Manolis Tsiknakis

Karim Lekadir, Aasa Feragen, Abdul Joseph Fofanah et al. · eth-zurich

Despite major advances in artificial intelligence (AI) for medicine and healthcare, the deployment and adoption of AI technologies remain limited in real-world clinical practice. In recent years, concerns have been raised about the technical, clinical, ethical and legal risks associated with medical AI. To increase real world adoption, it is essential that medical AI tools are trusted and accepted by patients, clinicians, health organisations and authorities. This work describes the FUTURE-AI guideline as the first international consensus framework for guiding the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI consortium was founded in 2021 and currently comprises 118 inter-disciplinary experts from 51 countries representing all continents, including AI scientists, clinicians, ethicists, and social scientists. Over a two-year period, the consortium defined guiding principles and best practices for trustworthy AI through an iterative process comprising an in-depth literature review, a modified Delphi survey, and online consensus meetings. The FUTURE-AI framework was established based on 6 guiding principles for trustworthy AI in healthcare, i.e. Fairness, Universality, Traceability, Usability, Robustness and Explainability. Through consensus, a set of 28 best practices were defined, addressing technical, clinical, legal and socio-ethical dimensions. The recommendations cover the entire lifecycle of medical AI, from design, development and validation to regulation, deployment, and monitoring. FUTURE-AI is a risk-informed, assumption-free guideline which provides a structured approach for constructing medical AI tools that will be trusted, deployed and adopted in real-world practice. Researchers are encouraged to take the recommendations into account in proof-of-concept stages to facilitate future translation towards clinical practice of medical AI.

Stefanos Gkikas, Manolis Tsiknakis

Automatic pain assessment plays a critical role for advancing healthcare and optimizing pain management strategies. This study has been submitted to the First Multimodal Sensing Grand Challenge for Next-Gen Pain Assessment (AI4PAIN). The proposed multimodal framework utilizes facial videos and fNIRS and presents a modality-agnostic approach, alleviating the need for domain-specific models. Employing a dual ViT configuration and adopting waveform representations for the fNIRS, as well as for the extracted embeddings from the two modalities, demonstrate the efficacy of the proposed method, achieving an accuracy of 46.76% in the multilevel pain assessment task.

Stefanos Gkikas, Chariklia Chatzaki, Manolis Tsiknakis

Pain is a complex phenomenon which is manifested and expressed by patients in various forms. The immediate and objective recognition of it is a great of importance in order to attain a reliable and unbiased healthcare system. In this work, we elaborate electrocardiography signals revealing the existence of variations in pain perception among different demographic groups. We exploit this insight by introducing a novel multi-task neural network for automatic pain estimation utilizing the age and the gender information of each individual, and show its advantages compared to other approaches.

Stefanos Gkikas, Manolis Tsiknakis

Pain assessment is essential in developing optimal pain management protocols to alleviate suffering and prevent functional decline in patients. Consequently, reliable and accurate automatic pain assessment systems are essential for continuous and effective patient monitoring. This study presents synthetic thermal videos generated by Generative Adversarial Networks integrated into the pain recognition pipeline and evaluates their efficacy. A framework consisting of a Vision-MLP and a Transformer-based module is utilized, employing RGB and synthetic thermal videos in unimodal and multimodal settings. Experiments conducted on facial videos from the BioVid database demonstrate the effectiveness of synthetic thermal videos and underline the potential advantages of it.

Stefanos Gkikas, Raul Fernandez Rojas, Manolis Tsiknakis

Pain is a manifold condition that impacts a significant percentage of the population. Accurate and reliable pain evaluation for the people suffering is crucial to developing effective and advanced pain management protocols. Automatic pain assessment systems provide continuous monitoring and support decision-making processes, ultimately aiming to alleviate distress and prevent functionality decline. This study introduces PainFormer, a vision foundation model based on multi-task learning principles trained simultaneously on 14 tasks/datasets with a total of 10.9 million samples. Functioning as an embedding extractor for various input modalities, the foundation model provides feature representations to the Embedding-Mixer, a transformer-based module that performs the final pain assessment. Extensive experiments employing behavioral modalities - including RGB, synthetic thermal, and estimated depth videos - and physiological modalities such as ECG, EMG, GSR, and fNIRS revealed that PainFormer effectively extracts high-quality embeddings from diverse input modalities. The proposed framework is evaluated on two pain datasets, BioVid and AI4Pain, and directly compared to 75 different methodologies documented in the literature. Experiments conducted in unimodal and multimodal settings demonstrate state-of-the-art performances across modalities and pave the way toward general-purpose models for automatic pain assessment. The foundation model's architecture (code) and weights are available at: https://github.com/GkikasStefanos/PainFormer.

Stefanos Gkikas, Ioannis Kyprakis, Manolis Tsiknakis

Pain is a complex and pervasive condition that affects a significant portion of the population. Accurate and consistent assessment is essential for individuals suffering from pain, as well as for developing effective management strategies in a healthcare system. Automatic pain assessment systems enable continuous monitoring, support clinical decision-making, and help minimize patient distress while mitigating the risk of functional deterioration. Leveraging physiological signals offers objective and precise insights into a person's state, and their integration in a multimodal framework can further enhance system performance. This study has been submitted to the Second Multimodal Sensing Grand Challenge for Next-Gen Pain Assessment (AI4PAIN). The proposed approach introduces Tiny-BioMoE, a lightweight pretrained embedding model for biosignal analysis. Trained on 4.4 million biosignal image representations and consisting of only 7.3 million parameters, it serves as an effective tool for extracting high-quality embeddings for downstream tasks. Extensive experiments involving electrodermal activity, blood volume pulse, respiratory signals, peripheral oxygen saturation, and their combinations highlight the model's effectiveness across diverse modalities in automatic pain recognition tasks. The model's architecture (code) and weights are available at https://github.com/GkikasStefanos/Tiny-BioMoE.

Stefanos Gkikas, Manolis Tsiknakis

The automatic estimation of pain is essential in designing an optimal pain management system offering reliable assessment and reducing the suffering of patients. In this study, we present a novel full transformer-based framework consisting of a Transformer in Transformer (TNT) model and a Transformer leveraging cross-attention and self-attention blocks. Elaborating on videos from the BioVid database, we demonstrate state-of-the-art performances, showing the efficacy, efficiency, and generalization capability across all the primary pain estimation tasks.

Stefanos Gkikas, Ioannis Kyprakis, Manolis Tsiknakis

Pain is a complex condition that affects a large portion of the population. Accurate and consistent evaluation is essential for individuals experiencing pain and supports the development of effective and advanced management strategies. Automatic pain assessment systems provide continuous monitoring, aid clinical decision-making, and aim to reduce distress while preventing functional decline. This study has been submitted to the Second Multimodal Sensing Grand Challenge for Next-Gen Pain Assessment (AI4PAIN). The proposed method introduces a pipeline that employs respiration as the input signal and integrates a highly efficient cross-attention transformer with a multi-windowing strategy. Extensive experiments demonstrate that respiration serves as a valuable physiological modality for pain assessment. Furthermore, results show that compact and efficient models, when properly optimized, can deliver strong performance, often surpassing larger counterparts. The proposed multi-window strategy effectively captures short-term and long-term features, along with global characteristics, enhancing the model's representational capacity.

Stefanos Gkikas, Ioannis Kyprakis, Manolis Tsiknakis

Pain is a multifaceted phenomenon that affects a substantial portion of the population. Reliable and consistent evaluation supports individuals experiencing pain and enables the development of effective and advanced management strategies. Automatic pain-assessment systems provide continuous monitoring, guide clinical decision-making, and aim to reduce distress while preventing functional decline. Incorporating physiological signals allows these systems to deliver objective, accurate insights into an individual's condition. This study has been submitted to the Second Multimodal Sensing Grand Challenge for Next-Gen Pain Assessment (AI4PAIN). The proposed method introduces a pipeline that employs electrodermal activity signals as the input modality. Multiple signal representations are generated and visualized as waveforms, which are then jointly presented within a unified multi-representation diagram. Extensive experiments using diverse processing and filtering techniques, along with various representation combinations, highlight the effectiveness of the approach. It consistently achieves comparable and, in several cases, superior results to traditional fusion methods, positioning it as a robust alternative for integrating different signal representations or modalities.

Ioannis Kyprakis, Vasileios Skaramagkas, Georgia Karanasiou et al.

Psychological stress is clinically relevant in cardio-oncology, yet it is typically assessed only through patient-reported outcome measures (PROMs) and is rarely integrated into continuous cardiotoxicity surveillance. We estimate perceived stress in an elderly, multicenter breast cancer cohort (CARDIOCARE) using multimodal wearable data from a smartwatch (physical activity and sleep) and a chest-worn ECG sensor. Wearable streams are transformed into heterogeneous visual representations, yielding a weakly supervised setting in which a single Perceived Stress Scale (PSS) score corresponds to many unlabeled windows. A lightweight pretrained mixture-of-experts backbone (Tiny-BioMoE) embeds each representation into 192-dimensional vectors, which are aggregated via attention-based multiple instance learning (MIL) to predict PSS at month 3 (M3) and month 6 (M6). Under leave-one-subject-out (LOSO) evaluation, predictions showed moderate agreement with questionnaire scores (M3: R^2=0.24, Pearson r=0.42, Spearman rho=0.48; M6: R^2=0.28, Pearson r=0.49, Spearman rho=0.52), with global RMSE/MAE of 6.62/6.07 at M3 and 6.13/5.54 at M6.

Ioannis Kyprakis, Vasileios Skaramagkas, Georgia Karanasiou et al.

Frailty and functional decline strongly influence treatment tolerance and outcomes in older patients with cancer, yet assessment is typically limited to infrequent clinic visits. We propose a multimodal wearable framework to estimate frailty-related functional change between visits in elderly breast cancer patients enrolled in the multicenter CARDIOCARE study. Free-living smartwatch physical activity and sleep features are combined with ECG-derived heart rate variability (HRV) features from a chest strap and organized into patient-horizon bags aligned to month 3 (M3) and month 6 (M6) follow-ups. Our innovation is an attention-based multiple instance learning (MIL) formulation that fuses irregular, multimodal wearable instances under real-world missingness and weak supervision. An attention-based MIL model with modality-specific multilayer perceptron (MLP) encoders with embedding dimension 128 aggregates variable-length and partially missing longitudinal instances to predict discretized change-from-baseline classes (worsened, stable, improved) for FACIT-F and handgrip strength. Under subject-independent leave-one-subject-out (LOSO) evaluation, the full multimodal model achieved balanced accuracy/F1 of 0.68 +/- 0.08/0.67 +/- 0.09 at M3 and 0.70 +/- 0.10/0.69 +/- 0.08 at M6 for handgrip, and 0.59 +/- 0.04/0.58 +/- 0.06 at M3 and 0.64 +/- 0.05/0.63 +/- 0.07 at M6 for FACIT-F. Ablation results indicated that smartwatch activity and sleep provide the strongest predictive information for frailty-related functional changes, while HRV contributes complementary information when fused with smartwatch streams.

Varvara Kalokyri, Nikolaos S. Tachos, Charalampos N. Kalantzopoulos et al.

The increasing integration of Artificial Intelligence (AI) into health and biomedical systems necessitates robust frameworks for transparency, accountability, and ethical compliance. Existing frameworks often rely on human-readable, manual documentation which limits scalability, comparability, and machine interpretability across projects and platforms. They also fail to provide a unique, verifiable identity for AI models to ensure their provenance and authenticity across systems and use cases, limiting reproducibility and stakeholder trust. This paper introduces the concept of the AI Model Passport, a structured and standardized documentation framework that acts as a digital identity and verification tool for AI models. It captures essential metadata to uniquely identify, verify, trace and monitor AI models across their lifecycle - from data acquisition and preprocessing to model design, development and deployment. In addition, an implementation of this framework is presented through AIPassport, an MLOps tool developed within the ProCAncer-I EU project for medical imaging applications. AIPassport automates metadata collection, ensures proper versioning, decouples results from source scripts, and integrates with various development environments. Its effectiveness is showcased through a lesion segmentation use case using data from the ProCAncer-I dataset, illustrating how the AI Model Passport enhances transparency, reproducibility, and regulatory readiness while reducing manual effort. This approach aims to set a new standard for fostering trust and accountability in AI-driven healthcare solutions, aspiring to serve as the basis for developing transparent and regulation compliant AI systems across domains.

Vasileios C. Pezoulas, Nikolaos S. Tachos, Eleni Georga et al.

In the rapidly evolving era of Artificial Intelligence (AI), synthetic data are widely used to accelerate innovation while preserving privacy and enabling broader data accessibility. However, the evaluation of synthetic data remains fragmented across heterogeneous metrics, ad-hoc scripts, and incomplete reporting practices. To address this gap, we introduce Synthetic Data Blueprint (SDB), a modular Pythonic based library to quantitatively and visually assess the fidelity of synthetic tabular data. SDB supports: (i) automated feature-type detection, (ii) distributional and dependency-level fidelity metrics, (iii) graph- and embedding-based structure preservation scores, and (iv) a rich suite of data visualization schemas. To demonstrate the breadth, robustness, and domain-agnostic applicability of the SDB, we evaluated the framework across three real-world use cases that differ substantially in scale, feature composition, statistical complexity, and downstream analytical requirements. These include: (i) healthcare diagnostics, (ii) socioeconomic and financial modelling, and (iii) cybersecurity and network traffic analysis. These use cases reveal how SDB can address diverse data fidelity assessment challenges, varying from mixed-type clinical variables to high-cardinality categorical attributes and high-dimensional telemetry signals, while at the same time offering a consistent, transparent, and reproducible benchmarking across heterogeneous domains.

Ioannis Kyprakis, Vasileios Skaramagkas, Iro Boura et al.

Parkinson's disease (PD) is a neurodegenerative disorder, manifesting with motor and non-motor symptoms. Depressive symptoms are prevalent in PD, affecting up to 45% of patients. They are often underdiagnosed due to overlapping motor features, such as hypomimia. This study explores deep learning (DL) models-ViViT, Video Swin Tiny, and 3D CNN-LSTM with attention layers-to assess the presence and severity of depressive symptoms, as detected by the Geriatric Depression Scale (GDS), in PD patients through facial video analysis. The same parameters were assessed in a secondary analysis taking into account whether patients were one hour after (ON-medication state) or 12 hours without (OFF-medication state) dopaminergic medication. Using a dataset of 1,875 videos from 178 patients, the Video Swin Tiny model achieved the highest performance, with up to 94% accuracy and 93.7% F1-score in binary classification (presence of absence of depressive symptoms), and 87.1% accuracy with an 85.4% F1-score in multiclass tasks (absence or mild or severe depressive symptoms).

Karim Lekadir, Richard Osuala, Catherine Gallin et al.

The recent advancements in artificial intelligence (AI) combined with the extensive amount of data generated by today's clinical systems, has led to the development of imaging AI solutions across the whole value chain of medical imaging, including image reconstruction, medical image segmentation, image-based diagnosis and treatment planning. Notwithstanding the successes and future potential of AI in medical imaging, many stakeholders are concerned of the potential risks and ethical implications of imaging AI solutions, which are perceived as complex, opaque, and difficult to comprehend, utilise, and trust in critical clinical applications. Addressing these concerns and risks, the FUTURE-AI framework has been proposed, which, sourced from a global multi-domain expert consensus, comprises guiding principles for increased trust, safety, and adoption for AI in healthcare. In this paper, we transform the general FUTURE-AI healthcare principles to a concise and specific AI implementation guide tailored to the needs of the medical imaging community. To this end, we carefully assess each building block of the FUTURE-AI framework consisting of (i) Fairness, (ii) Universality, (iii) Traceability, (iv) Usability, (v) Robustness and (vi) Explainability, and respectively define concrete best practices based on accumulated AI implementation experiences from five large European projects on AI in Health Imaging. We accompany our concrete step-by-step medical imaging development guide with a practical AI solution maturity checklist, thus enabling AI development teams to design, evaluate, maintain, and deploy technically, clinically and ethically trustworthy imaging AI solutions into clinical practice.

Dimitrios G. Zaridis, Eugenia Mylona, Nikolaos S. Tachos et al.

Prostate segmentation from magnetic resonance imaging (MRI) is a challenging task. In recent years, several network architectures have been proposed to automate this process and alleviate the burden of manual annotation. Although the performance of these models has achieved promising results, there is still room for improvement before these models can be used safely and effectively in clinical practice. One of the major challenges in prostate MR image segmentation is the presence of class imbalance in the image labels where the background pixels dominate over the prostate. In the present work we propose a DL-based pipeline for cropping the region around the prostate from MRI images to produce a more balanced distribution of the foreground pixels (prostate) and the background pixels and improve segmentation accuracy. The effect of DL-cropping for improving the segmentation performance compared to standard center-cropping is assessed using five popular DL networks for prostate segmentation, namely U-net, U-net+, Res Unet++, Bridge U-net and Dense U-net. The proposed smart-cropping outperformed the standard center cropping in terms of segmentation accuracy for all the evaluated prostate segmentation networks. In terms of Dice score, the highest improvement was achieved for the U-net+ and ResU-net++ architectures corresponding to 8.9% and 8%, respectively.