline and mesh transformation models, by optimizing both models with the same state-of-the-art multi-objective optimization method, the Multi-Objective Real-Valued Gene-pool Optimal Mixing Evolutionary Algorithm (MO-RV-GOMEA). The combination with B-spline transformation models, moreover, is novel. We experimentally compare both models on two different registration problems that are both based on pelvic CT scans of cervical cancer patients, featuring large deformations. Our results, on three cervical cancer patients, indicate that the choice of transformation model can have a profound impact on the diversity and quality of achieved registration outcomes.

Volume measurement of a paraganglioma (a rare neuroendocrine tumor that typically forms along major blood vessels and nerve pathways in the head and neck region) is crucial for monitoring and modeling tumor growth in the long term. However, in clinical practice, using available tools to do these measurements is time-consuming and suffers from tumor-shape assumptions and observer-to-observer variation. Growth modeling could play a significant role in solving a decades-old dilemma (stemming from uncertainty regarding how the tumor will develop over time). By giving paraganglioma patients treatment, severe symptoms can be prevented. However, treating patients who do not actually need it, comes at the cost of unnecessary possible side effects and complications. Improved measurement techniques could enable growth model studies with a large amount of tumor volume data, possibly giving valuable insights into how these tumors develop over time. Therefore, we propose an automated tumor volume measurement method based on a deep learning segmentation model using no-new-UNnet (nnUNet). We assess the performance of the model based on visual inspection by a senior otorhinolaryngologist and several quantitative metrics by comparing model outputs with manual delineations, including a comparison with variation in manual delineation by multiple observers. Our findings indicate that the automatic method performs (at least) equal to manual delineation. Finally, using the created model, and a linking procedure that we propose to track the tumor over time, we show how additional volume measurements affect the fit of known growth functions.

Item does not contain fulltext, Antenatal assessment of congenital heart disease and associated anomalies by ultrasound has improved perinatal care. Fetal cardiovascular MRI and fetal brain MRI are rapidly evolving for fetal diagnostic testing of congenital heart disease. We give an overview on the use of fetal cardiovascular MRI and fetal brain MRI in congenital heart disease, focusing on the current applications and diagnostic yield of structural and functional imaging during pregnancy. Fetal cardiovascular MRI in congenital heart disease is a promising supplementary imaging method to echocardiography for the diagnosis of antenatal congenital heart disease in weeks 30-40 of pregnancy. Concomitant fetal brain MRI is superior to brain ultrasound to show the complex relationship between fetal haemodynamics in congenital heart disease and brain development.

In this work, we show that simultaneously training and mixing neural networks is a promising way to conduct Neural Architecture Search (NAS). For hyperparameter optimization, reusing the partially trained weights allows for efficient search, as was previously demonstrated by the Population Based Training (PBT) algorithm. We propose PBT-NAS, an adaptation of PBT to NAS where architectures are improved during training by replacing poorly-performing networks in a population with the result of mixing well-performing ones and inheriting the weights using the shrink-perturb technique. After PBT-NAS terminates, the created networks can be directly used without retraining. PBT-NAS is highly parallelizable and effective: on challenging tasks (image generation and reinforcement learning) PBT-NAS achieves superior performance compared to baselines (random search and mutation-based PBT)., Algorithmics

Validation of deformable image registration techniques is extremely important, but hard, especially when complex deformations or content mismatch are involved. These complex deformations and content mismatch, for example, occur after the placement of an applicator for brachytherapy for cervical cancer. Virtual phantoms could enable the creation of validation data sets with ground truth deformations that simulate the large deformations that occur between image acquisitions. However, the quality of the multi-organ Finite Element Method (FEM)-based simulations is dependent on the patient-specific external forces and mechanical properties assigned to the organs. A common approach to calibrate these simulation parameters is through optimization, finding the parameter settings that optimize the match between the outcome of the simulation and reality. When considering inherently simplified organ models, we hypothesize that the optimal deformations of one organ cannot be achieved with a single parameter setting without compromising the optimality of the deformation of the surrounding organs. This means that there will be a trade-off between the optimal deformations of adjacent organs, such as the vagina-uterus and bladder. This work therefore proposes and evaluates a multi-objective optimization approach where the trade-off between organ deformations can be assessed after optimization. We showcase what the extent of the trade-off looks like when bi-objectively optimizing the patient-specific mechanical properties and external forces of the vagina-uterus and bladder for FEM-based simulations.

Segmentation of regions of interest in images of patients, is a crucial step in many medical procedures. Deep neural networks have proven to be particularly adept at this task. However, a key question is what type of deep neural network to choose, and whether making a certain choice makes a difference. In this work, we will answer this question for the task of segmentation of the Organs At Risk (OARs) in radiation treatment of cervical cancer (i.e., bladder, bowel, rectum, sigmoid) in Magnetic Resonance Imaging (MRI) scans. We compare several state-of-the-art models belonging to different architecture categories, as well as a few new models that combine aspects of several state-of-the-art models, to see if the results one gets are markedly different. We visualize model predictions, create all possible ensembles of models by averaging their output probabilities, and calculate the Dice Coefficient between predictions of models, in order to understand the differences between them and the potential of possible combinations. The results show that small improvements in metrics can be achieved by advancing and merging architectures, but the predictions of the models are quite similar (most models achieve on average more than 0.8 Dice Coefficient when compared to the outputs of other models). However, the results from the ensemble experiments indicate that the best results are obtained when the best performing models from every category of the architectures are combined.

Population Based Training (PBT) is an efficient hyperparameter optimization algorithm. PBT is a single-objective algorithm, but many real-world hyperparameter optimization problems involve two or more conflicting objectives. In this work, we therefore introduce a multi-objective version of PBT, MO-PBT. Our experiments on diverse multi-objective hyperparameter optimization problems (Precision/Recall, Accuracy/Fairness, Accuracy/Adversarial Robustness) show that MO-PBT outperforms random search, single-objective PBT, and the state-of-the-art multi-objective hyperparameter optimization algorithm MO-ASHA.

Deep learning models benefit from training with a large dataset (labeled or unlabeled). Following this motivation, we present an approach to learn a deep learning model for the automatic segmentation of Organs at Risk (OARs) in cervical cancer radiation treatment from a large clinically available dataset of Computed Tomography (CT) scans containing data inhomogeneity, label noise, and missing annotations. We employ simple heuristics for automatic data cleaning to minimize data inhomogeneity and label noise. Further, we develop a semi-supervised learning approach utilizing a teacher-student setup, annotation imputation, and uncertainty-guided training to learn in presence of missing annotations. Our experimental results show that learning from a large dataset with our approach yields a significant improvement in the test performance despite missing annotations in the data. Further, the contours generated from the segmentation masks predicted by our model are found to be equally clinically acceptable as manually generated contours.

In this work, we show that simultaneously training and mixing neural networks is a promising way to conduct Neural Architecture Search (NAS). For hyperparameter optimization, reusing the partially trained weights allows for efficient search, as was previously demonstrated by the Population Based Training (PBT) algorithm. We propose PBT-NAS, an adaptation of PBT to NAS where architectures are improved during training by replacing poorly-performing networks in a population with the result of mixing well-performing ones and inheriting the weights using the shrink-perturb technique. After PBT-NAS terminates, the created networks can be directly used without retraining. PBT-NAS is highly parallelizable and effective: on challenging tasks (image generation and reinforcement learning) PBT-NAS achieves superior performance compared to baselines (random search and mutation-based PBT).

Real-world problems are often multi-objective, with decision-makers unable to specify a priori which trade-off between the conflicting objectives is preferable. Intuitively, building machine learning solutions in such cases would entail providing multiple predictions that span and uniformly cover the Pareto front of all optimal trade-off solutions. We propose a novel approach for multi-objective training of neural networks to approximate the Pareto front during inference. In our approach, we train the neural networks multi-objectively using a dynamic loss function, wherein each network’s losses (corresponding to multiple objectives) are weighted by their hypervolume maximizing gradients. Experiments on different multi-objective problems show that our approach returns well-spread outputs across different trade-offs on the approximated Pareto front without requiring the trade-off vectors to be specified a priori. Further, results of comparisons with the state-of-the-art approaches highlight the added value of our proposed approach, especially in cases where the Pareto front is asymmetric., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Algorithmics

The aim of Symbolic Regression (SR) is to discover interpretable expressions that accurately describe data. The accuracy of an expression depends on both its structure and coefficients. To keep the structure simple enough to be interpretable, effective coefficient optimisation becomes key. Gradient-based optimisation is clearly effective at training neural networks in Deep Learning (DL), which can essentially be viewed as large, over-parameterised expressions: in this paper, we study how gradient-based optimisation techniques as often used in DL transfer to SR. In particular, we first assess what techniques work well across random SR expressions, independent of any specific SR algorithm. We find that mini-batching and gradient-clipping can be helpful (similar to DL), while second-order optimisers outperform first-order ones (different from DL). Next, we consider whether including gradient-based optimisation in Genetic Programming (GP), a classic SR algorithm, is beneficial. On five real-world datasets, in a generation-based comparison, we find that second-order optimisation outperforms coefficient mutation (or no optimisation). However, in time-based comparisons, performance gaps shrink substantially because the computational expensiveness of second-order optimisation causes GP to perform fewer generations. The interplay of computational costs between the optimisation of structure and coefficients is thus a critical aspect to consider., Algorithmics

In a parallel EA one can strictly adhere to the generational clock, and wait for all evaluations in a generation to be done. However, this idle time limits the throughput of the algorithm and wastes computational resources. Alternatively, an EA can be made asynchronous parallel. However, EAs using classic recombination and selection operators (GAs) are known to suffer from an evaluation time bias, which also influences the performance of the approach. Model-Based Evolutionary Algorithms (MBEAs) are more scalable than classic GAs by virtue of capturing the structure of a problem in a model. If this model is learned through linkage learning based on the population, the learned model may also capture biases. Thus, if an asynchronous parallel MBEA is also affected by an evaluation time bias, this could result in learned models to be less suited to solving the problem, reducing performance. Therefore, in this work, we study the impact and presence of evaluation time biases on MBEAs in an asynchronous parallelization setting, and compare this to the biases in GAs. We find that a modern MBEA, GOMEA, is unaffected by evaluation time biases, while the more classical MBEA, ECGA, is affected, much like GAs are., Algorithmics

Finding a realistic deformation that transforms one image into another, in case large deformations are required, is considered a key challenge in medical image analysis. Having a proper image registration approach to achieve this could unleash a number of applications requiring information to be transferred between images. Clinical adoption is currently hampered by many existing methods requiring extensive configuration effort before each use, or not being able to (realistically) capture large deformations. A recent multi-objective approach that uses the Multi-Objective Real-Valued Gene-pool Optimal Mixing Evolutionary Algorithm (MO-RV-GOMEA) and a dual-dynamic mesh transformation model has shown promise, exposing the trade-offs inherent to image registration problems and modeling large deformations in 2D. This work builds on this promise and introduces MOREA: the first evolutionary algorithm-based multi-objective approach to deformable registration of 3D images capable of tackling large deformations. MOREA includes a 3D biomechanical mesh model for physical plausibility and is fully GPU-accelerated. We compare MOREA to two state-of-the-art approaches on abdominal CT scans of 4 cervical cancer patients, with the latter two approaches configured for the best results per patient. Without requiring per-patient configuration, MOREA significantly outperforms these approaches on 3 of the 4 patients that represent the most difficult cases.

Purpose: Deformable image registration (DIR) can benefit from additional guidance using corresponding landmarks in the images. However, the benefits thereof are largely understudied, especially due to the lack of automatic landmark detection methods for three-dimensional (3D) medical images. Approach: We present a deep convolutional neural network (DCNN), called DCNN-Match, that learns to predict landmark correspondences in 3D images in a self-supervised manner. We trained DCNN-Match on pairs of computed tomography (CT) scans containing simulated deformations. We explored five variants of DCNN-Match that use different loss functions and assessed their effect on the spatial density of predicted landmarks and the associated matching errors. We also tested DCNN-Match variants in combination with the open-source registration software Elastix to assess the impact of predicted landmarks in providing additional guidance to DIR. Results: We tested our approach on lower abdominal CT scans from cervical cancer patients: 121 pairs containing simulated deformations and 11 pairs demonstrating clinical deformations. The results showed significant improvement in DIR performance when landmark correspondences predicted by DCNN-Match were used in the case of simulated (p = 0e0) as well as clinical deformations (p = 0.030). We also observed that the spatial density of the automatic landmarks with respect to the underlying deformation affect the extent of improvement in DIR. Finally, DCNN-Match was found to generalize to magnetic resonance imaging scans without requiring retraining, indicating easy applicability to other datasets. Conclusions: DCNN-match learns to predict landmark correspondences in 3D medical images in a self-supervised manner, which can improve DIR performance., ense., Algorithmics

Purpose: This prospective study evaluates our first clinical experiences with the novel ‘‘BRachytherapy via artificial Intelligent GOMEA-Heuristic based Treatment planning'' (BRIGHT) applied to high-dose-rate prostate brachytherapy. MethodS AND MATERIALs: Between March 2020 and October 2021, 14 prostate cancer patients were treated in our center with a 15Gy HDR-brachytherapy boost. BRIGHT was used for bi-objective treatment plan optimization and selection of the most desirable plans from a coverage-sparing trade-off curve. Selected BRIGHT plans were imported into the commercial treatment planning system Oncentra Brachy. In Oncentra Brachy a dose distribution comparison was performed for clinical plan choice, followed by manual fine-tuning of the preferred BRIGHT plan when deemed necessary. The reasons for plan selection, clinical plan choice, and fine-tuning, as well as process speed were monitored. For each patient, the dose-volume parameters of the (fine-tuned) clinical plan were evaluated. Results: In all patients, BRIGHT provided solutions satisfying all protocol values for coverage and sparing. In four patients not all dose-volume criteria of the clinical plan were satisfied after manual fine-tuning. Detailed information on tumour coverage, dose-distribution, dwell time pattern, and insight provided by the patient-specific trade-off curve, were used for clinical plan choice. Median time spent on treatment planning was 42 min, consisting of 16 min plan optimization and selection, and 26 min undesirable process steps. ConclusionS: BRIGHT is implemented in our clinic and provides automated prostate high-dose-rate brachytherapy planning with trade-off based plan selection. Based on our experience, additional optimization aims need to be implemented to further improve direct clinical applicability of treatment plans and process efficiency.

Deep learning models benefit from training with a large dataset (labeled or unlabeled). Following this motivation, we present an approach to learn a deep learning model for the automatic segmentation of Organs at Risk (OARs) in cervical cancer radiation treatment from a large clinically available dataset of Computed Tomography (CT) scans containing data inhomogeneity, label noise, and missing annotations. We employ simple heuristics for automatic data cleaning to minimize data inhomogeneity and label noise. Further, we develop a semi-supervised learning approach utilizing a teacher-student setup, annotation imputation, and uncertainty-guided training to learn in presence of missing annotations. Our experimental results show that learning from a large dataset with our approach yields a significant improvement in the test performance despite missing annotations in the data. Further, the contours generated from the segmentation masks predicted by our model are found to be equally clinically acceptable as manually generated contours.

To achieve excellent performance with modern neural networks, having the right network architecture is important. Neural Architecture Search (NAS) concerns the automatic discovery of task-specific network architectures. Modern NAS approaches leverage super-networks whose subnetworks encode candidate neural network architectures. These subnetworks can be trained simultaneously, removing the need to train each network from scratch, thereby increasing the efficiency of NAS. A recent method called Neural Architecture Transfer (NAT) further improves the efficiency of NAS for computer vision tasks by using a multi-objective evolutionary algorithm to find high-quality subnetworks of a supernetwork pretrained on ImageNet. Building upon NAT, we introduce ENCAS - - Evolutionary Neural Cascade Search. ENCAS can be used to search over multiple pretrained supernetworks to achieve a trade-off front of cascades of different neural network architectures, maximizing accuracy while minimizing FLOPs count. We test ENCAS on common computer vision benchmarks (CIFAR-10, CIFAR-100, ImageNet) and achieve Pareto dominance over previous state-of-the-art NAS models up to 1.5 GFLOPs. Additionally, applying ENCAS to a pool of 518 publicly available ImageNet classifiers leads to Pareto dominance in all computation regimes and to increasing the maximum accuracy from 88.6% to 89.0%, accompanied by an 18% decrease in computation effort from 362 to 296 GFLOPs., Algorithmics

Genetic programming (GP) is one of the best approaches today to discover symbolic regression models. To find models that trade off accuracy and complexity, the non-dominated sorting genetic algorithm II (NSGA-II) is widely used. Unfortunately, it has been shown that NSGA-II can be inefficient: in early generations, low-complexity models over-replicate and take over most of the population. Consequently, studies have proposed different approaches to promote diversity. Here, we study the root of this problem, in order to design a superior approach. We find that the over-replication of low complexity-models is due to a lack of evolvability, i.e., the inability to produce offspring with improved accuracy. We therefore extend NSGA-II to track, over time, the evolvability of models of different levels of complexity. With this information, we limit how many models of each complexity level are allowed to survive the generation. We compare this new version of NSGA-II, evoNSGA-II, with the use of seven existing multi-objective GP approaches on ten widely-used data sets, and find that evoNSGA-II is equal or superior to using these approaches in almost all comparisons. Furthermore, our results confirm that evoNSGA-II behaves as intended: models that are more evolvable form the majority of the population. Code: https://github.com/dzhliu/evoNSGA-II, Algorithmics

Model-Based Evolutionary Algorithms (MBEAs) can be highly scalable by virtue of linkage (or variable interaction) learning. This requires, however, that the linkage model can capture the exploitable structure of a problem. Usually, a single type of linkage structure is attempted to be captured using models such as a linkage tree. However, in practice, problems may exhibit multiple linkage structures. This is for instance the case in multi-objective optimization when the objectives have different linkage structures. This cannot be modelled sufficiently well when using linkage models that aim at capturing a single type of linkage structure, deteriorating the advantages brought by MBEAs. Therefore, here, we introduce linkage kernels, whereby a linkage structure is learned for each solution over its local neighborhood. We implement linkage kernels into the MBEA known as GOMEA that was previously found to be highly scalable when solving various problems. We further introduce a novel benchmark function called Best-of-Traps (BoT) that has an adjustable degree of different linkage structures. On both BoT and a worst-case scenario-based variant of the well-known MaxCut problem, we experimentally find a vast performance improvement of linkage-kernel GOMEA over GOMEA with a single linkage tree as well as the MBEA known as DSMGA-II., Algorithmics

Deep learning algorithms have become the golden standard for segmentation of medical imaging data. In most works, the variability and heterogeneity of real clinical data is acknowledged to still be a problem. One way to automatically overcome this is to capture and exploit this variation explicitly. Here, we propose an approach that improves on our previous work in this area and explain how it potentially can improve clinical acceptance of (semi-)automatic segmentation methods. In contrast to a standard neural network that produces one segmentation, we propose to use a multi-path Unet network that produces multiple segmentation variants, presumably corresponding to the variations that reside in the dataset. Different paths of the network are trained on disjoint data subsets. Because a priori it may be unclear what variations exist in the data, the subsets should be automatically determined. This is achieved by searching for the best data partitioning with an evolutionary optimization algorithm. Because each network path can become more specialized when trained on a more homogeneous data subset, better segmentation quality can be achieved. In practical usage, various automatically produced segmentations can be presented to a medical expert, from which the preferred segmentation can be selected. In experiments with a real clinical dataset of CT scans with prostate segmentations, our approach provides an improvement of several percentage points in terms of Dice and surface Dice coefficients compared to when all network paths are trained on all training data. Noticeably, the largest improvement occurs in the upper part of the prostate that is known to be most prone to inter-observer segmentation variation.

Deep Neural Networks (DNNs) have the potential for making various clinical procedures more time-efficient by automating medical image segmentation. Due to their strong, in some cases human-level, performance, they have become the standard approach in this field. The design of the best possible medical image segmentation DNNs, however, is task-specific. Neural Architecture Search (NAS), i.e., the automation of neural network design, has been shown to have the capability to outperform manually designed networks for various tasks. However, the existing NAS methods for medical image segmentation have explored a quite limited range of types of DNN architectures that can be discovered. In this work, we propose a novel NAS search space for medical image segmentation networks. This search space combines the strength of a generalised encoder-decoder structure, well known from U-Net, with network blocks that have proven to have a strong performance in image classification tasks. The search is performed by looking for the best topology of multiple cells simultaneously with the configuration of each cell within, allowing for interactions between topology and cell-level attributes. From experiments on two publicly available datasets, we find that the networks discovered by our proposed NAS method have better performance than well-known handcrafted segmentation networks, and outperform networks found with other NAS approaches that perform only topology search, and topology-level search followed by cell-level search.

Reliably and physically accurately transferring information between images through deformable image registration with large anatomical differences is an open challenge in medical image analysis. Most existing methods have two key shortcomings: first, they require extensive up-front parameter tuning to each specific registration problem, and second, they have difficulty capturing large deformations and content mismatches between images. There have however been developments that have laid the foundation for potential solutions to both shortcomings. Towards the first shortcoming, a multi-objective optimization approach using the Real-Valued Gene-pool Optimal Mixing Evolutionary Algorithm (RV-GOMEA) has been shown to be capable of producing a diverse set of registrations for 2D images in one run of the algorithm, representing different trade-offs between conflicting objectives in the registration problem. This allows the user to select a registration afterwards and removes the need for up-front tuning. Towards the second shortcoming, a dual-dynamic grid transformation model has proven effective at capturing large differences in 2D images. These two developments have recently been accelerated through GPU parallelization, delivering large speed-ups. Based on this accelerated version, it is now possible to extend the approach to 3D images. Concordantly, this work introduces the first method for multi-objective 3D deformable image registration, using a 3D dual-dynamic grid transformation model based on simplex meshes while still supporting the incorporation of annotated guidance information and multi-resolution schemes. Our proof-of-concept prototype shows promising results on synthetic and clinical 3D registration problems, forming the foundation for a new, insightful method that can include bio-mechanical properties in the registration.

Even if a Multi-modal Multi-Objective Evolutionary Algorithm (MMOEA) is designed to find solutions well spread over all locally optimal approximation sets of a Multi-modal Multi-objective Optimization Problem (MMOP), there is a risk that the found set of solutions is not smoothly navigable because the solutions belong to various niches, reducing the insight for decision makers. To tackle this issue, a new MMOEAs is proposed: the Multi-Modal Bézier Evolutionary Algorithm (MM-BezEA), which produces approximation sets that cover individual niches and exhibit inherent decision-space smoothness as they are parameterized by Bézier curves. MM-BezEA combines the concepts behind the recently introduced BezEA and MO-HillVallEA to find all locally optimal approximation sets. When benchmarked against the MMOEAs MO_Ring_PSO_SCD and MO-HillVallEA on MMOPs with linear Pareto sets, MM-BezEA was found to perform best in terms of best hypervolume.

Purpose: Our purpose was to validate and compare the performance of 4 organ dose reconstruction approaches for historical radiation treatment planning based on 2-dimensional radiographs. Methods and Materials: We considered 10 patients with Wilms tumor with planning computed tomography images for whom we developed typical historic Wilms tumor radiation treatment plans, using anteroposterior and posteroanterior parallel-opposed 6 MV flank fields, normalized to 14.4 Gy. Two plans were created for each patient, with and without corner blocking. Regions of interest (lungs, heart, nipples, liver, spleen, contralateral kidney, and spinal cord) were delineated, and dose-volume metrics including organ mean and minimum dose (Dmean and Dmin) were computed as the reference baseline for comparison. Dosimetry for the 20 plans was then independently reconstructed using 4 different approaches. Three approaches involved surrogate anatomy, among which 2 used demographic-matching criteria for phantom selection/building, and 1 used machine learning. The fourth approach was also machine learning-based, but used no surrogate anatomies. Absolute differences in organ dose-volume metrics between the reconstructed and the reference values were calculated. Results: For Dmean and Dmin (average and minimum point dose) all 4 dose reconstruction approaches performed within 10% of the prescribed dose (≤1.4 Gy). The machine learning-based approaches showed a slight advantage for several of the considered regions of interest. For Dmax (maximum point dose), the absolute differences were much higher, that is, exceeding 14% (2 Gy), with the poorest agreement observed for near-beam and out-of-beam organs for all approaches. Conclusions: The studied approaches give comparable dose reconstruction results, and the choice of approach for cohort dosimetry for late effects studies should still be largely driven by the available resources (data, time, expertise, and funding).

Domination-based multiobjective (MO) evolutionary algorithms (EAs) are today arguably the most frequently used type of MOEA. These methods, however, stagnate when the majority of the population becomes nondominated, preventing further convergence to the Pareto set. Hypervolume-based MO optimization has shown promising results to overcome this. Direct use of the hypervolume, however, results in no selection pressure for dominated solutions. The recently introduced Sofomore framework overcomes this by solving multiple interleaved single-objective dynamic problems that iteratively improve a single approximation set, based on the uncrowded hypervolume improvement (UHVI). It thereby however loses many advantages of population-based MO optimization, such as handling multimodality. Here, we reformulate the UHVI as a quality measure for approximation sets, called the uncrowded hypervolume (UHV), which can be used to directly solve MO optimization problems with a single-objective optimizer. We use the state-of-the-art gene-pool optimal mixing evolutionary algorithm (GOMEA) that is capable of efficiently exploiting the intrinsically available grey-box properties of this problem. The resulting algorithm, UHV-GOMEA, is compared with Sofomore equipped with GOMEA, and the domination-based MO-GOMEA. In doing so, we investigate in which scenarios either domination-based or hypervolume-based methods are preferred. Finally, we construct a simple hybrid approach that combines MO-GOMEA with UHV-GOMEA and outperforms both.

Neural Architecture Search (NAS) has recently become a topic of great interest. However, there is a potentially impactful issue within NAS that remains largely unrecognized: noise. Due to stochastic factors in neural network initialization, training, and the chosen train/validation dataset split, the performance evaluation of a neural network architecture, which is often based on a single learning run, is also stochastic. This may have a particularly large impact if a dataset is small. We therefore propose to reduce this noise by evaluating architectures based on average performance over multiple network training runs using different random seeds and cross-validation. We perform experiments for a combinatorial optimization formulation of NAS in which we vary noise reduction levels. We use the same computational budget for each noise level in terms of network training runs, i.e., we allow less architecture evaluations when averaging over more training runs. Multiple search algorithms are considered, including evolutionary algorithms which generally perform well for NAS. We use two publicly available datasets from the medical image segmentation domain where datasets are often limited and variability among samples is often high. Our results show that reducing noise in architecture evaluations enables finding better architectures by all considered search algorithms.

Explainable artificial intelligence (XAI) is an important and rapidly expanding research topic. The goal of XAI is to gain trust in a machine learning (ML) model through clear insights into how the model arrives at its predictions. Genetic programming (GP) is often cited as being uniquely well-suited to contribute to XAI because of its capacity to learn (small) symbolic models that have the potential to be interpreted. Nevertheless, like many ML algorithms, GP typically results in a single best model. However, in practice, the best model in terms of training error may well not be the most suitable one as judged by a domain expert for various reasons, including overfitting, multiple different models existing that have similar accuracy and unwanted errors on particular data points due to typical accuracy measures like mean squared error. Hence, to increase chances that domain experts deem a resulting model plausible, it becomes important to be able to explicitly search for multiple, diverse, high-quality models that trade-off different meanings of accuracy. In this paper, we achieve exactly this with a novel multi-modal multi-tree multi-objective GP approach that extends a modern model-based GP algorithm known as GP-GOMEA that is already effective at searching for small expressions.

Model-Based Evolutionary Algorithms (MBEAs) can be highly scalable by virtue of linkage (or variable interaction) learning. This requires, however, that the linkage model can capture the exploitable structure of a problem. Usually, a single type of linkage structure is attempted to be captured using models such as a linkage tree. However, in practice, problems may exhibit multiple linkage structures. This is for instance the case in multi-objective optimization when the objectives have different linkage structures. This cannot be modelled sufficiently well when using linkage models that aim at capturing a single type of linkage structure, deteriorating the advantages brought by MBEAs. Therefore, here, we introduce linkage kernels, whereby a linkage structure is learned for each solution over its local neighborhood. We implement linkage kernels into the MBEA known as GOMEA that was previously found to be highly scalable when solving various problems. We further introduce a novel benchmark function called Best-of-Traps (BoT) that has an adjustable degree of different linkage structures. On both BoT and a worst-case scenario-based variant of the well-known MaxCut problem, we experimentally find a vast performance improvement of linkage-kernel GOMEA over GOMEA with a single linkage tree as well as the MBEA known as DSMGA-II.

Dimensionality reduction (DR) is an important technique for data exploration and knowledge discovery. However, most of the main DR methods are either linear (e.g., PCA), do not provide an explicit mapping between the original data and its lower-dimensional representation (e.g., MDS, t-SNE, isomap), or produce mappings that cannot be easily interpreted (e.g., kernel PCA, neural-based autoencoder). Recently genetic programming (GP) has been used to evolve interpretable DR mappings in the form of symbolic expressions. There exists a number of ways in which GP can be used to this end and no study exists that performs a comparison. In this paper, we fill this gap by comparing existing GP methods as well as devising new ones. We evaluate our methods on several benchmark datasets based on predictive accuracy and on how well the original features can be reconstructed using the lower-dimensional representation only. Finally we qualitatively assess the resulting expressions and their complexity. We find that various GP methods can be competitive with state-of-the-art DR algorithms and that they have the potential to produce interpretable DR mappings.

The Multi-Objective Real-Valued Gene-pool Optimal Mixing Evolutionary Algorithm (MO-RV-GOMEA) has been proven effective and eficient in solving real-world problems. A prime example is optimizing treatment plans for prostate cancer brachytherapy, an internal form of radiation treatment, for which equally important clinical aims from a base protocol are grouped into two objectives and bi-objectively optimized. This use of MO-RV-GOMEA was recently successfully introduced into clinical practice. Brachytherapy can also play an important role in treating cervical cancer. However, using the same approach to optimize treatment plans often does not immediately lead to clinically desirable results. Concordantly, medical experts indicate that they use additional aims beyond the cervix base protocol. Moreover, these aims have different priorities and can be patient-specifically adjusted. For this reason, we propose a novel adaptive objective configuration method to use with MO-RV-GOMEA so that we can accommodate additional aims of this nature. Based on results using only the base protocol, in consultation with medical experts, we configured key additional aims. We show how, for 10 patient cases, the new approach achieves the intended result, properly taking into account the additional aims. Consequently, plans resulting from the new approach are preferred by medical specialists in 8/10 cases.

Genetic Programming (GP) can make an important contribution to explainable artificial intelligence because it can create symbolic expressions as machine learning models. Nevertheless, to be explainable, the expressions must not become too large. This may, however, limit their potential to be accurate. The re-use of subexpressions has the unique potential to mitigate this issue. The Genetic Programming Gene-pool Optimal Mixing Evolutionary Algorithm (GP-GOMEA) is a recent model-based GP approach that has been found particularly capable of evolving small expressions. However, its tree representation offers no explicit mechanisms to re-use subexpressions. By contrast, the graph representation in Cartesian GP (CGP) is natively capable of re-use. For this reason, we introduce CGP-GOMEA, a variant of GP-GOMEA that uses graphs instead of trees. We experimentally compare various configurations of CGP-GOMEA with GP-GOMEA and find that CGP-GOMEA performs on par with GP-GOMEA on three common datasets. Moreover, CGP-GOMEA is found to produce models that re-use subexpressions more often than GP-GOMEA uses duplicate subexpressions. This indicates that CGP-GOMEA has unique added potential, allowing to find even smaller expressions than GP-GOMEA with similar accuracy., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Algorithmics