Daniele Loiacono

Pier Luca Lanzi, Daniele Loiacono

Large language models (LLMs) have taken the scientific world by storm, changing the landscape of natural language processing and human-computer interaction. These powerful tools can answer complex questions and, surprisingly, perform challenging creative tasks (e.g., generate code and applications to solve problems, write stories, pieces of music, etc.). In this paper, we present a collaborative game design framework that combines interactive evolution and large language models to simulate the typical human design process. We use the former to exploit users' feedback for selecting the most promising ideas and large language models for a very complex creative task - the recombination and variation of ideas. In our framework, the process starts with a brief and a set of candidate designs, either generated using a language model or proposed by the users. Next, users collaborate on the design process by providing feedback to an interactive genetic algorithm that selects, recombines, and mutates the most promising designs. We evaluated our framework on three game design tasks with human designers who collaborated remotely.

Simone de Donato, Pier Luca Lanzi, Daniele Loiacono

We investigate the application of MAP-Elites (a well-known quality diversity algorithm) to design levels for First-Person Shooter (FPS) games. We consider two well-known map representations (All-Black and Grid-Graph) and introduce two novel representations (Point-Line and Spatial-Layout) that improve the characterization of FPS maps. We define a series of metrics to describe maps' topological properties (which solely depend on maps' layout), and emergent properties (which must be evaluated through actual gameplay). We perform an in-depth analysis to identify the most suitable features to guide MAP-Elites illumination process. We apply MAP-Elites with Sliding Boundaries (MESB) to evolve populations of FPS maps. Our results show that the new representations can generate maps with higher diversity and quality than the representations previously used for evolving FPS maps.

Leonardo Crespi, Samuele Camnasio, Damiano Dei et al.

In many clinical settings, the use of both Computed Tomography (CT) and Magnetic Resonance (MRI) is necessary to pursue a thorough understanding of the patient's anatomy and to plan a suitable therapeutical strategy; this is often the case in MRI-based radiotherapy, where CT is always necessary to prepare the dose delivery, as it provides the essential information about the radiation absorption properties of the tissues. Sometimes, MRI is preferred to contour the target volumes. However, this approach is often not the most efficient, as it is more expensive, time-consuming and, most importantly, stressful for the patients. To overcome this issue, in this work, we analyse the capabilities of different configurations of Deep Learning models to generate synthetic CT scans from MRI, leveraging the power of Generative Adversarial Networks (GANs) and, in particular, the CycleGAN architecture, capable of working in an unsupervised manner and without paired images, which were not available. Several CycleGAN models were trained unsupervised to generate CT scans from different MRI modalities with and without contrast agents. To overcome the problem of not having a ground truth, distribution-based metrics were used to assess the model's performance quantitatively, together with a qualitative evaluation where physicians were asked to differentiate between real and synthetic images to understand how realistic the generated images were. The results show how, depending on the input modalities, the models can have very different performances; however, models with the best quantitative results, according to the distribution-based metrics used, can generate very difficult images to distinguish from the real ones, even for physicians, demonstrating the approach's potential.

Ricardo Coimbra Brioso, Damiano Dei, Nicola Lambri et al.

Radiotherapy requires precise segmentation of organs at risk (OARs) and of the Clinical Target Volume (CTV) to maximize treatment efficacy and minimize toxicity. While deep learning (DL) has significantly advanced automatic contouring, complex targets like CTVs remain challenging. This study explores the use of simpler, well-segmented structures (e.g., OARs) as Anatomical Prior (AP) information to improve CTV segmentation. We investigate gender bias in segmentation models and the mitigation effect of the prior information. Findings indicate that incorporating prior knowledge with the discussed strategies enhances segmentation quality in female patients and reduces gender bias, particularly in the abdomen region. This research provides a comparative analysis of new encoding strategies and highlights the potential of using AP to achieve fairer segmentation outcomes.

Ricardo Coimbra Brioso, Damiano Dei, Ciro Franzese et al.

Radiotherapy (RT) is a key component in the treatment of various cancers, including Acute Lymphocytic Leukemia (ALL) and Acute Myelogenous Leukemia (AML). Precise delineation of organs at risk (OARs) and target areas is essential for effective treatment planning. Intensity Modulated Radiotherapy (IMRT) techniques, such as Total Marrow Irradiation (TMI) and Total Marrow and Lymph node Irradiation (TMLI), provide more precise radiation delivery compared to Total Body Irradiation (TBI). However, these techniques require time-consuming manual segmentation of structures in Computerized Tomography (CT) scans by the Radiation Oncologist (RO). In this paper, we present a deep learning-based auto-contouring method for segmenting Planning Target Volume (PTV) for TMLI treatment using the U-Net architecture. We trained and compared two segmentation models with two different loss functions on a dataset of 100 patients treated with TMLI at the Humanitas Research Hospital between 2011 and 2021. Despite challenges in lymph node areas, the best model achieved an average Dice score of 0.816 for PTV segmentation. Our findings are a preliminary but significant step towards developing a segmentation model that has the potential to save radiation oncologists a considerable amount of time. This could allow for the treatment of more patients, resulting in improved clinical practice efficiency and more reproducible contours.

Leonardo Crespi, Paolo Roncaglioni, Damiano Dei et al.

In the medical images field, semantic segmentation is one of the most important, yet difficult and time-consuming tasks to be performed by physicians. Thanks to the recent advancement in the Deep Learning models regarding Computer Vision, the promise to automate this kind of task is getting more and more realistic. However, many problems are still to be solved, like the scarce availability of data and the difficulty to extend the efficiency of highly specialised models to general scenarios. Organs at risk segmentation for radiotherapy treatment planning falls in this category, as the limited data available negatively affects the possibility to develop general-purpose models; in this work, we focus on the possibility to solve this problem by presenting three types of ensembles of single-organ models able to produce multi-organ masks exploiting the different specialisations of their components. The results obtained are promising and prove that this is a possible solution to finding efficient multi-organ segmentation methods.

Leonardo Crespi, Mattia Portanti, Daniele Loiacono

Organ at Risk (OAR) segmentation from CT scans is a key component of the radiotherapy treatment workflow. In recent years, deep learning techniques have shown remarkable potential in automating this process. In this paper, we investigate the performance of Generative Adversarial Networks (GANs) compared to supervised learning approaches for segmenting OARs from CT images. We propose three GAN-based models with identical generator architectures but different discriminator networks. These models are compared with well-established CNN models, such as SE-ResUnet and DeepLabV3, using the StructSeg dataset, which consists of 50 annotated CT scans containing contours of six OARs. Our work aims to provide insight into the advantages and disadvantages of adversarial training in the context of OAR segmentation. The results are very promising and show that the proposed GAN-based approaches are similar or superior to their CNN-based counterparts, particularly when segmenting more challenging target organs.

Ricardo Coimbra Brioso, Lorenzo Mondo, Damiano Dei et al.

Accurate delineation of the Clinical Target Volume (CTV) is essential for radiotherapy planning, yet remains time-consuming and difficult to assess, especially for complex treatments such as Total Marrow and Lymph Node Irradiation (TMLI). While deep learning-based auto-segmentation can reduce workload, safe clinical deployment requires reliable cues indicating where models may be wrong. In this work, we propose a budget-aware uncertainty-driven quality assurance (QA) framework built on nnU-Net, combining uncertainty quantification and post-hoc calibration to produce voxel-wise uncertainty maps (based on predictive entropy) that can guide targeted manual review. We compare temperature scaling (TS), deep ensembles (DE), checkpoint ensembles (CE), and test-time augmentation (TTA), evaluated both individually and in combination on TMLI as a representative use case. Reliability is assessed through ROI-masked calibration metrics and uncertainty--error alignment under realistic revision constraints, summarized as AUC over the top 0-5% most uncertain voxels. Across configurations, segmentation accuracy remains stable, whereas TS substantially improves calibration. Uncertainty-error alignment improves most with calibrated checkpoint-based inference, leading to uncertainty maps that highlight more consistently regions requiring manual edits. Overall, integrating calibration with efficient ensembling seems a promising strategy to implement a budget-aware QA workflow for radiotherapy segmentation.

Ricardo Coimbra Brioso, Giulio Sichili, Damiano Dei et al.

Perturbation-based explainability methods such as KernelSHAP provide model-agnostic attributions but are typically impractical for patch-based 3D medical image segmentation due to the large number of coalition evaluations and the high cost of sliding-window inference. We present an efficient KernelSHAP framework for volumetric CT segmentation that restricts computation to a user-defined region of interest and its receptive-field support, and accelerates inference via patch logit caching, reusing baseline predictions for unaffected patches while preserving nnU-Net's fusion scheme. To enable clinically meaningful attributions, we compare three automatically generated feature abstractions within the receptive-field crop: whole-organ units, regular FCC supervoxels, and hybrid organ-aware supervoxels, and we study multiple aggregation/value functions targeting stabilizing evidence (TP/Dice/Soft Dice) or false-positive behavior. Experiments on whole-body CT segmentations show that caching substantially reduces redundant computation (with computational savings ranging from 15% to 30%) and that faithfulness and interpretability exhibit clear trade-offs: regular supervoxels often maximize perturbation-based metrics but lack anatomical alignment, whereas organ-aware units yield more clinically interpretable explanations and are particularly effective for highlighting false-positive drivers under normalized metrics.

Viktor Rogowski, Maarten L. Terpstra, Niklas Wahl et al.

Radiation therapy (RT) requires precise dose delivery over multiple fractions, with CT fundamental for treatment planning due to its electron density information. Repeated CT acquisitions impose radiation exposure and logistical burdens, MRI lacks electron density, and cone-beam CT (CBCT) requires correction for dose calculation. Synthetic CT (sCT) generation addresses these by converting MRI or CBCT into CT-equivalent images with accurate Hounsfield Unit (HU) values, enabling MRI-only RT and CBCT-based adaptive workflows. Building on SynthRAD2023, SynthRAD2025 benchmarked sCT methods on 2,362 patients from five European centers across head and neck, thorax, and abdomen. Two tasks: MRI-to-CT (890 cases) and CBCT-to-CT (1,472 cases), evaluated via image similarity (MAE, PSNR, MS-SSIM), segmentation (Dice, HD95), and dosimetric metrics from photon and proton plans. With 803 participants and 12/13 valid submissions, Task 1 top performance reached MAE $64.8\pm21.3$ HU, PSNR $\sim$30 dB, MS-SSIM $\sim$0.936, Dice 0.79, photon $γ_{2\%/2\text{mm}}>98\%$, proton $γ\approx85\%$. Task 2 improved: MAE $48.3\pm13.4$ HU, PSNR 32.6 dB, MS-SSIM 0.968, Dice 0.86, photon $γ>99\%$, proton $γ\approx89\%$. Strong image--segmentation correlations ($ρ=0.78$--$0.79$) but moderate dose correlations confirmed image quality is insufficient as a dosimetric surrogate. Head-and-neck cases were most consistent; thoracic and abdominal cases showed greater variability. Residual errors at tissue interfaces propagate along beam paths, affecting proton dose more than photon. SynthRAD2025 demonstrates that deep learning yields clinically relevant sCTs, especially for CBCT-to-CT, while identifying persistent MRI-to-CT challenges and underscoring dose-based evaluation as essential for clinical validation.

Mahshid Shiri, Chandra Bortolotto, Alessandro Bruno et al.

Generative Adversarial Networks (GANs) are increasingly used to generate synthetic medical images, addressing the critical shortage of annotated data for training Artificial Intelligence systems. This study introduces CRF-GAN, a novel memory-efficient GAN architecture that enhances structural consistency in 3D medical image synthesis. Integrating Conditional Random Fields within a two-step generation process allows CRF-GAN improving spatial coherence while maintaining high-resolution image quality. The model's performance is evaluated against the state-of-the-art hierarchical (HA)-GAN model. Materials and Methods: We evaluate the performance of CRF-GAN against the HA-GAN model. The comparison between the two models was made through a quantitative evaluation, using FID and MMD metrics, and a qualitative evaluation, through a two-alternative forced choice (2AFC) test completed by a pool of 12 resident radiologists, to assess the realism of the generated images. Results: CRF-GAN outperformed HA-GAN with lower FID and MMD scores, indicating better image fidelity. The 2AFC test showed a significant preference for images generated by CRF-Gan over those generated by HA-GAN. Additionally, CRF-GAN demonstrated 9.34% lower memory usage and achieved up to 14.6% faster training speeds, offering substantial computational savings. Discussion: CRF-GAN model successfully generates high-resolution 3D medical images with non-inferior quality to conventional models, while being more memory-efficient and faster. The key objective was not only to lower the computational cost but also to reallocate the freed-up resources towards the creation of higher-resolution 3D imaging, which is still a critical factor limiting their direct clinical applicability. Moreover, unlike many previous studies, we combined qualitative and quantitative assessments to obtain a more holistic feedback on the model's performance.

Mahshid Shiri, Alessandro Bruno, Daniele Loiacono

Generative Adversarial Networks (GANs) have many potential medical imaging applications. Due to the limited memory of Graphical Processing Units (GPUs), most current 3D GAN models are trained on low-resolution medical images, these models cannot scale to high-resolution or are susceptible to patchy artifacts. In this work, we propose an end-to-end novel GAN architecture that uses Conditional Random field (CRF) to model dependencies so that it can generate consistent 3D medical Images without exploiting memory. To achieve this purpose, the generator is divided into two parts during training, the first part produces an intermediate representation and CRF is applied to this intermediate representation to capture correlations. The second part of the generator produces a random sub-volume of image using a subset of the intermediate representation. This structure has two advantages: first, the correlations are modeled by using the features that the generator is trying to optimize. Second, the generator can generate full high-resolution images during inference. Experiments on Lung CTs and Brain MRIs show that our architecture outperforms state-of-the-art while it has lower memory usage and less complexity.

Ricardo Coimbra Brioso, Leonardo Crespi, Andrea Seghetto et al.

A key step in Adaptive Radiation Therapy (ART) workflows is the evaluation of the patient's anatomy at treatment time to ensure the accuracy of the delivery. To this end, Cone Beam Computerized Tomography (CBCT) is widely used being cost-effective and easy to integrate into the treatment process. Nonetheless, CBCT images have lower resolution and more artifacts than CT scans, making them less reliable for precise treatment validation. Moreover, in complex treatments such as Total Marrow and Lymph Node Irradiation (TMLI), where full-body visualization of the patient is critical for accurate dose delivery, the CBCT images are often discontinuous, leaving gaps that could contain relevant anatomical information. To address these limitations, we propose ARTInp (Adaptive Radiation Therapy Inpainting), a novel deep-learning framework combining image inpainting and CBCT-to-CT translation. ARTInp employs a dual-network approach: a completion network that fills anatomical gaps in CBCT volumes and a custom Generative Adversarial Network (GAN) to generate high-quality synthetic CT (sCT) images. We trained ARTInp on a dataset of paired CBCT and CT images from the SynthRad 2023 challenge, and the performance achieved on a test set of 18 patients demonstrates its potential for enhancing CBCT-based workflows in radiotherapy.

Ricardo Coimbra Brioso, Damiano Dei, Nicola Lambri et al.

In order to optimize the radiotherapy delivery for cancer treatment, especially when dealing with complex treatments such as Total Marrow and Lymph Node Irradiation (TMLI), the accurate contouring of the Planning Target Volume (PTV) is crucial. Unfortunately, relying on manual contouring for such treatments is time-consuming and prone to errors. In this paper, we investigate the application of Deep Learning (DL) to automate the segmentation of the PTV in TMLI treatment, building upon previous work that introduced a solution to this problem based on a 2D U-Net model. We extend the previous research (i) by employing the nnU-Net framework to develop both 2D and 3D U-Net models and (ii) by evaluating the trained models on the PTV with the exclusion of bones, which consist mainly of lymp-nodes and represent the most challenging region of the target volume to segment. Our result show that the introduction of nnU-NET framework led to statistically significant improvement in the segmentation performance. In addition, the analysis on the PTV after the exclusion of bones showed that the models are quite robust also on the most challenging areas of the target volume. Overall, our study is a significant step forward in the application of DL in a complex radiotherapy treatment such as TMLI, offering a viable and scalable solution to increase the number of patients who can benefit from this treatment.

Elio Sasso, Daniele Loiacono, Pier Luca Lanzi

We present a tool for exploring the design space of shaders using an interactive evolutionary algorithm integrated with the Unity editor, a well-known commercial tool for video game development. Our framework leverages the underlying graph-based representation of recent shader editors and interactive evolution to allow designers to explore several visual options starting from an existing shader. Our framework encodes the graph representation of a current shader as a chromosome used to seed the evolution of a shader population. It applies graph-based recombination and mutation with a set of heuristics to create feasible shaders. The framework is an extension of the Unity editor; thus, designers with little knowledge of evolutionary computation (and shader programming) can interact with the underlying evolutionary engine using the same visual interface used for working on game scenes.

Edoardo Giacomello, Michele Cataldo, Daniele Loiacono et al.

Deep Learning has established in the latest years as a successful approach to address a great variety of tasks. Healthcare is one of the most promising field of application for Deep Learning approaches since it would allow to help clinicians to analyze patient data and perform diagnoses. However, despite the vast amount of data collected every year in hospitals and other clinical institutes, privacy regulations on sensitive data - such as those related to health - pose a serious challenge to the application of these methods. In this work, we focus on strategies to cope with privacy issues when a consortium of healthcare institutions needs to train machine learning models for identifying a particular disease, comparing the performances of two recent distributed learning approaches - Federated Learning and Split Learning - on the task of Automated Chest X-Ray Diagnosis. In particular, in our analysis we investigated the impact of different data distributions in client data and the possible policies on the frequency of data exchange between the institutions.

Leonardo Crespi, Daniele Loiacono, Arturo Chiti

Chest X-Ray (CXR) is one of the most common diagnostic techniques used in everyday clinical practice all around the world. We hereby present a work which intends to investigate and analyse the use of Deep Learning (DL) techniques to extract information from such images and allow to classify them, trying to keep our methodology as general as possible and possibly also usable in a real world scenario without much effort, in the future. To move in this direction, we trained several beta-Variational Autoencoder (beta-VAE) models on the CheXpert dataset, one of the largest publicly available collection of labeled CXR images; from these models, latent features have been extracted and used to train other Machine Learning models, able to classify the original images from the features extracted by the beta-VAE. Lastly, tree-based models have been combined together in ensemblings to improve the results without the necessity of further training or models engineering. Expecting some drop in pure performance with the respect to state of the art classification specific models, we obtained encouraging results, which show the viability of our approach and the usability of the high level features extracted by the autoencoders for classification tasks.

Edoardo Giacomello, Pier Luca Lanzi, Daniele Loiacono et al.

Chest X-ray (CXR) is perhaps the most frequently-performed radiological investigation globally. In this work, we present and study several machine learning approaches to develop automated CXR diagnostic models. In particular, we trained several Convolutional Neural Networks (CNN) on the CheXpert dataset, a large collection of more than 200k CXR labeled images. Then, we used the trained CNNs to compute embeddings of the CXR images, in order to train two sets of tree-based classifiers from them. Finally, we described and compared three ensembling strategies to combine together the classifiers trained. Rather than expecting some performance-wise benefits, our goal in this work is showing that the above two methodologies, i.e., the extraction of image embeddings and models ensembling, can be effective and viable to solve tasks that require medical imaging understanding. Our results in that perspective are encouraging and worthy of further investigation.

Edoardo Giacomello, Daniele Loiacono, Luca Mainardi

Deep Learning is a promising approach to either automate or simplify several tasks in the healthcare domain. In this work, we introduce SegAN-CAT, an approach to brain tumor segmentation in Magnetic Resonance Images (MRI), based on Adversarial Networks. In particular, we extend SegAN, successfully applied to the same task in a previous work, in two respects: (i) we used a different model input and (ii) we employed a modified loss function to train the model. We tested our approach on two large datasets, made available by the Brain Tumor Image Segmentation Benchmark (BraTS). First, we trained and tested some segmentation models assuming the availability of all the major MRI contrast modalities, i.e., T1-weighted, T1 weighted contrast-enhanced, T2-weighted, and T2-FLAIR. However, as these four modalities are not always all available for each patient, we also trained and tested four segmentation models that take as input MRIs acquired only with a single contrast modality. Finally, we proposed to apply transfer learning across different contrast modalities to improve the performance of these single-modality models. Our results are promising and show that not SegAN-CAT is able to outperform SegAN when all the four modalities are available, but also that transfer learning can actually lead to better performances when only a single modality is available.

Edoardo Giacomello, Pier Luca Lanzi, Daniele Loiacono

We applied Generative Adversarial Networks (GANs) to learn a model of DOOM levels from human-designed content. Initially, we analysed the levels and extracted several topological features. Then, for each level, we extracted a set of images identifying the occupied area, the height map, the walls, and the position of game objects. We trained two GANs: one using plain level images, one using both the images and some of the features extracted during the preliminary analysis. We used the two networks to generate new levels and compared the results to assess whether the network trained using also the topological features could generate levels more similar to human-designed ones. Our results show that GANs can capture intrinsic structure of DOOM levels and appears to be a promising approach to level generation in first person shooter games.

Antonio Umberto Aramini, Pier Luca Lanzi, Daniele Loiacono

The design of video game levels is a complex and critical task. Levels need to elicit fun and challenge while avoiding frustration at all costs. In this paper, we present a framework to assist designers in the creation of levels for 2D platformers. Our framework provides designers with a toolbox (i) to create 2D platformer levels, (ii) to estimate the difficulty and probability of success of single jump actions (the main mechanics of platformer games), and (iii) a set of metrics to evaluate the difficulty and probability of completion of entire levels. At the end, we present the results of a set of experiments we carried out with human players to validate the metrics included in our framework.

Daniele Loiacono, Luigi Cardamone, Pier Luca Lanzi

This manual describes the competition software for the Simulated Car Racing Championship, an international competition held at major conferences in the field of Evolutionary Computation and in the field of Computational Intelligence and Games. It provides an overview of the architecture, the instructions to install the software and to run the simple drivers provided in the package, the description of the sensors and the actuators.