Recent advancements in artificial intelligence (AI) and the vast data generated by modern clinical systems have driven the development of AI solutions in medical imaging, encompassing image reconstruction, segmentation, diagnosis, and treatment planning. Despite these successes and potential, many stakeholders worry about the risks and ethical implications of imaging AI, viewing it as complex, opaque, and challenging to understand, use, and trust in critical clinical applications. The FUTURE-AI guideline for trustworthy AI in healthcare was established based on six guiding principles: Fairness, Universality, Traceability, Usability, Robustness, and Explainability. Through international consensus, a set of recommendations was defined, covering the entire lifecycle of medical AI tools, from design, development, and validation to regulation, deployment, and monitoring. In this paper, we describe how these specific recommendations can be instantiated in the domain of medical imaging, providing an overview of current best practices along with guidelines and concrete metrics on how those recommendations could be met, offering a valuable resource to the international medical imaging community.

Over the past five years, artificial intelligence (AI) has introduced new models and methods for addressing the challenges associated with the broader adoption of AI models and systems in medicine. This paper reviews recent advances in AI for medical image and video analysis, outlines emerging paradigms, highlights pathways for successful clinical translation, and provides recommendations for future work. Hybrid Convolutional Neural Network (CNN) Transformer architectures now deliver state-of-the-art results in segmentation, classification, reconstruction, synthesis, and registration. Foundation and generative AI models enable the use of transfer learning to smaller datasets with limited ground truth. Federated learning supports privacy-preserving collaboration across institutions. Explainable and trustworthy AI approaches have become essential to foster clinician trust, ensure regulatory compliance, and facilitate ethical deployment. Together, these developments pave the way for integrating AI into radiology, pathology, and wider healthcare workflows.

Developing AI models for digital pathology has traditionally relied on single-scale analysis of histopathology slides. However, a whole slide image is a rich digital representation of the tissue, captured at various magnification levels. Limiting our analysis to a single scale overlooks critical information, spanning from intricate high-resolution cellular details to broad low-resolution tissue structures. In this study, we propose a model-agnostic multiresolution feature aggregation framework tailored for the analysis of histopathology slides in the context of breast cancer, on a multicohort dataset of 2038 patient samples. We have adapted 9 state-of-the-art multiple instance learning models on our multi-scale methodology and evaluated their performance on grade prediction, TP53 mutation status prediction and survival prediction. The results prove the dominance of the multiresolution methodology, and specifically, concatenating or linearly transforming via a learnable layer the feature vectors of image patches from a high (20x) and low (10x) magnification factors achieve improved performance for all prediction tasks across domain-specific and imagenet-based features. On the contrary, the performance of uniresolution baseline models was not consistent across domain-specific and imagenet-based features. Moreover, we shed light on the inherent inconsistencies observed in models trained on whole-tissue-sections when validated against biopsy-based datasets. Despite these challenges, our findings underscore the superiority of multiresolution analysis over uniresolution methods. Finally, cross-scale analysis also benefits the explainability aspects of attention-based architectures, since one can extract attention maps at the tissue- and cell-levels, improving the interpretation of the model's decision.

The identification of the location of prostate cancer is of paramount importance for improved treatment. This process is strictly bonded with the accurate segmentation of the prostate gland and its zones, on MR images. In the present study, an ensemble of 3 deep learning models along with a Meta-learner module able to refine the outcomes of the models, is proposed (Transi-Net) to segment the prostate's transition zone. A method to quantify the model's uncertainty is introduced to measure the confidence of an architecture with respect to its final decision. The backbone of Transi-Net consist the original U-net, Dense2U-net and Bridged U-net models. The proposed model showcased significant improvement in comparison with its base components as well as an independent model, the USE-Net, while it was proven more confident about its decision. The proposed model resulted in an improvement of 5%, 3%, 3% and 4% for Sensitivity, Balanced Accuracy, Dice Score and Rand Error Index respectively, compared to the second best, USE-Net.

Breast cancer (BC) is the most common cancer in women in Europe and worldwide, with a high prevalence in middle-aged and older women. The last years, the evolution in the existing treatment approaches have contributed to improved clinical outcomes and survival rates. Nevertheless, BC therapy-related cardiotoxicity, poses a severe impact in the short- and long-term Quality of Life (QoL) and associated survival of the BC patients. This study demonstrates how the CARDIOCARE platform and the developed risk stratification models provides healthcare professionals with a valuable tool for effectively managing BC patients, preventing treatment induced cardiotoxicity and improving their QoL. This is accomplished through the integration of multi-source patient-specific data from patient-oriented mobile applications and wearable sensors, and by the employment of beyond the state-of-the-art data mining and machine learning approaches.

Informal care is fundamental in the wellbeing and resilience of elderly and people with chronic conditions. However, solutions for the effective collaboration of healthcare professionals, patients and informal carers are not yet widely available. CareKeeper builds on a state-of-the-art personal health system, augmenting it with Artificial Intelligence and Big Data technologies, to boost informal care coordination. In this paper we report on the design of the platform with the aim of providing a light-weighted communication solution to support practical challenges about sharing the responsibility of caring, such as the frequency of visits, support to routinely activities and timely intervention in case of emergency and need.

Automatic segmentation of the prostate peripheral zone on Magnetic Resonance Images (MRI) is a necessary but challenging step for accurate prostate cancer diagnosis. Deep learning (DL) based methods, such as U-Net, have recently been developed to segment the prostate and its' sub-regions. Nevertheless, the presence of class imbalance in the image labels, where the background pixels dominate over the region to be segmented, may severely hamper the segmentation performance. In the present work, we propose a DL-based preprocessing pipeline for segmenting the peripheral zone of the prostate by cropping unnecessary information without making a priori assumptions regarding the location of the region of interest. The effect of DL-cropping for improving the segmentation performance was compared to the standard center-cropping using three state-of-the-art DL networks, namely U-net, Bridged U-net and Dense U-net. The proposed method achieved an improvement of 24%, 12% and 15% for the U-net, Bridged U-net and Dense U-net, respectively, in terms of Dice score.

As the field of brain monitoring is evolving rapidly, there is an increasing demand of finding innovative ways to handle relevant signals. Especially electroencephalogram (EEG) signals provide a non-invasive way of diagnostic inference of brain's functionality. Nevertheless, EEG signals are often corrupted by impulsive noise, thus prior denoising is required for accurate analysis and decision making. On the other hand, EEG signals admit naturally a representation in the form of graphs, with the electrodes corresponding to the nodes of the graph and the edges expressing the connectivity strength. To this end, graph signal processing (GSP) is a versatile tool, which enables the representation and analysis of graph-structured signals, whose interdependencies are encoded in the form of an appropriate adjacency matrix. To address the denoising of graph-structured signals, under impulsive noise conditions, this work introduces a regularized graph filtering scheme based on fractional lower order moments, coupled with distinct adjacency matrices inspired both by statistical approaches and visibility graphs that are better capable of capturing the topological and functional connectivity between the distinct nodes. The experimental evaluation on real EEG signals recorded in epileptic and non-epileptic seizures, reveals the effects of the adjacency matrix choice on the denoising performance.

Emotional stress detection can be performed analyzing different facial parameters. This paper focuses on the automated identification of facial Action Units (AU) as quantitative indices in order to discriminate between neutral and stress/anxiety state. Thus, a model for automatic recognition of facial action units is proposed being trained in two available annotated facial datasets, the UNBC and the BOSPHORUS datasets. Facial features, both geometric (non-rigid deformations of 3D shape of AAM landmarks) and appearance (Histograms of Oriented Gradients) were extracted. The intensity of each AU was regressed using Support Vector Regression (SVR). The corresponding models of each dataset were fused to a combined model. This combined model was applied to the experimental dataset (SRD'15) containing neutral states and inducing stressful states related to four types of stress. The results indicate that there are specific AU relevant to stress and the AU intensity are significant increased during stress leading to a more expressive human face.

Recording of patient-reported outcomes (PROs) enables direct measurement of the experiences of patients with chronic conditions, including cancer; thus, PROs are a critical element of high quality, person-centered care for cancer patients. A growing body of literature reports on the feasibility of using electronic tools for the collection of Patient reported Outcomes (ePROs), although the usability of available solutions does affect their acceptance and use. In parallel, recent advancement in artificial intelligence, machine learning and speech recognition have led to the growing interest in conversational agents, i.e. software applications that mimic written or spoken human speech. In the present manuscript we provide a review of current developments regarding the implementation of conversational agents and their application in the domain of palliative care for oncology patients and also present (i) a methodology for the implementation of a conversational agent able to collect ePRO health data and (ii) initial evaluation results from a relevant feasibility study. Our approach differs from other available systems since the conversational agent reported in the present work is not based on rules, but rather uses machine learning algorithms and more specifically recurrent neural networks (RNN) for identifying appropriate answers. Evaluation results of user experience provided promising results and highlight that users gave positive responds when interacting with the system. Based on the User Experience Questionnaire, pragmatic quality and overall quality were categorized as excellent and hedonic quality was categorized as good. The result of this research can be used as reference for the future development and improvement of the conversational agents in the healthcare domain.

Coping with breast cancer and its consequences has now become a major socioeconomic challenge. The BOUNCE EU H2020 project aims at building a quantitative mathematical model of factors associated with optimal adjustment capacity to cancer. This paper gives an overview of the project targets and on the algorithmic methods focusing on modeling the psychological resilience trajectories during breast cancer treatment.

Radiomics-based studies have created an unprecedented momentum in computational medical imaging over the last years by significantly advancing and empowering correlational and predictive quantitative studies in numerous clinical applications. An important element of this exciting field of research especially in oncology is multi-scale texture analysis since it can effectively describe tissue heterogeneity, which is highly informative for clinical diagnosis and prognosis. There are however, several concerns regarding the plethora of radiomics features used in the literature especially regarding their performance consistency across studies. Since many studies use software packages that yield multi-scale texture features it makes sense to investigate the scale-space performance of texture candidate biomarkers under the hypothesis that significant texture markers may have a more persistent scale-space performance. To this end, this study proposes a methodology for the extraction of Gabor multi-scale and orientation texture DCE-MRI radiomics for predicting breast cancer complete response to neoadjuvant therapy. More specifically, a Gabor filter bank was created using four different orientations and ten different scales and then first-order and second-order texture features were extracted for each scale-orientation data representation. The performance of all these features was evaluated under a generalized repeated cross-validation framework in a scale-space fashion using extreme gradient boosting classifiers.

Palliative care is offered along with primary treatment to improve the quality of life of the patient by relieving the symptoms and stress of a serious illness such as cancer. As per modern definitions, palliative care is appropriate at any age and at any stage of the illness, regardless of the eventual outcome. Patient-reported outcomes (PRO), i.e., health status measurements reported directly by the patients or their proxies, and especially their availability in electronic form (ePROs), are gradually gaining popularity as building blocks of innovative palliative care interventions. This paper presents MyPal, an EC-funded collaborative research project that aims to exploit advanced eHealth technologies to develop and evaluate two novel ePRO-based general palliative care interventions for cancer patients. In particular, the paper presents: (1) a short overview of MyPal; (2) the target populations, i.e., adults suffering from chronic lymphocytic leukemia (CLL) or myelodysplastic syndromes (MDS), and children with solid or hematologic malignancies; (3) the ePRO-based interventions being designed for the target populations, (4) the eHealth platform for delivering the interventions under development, and (5) the international, multi-center clinical studies to be conducted for assessing these interventions, i.e., a randomized controlled trial (RCT) and an observational study for adults and children, respectively.

This paper presents a method for reducing the Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) examination time based on the mathematical framework of sparse representations. The aim is to undersample the b-values used for DW-MRI image acquisition which reflect the strength and timing of the gradients used to generate the DW-MRI images since their number defines the examination time. To test our method we investigate whether the undersampled DW-MRI data preserve the same accuracy in terms of extracted imaging biomarkers. The main procedure is based on the use of the k-Singular Value Decomposition (k-SVD) and the Orthogonal Matching Pursuit (OMP) algorithms, which are appropriate for the sparse representations computation. The presented results confirm the hypothesis of our study as the imaging biomarkers extracted from the sparsely reconstructed data have statistically close values to those extracted from the original data. Moreover, our method achieves a low reconstruction error and an image quality close to the original.

Breast cancer is the most common cancer disease in women and is rapidly becoming a chronic illness due recent advances in treatment methods. As such, coping with cancer has become a major socio-economic challenge leading to an increasing need for predicting resilience of women to the variety of stressful experiences and practical challenges they face. In this paper, we present the data infrastructure developed for this purpose, demonstrating the various components that will contribute to the developing the resilience trajectory predictor. Special emphasis is given to the semantic tier, presenting the project solution already implemented for effectively collecting, ingesting, cleaning, modelling and processing data that will be used throughout the lifetime of the project.

Evolutionary algorithms have been used recently as an alternative in image registration, especially in cases where the similarity function is non‐convex with many local optima. However, their drawback is that they tend to be computationally expensive. Trying to avoid local minima can increase the computational cost. The purpose of authors’ research is to minimise the duration of the image registration process. This paper presents a method to minimise the computational cost by introducing a machine learning–based variant of Harmony Search. To this end, a series of machine‐learning regression methods are tested in order to find the most appropriate that minimises the cost without degrading the quality of the results. The best regression method is then incorporated in the optimisation process and is compared with two well‐known ITK image registration methods. The comparison of authors’ image registration method with ITK concerns both the quality of the results and the duration of the registration experiments. The comparison is done on a set of random image pairs of various sources (e.g. medical or satellite images), and the encouraging results strongly indicate that authors’ method can be used in a variety of image registration applications producing quality results in significantly less time.

Automatic depression assessment based on visual cues is a rapidly growing research domain. The present exhaustive review of existing approaches as reported in over sixty publications during the last ten years focuses on image processing and machine learning algorithms. Visual manifestations of depression, various procedures used for data collection, and existing datasets are summarized. The review outlines methods and algorithms for visual feature extraction, dimensionality reduction, decision methods for classification and regression approaches, as well as different fusion strategies. A quantitative meta-analysis of reported results, relying on performance metrics robust to chance, is included, identifying general trends and key unresolved issues to be considered in future studies of automatic depression assessment utilizing visual cues alone or in combination with vocal or verbal cues.

MRI Imaging biomarkers (IBs) have the potential to deliver quantitative cancer descriptors of pathophysiology for non-invasively screening, diagnosing, and monitoring cancer patients across the cancer continuum. Despite a worldwide effort to standardize IBs involving major cancer organizations, significant variability of MR-based imaging biomarker across sites still hampers their clinical translation calling for more research in the field. To this end, in the present study quantitative and semi-quantitative approaches for perfusion biomarkers are compared in MRI data from three different cancer types. In particular, Ktrans a widely used but often variable across sites candidate biomarker is compared to a semi-quantitative perfusion MRI imaging biomarker (Wash-in WIN) in patients with breast, head, and neck and soft tissue sarcoma. Our results demonstrated a linear relationship between WIN and Ktrans in all cancer patients groups when a goodness of fit (high R̅2) criterion for ensuring adequate data quality and accuracy is met. This consistent correlation across three different cancer types indicates that the proposed semi-quantitative perfusion MRI IB can be a simpler, more robust and reproducible alternative to Ktrans for quantitative perfusion studies in oncology.

Imaging biomarkers (IBs) play a critical role in the clinical management of breast cancer (BRCA) patients throughout the cancer continuum for screening, diagnosis, and therapy assessment, especially in the neoadjuvant setting. However, certain model-based IBs suffer from significant variability due to the complex workflows involved in their computation, whereas model-free IBs have not been properly studied regarding clinical outcome. In this study, IBs from 35 BRCA patients who received neoadjuvant chemotherapy (NAC) were extracted from dynamic contrast-enhanced MR imaging (DCE-MRI) data with two different approaches, a model-free approach based on pattern recognition (PR), and a model-based one using pharmacokinetic compartmental modeling. Our analysis found that both model-free and model-based biomarkers can predict pathological complete response (pCR) after the first cycle of NAC. Overall, eight biomarkers predicted the treatment response after the first cycle of NAC, with statistical significance (p-valueep(AUC 73.4%) from the model-based approach. Moreover, the 80th percentile of ve achieved the highest pCR prediction at baseline with AUC 78.5%. The results suggest that the model-free DCE-MRI IBs could be a more robust alternative to complex, model based ones such as kepand favor the hypothesis that the PR image-derived hypoxic image component captures actual tumor hypoxia information able to predict BRCA NAC outcome.

Deep learning (DL) architectures have opened new horizons in medical image analysis attaining unprecedented performance in tasks such as tissue classification and segmentation as well as prediction of several clinical outcomes. In this paper, we propose and evaluate a novel three-dimensional (3-D) convolutional neural network (CNN) designed for tissue classification in medical imaging and applied for discriminating between primary and metastatic liver tumors from diffusion weighted MRI (DW-MRI) data. The proposed network consists of four consecutive strided 3-D convolutional layers with 3 × 3 × 3 kernel size and rectified linear unit (ReLU) as activation function, followed by a fully connected layer with 2048 neurons and a Softmax layer for binary classification. A dataset comprising 130 DW-MRI scans was used for the training and validation of the network. To the best of our knowledge this is the first DL solution for the specific clinical problem and the first 3-D CNN for cancer classification operating directly on whole 3-D tomographic data without the need of any preprocessing step such as region cropping, annotating, or detecting regions of interest. The classification performance results, 83% (3-D) versus 69.6% and 65.2% (2-D), demonstrated significant tissue classification accuracy improvement compared to two 2-D CNNs of different architectures also designed for the specific clinical problem with the same dataset. These results suggest that the proposed 3-D CNN architecture can bring significant benefit in DW-MRI liver discrimination and potentially, in numerous other tissue classification problems based on tomographic data, especially in size-limited, disease-specific clinical datasets.

The main purpose of this study is to analyze the intrinsic tumor physiologic characteristics in patients with sarcoma through model-free analysis of dynamic contrast enhanced MR imaging data (DCE-MRI). Clinical data were collected from three patients with two different types of histologically proven sarcomas who underwent conventional and advanced MRI examination prior to excision. An advanced matrix factorization algorithm has been applied to the data, resulting in the identification of the principal time-signal uptake curves of DCE-MRI data, which were used to characterize the physiology of the tumor area, described by three different perfusion patterns i.e. hypoxic, well-perfused and necrotic one. The performance of the algorithm was tested by applying different initialization approaches with subsequent comparison of their results. The algorithm was proven to be robust and led to the consistent segmentation of the tumor area in three regions of different perfusion, i.e. well-perfused, hypoxic and necrotic. Results from the model-free approach were compared with a widely used pharmacokinetic (PK) model revealing significant correlations.

The article Pattern recognition and pharmacokinetic methods on DCE-MRI data for tumor hypoxia mapping in sarcoma, written by M. Venianaki, O. Salvetti, E. de Bree, T. Maris, A. Karantanas, E. Kontopodis, K. Nikiforaki, K. Marias, was originally published electronically without open access.

Cancer research has led to more cancer patients being cured, and many more enabled to live with their cancer. As such, some cancers are now considered a chronic disease, where patients and their families face the challenge to take an active role in their own care and in some cases in their treatment. To this direction the iManageCancer project aims to provide a cancer specific self-management platform designed according to the needs of patient groups while focusing, in parallel, on the wellbeing of the cancer patient. In this paper, we present the use-case requirements collected using a survey, a workshop and the analysis of three white papers and then we explain the corresponding system architecture. We describe in detail the main technological components of the designed platform, show the current status of development and we discuss further directions of research.

A person's well-being status is reflected by their face through a combination of facial expressions and physical signs. The SEMEOTICONS project translates the semeiotic code of the human face into measurements and computational descriptors that are automatically extracted from images, videos, and three-dimensional scans of the face. SEMEOTICONS developed a multisensory platform in the form of a smart mirror to identify signs related to cardio-metabolic risk. The aim was to enable users to self-monitor their well-being status over time and guide them to improve their lifestyle. Significant scientific and technological challenges have been addressed to build the multisensory mirror, from touchless data acquisition, to real-time processing and integration of multimodal data.

In the recent years personal health monitoring systems have been gaining popularity, both as a result of the pull from the general population, keen to improve well-being and early detection of possibly serious health conditions and the push from the industry eager to translate the current significant progress in computer vision and machine learning into commercial products. One of such systems is the Wize Mirror, built as a result of the FP7 funded SEMEOTICONS (SEMEiotic Oriented Technology for Individuals CardiOmetabolic risk self-assessmeNt and Self-monitoring) project. The project aims to translate the semeiotic code of the human face into computational descriptors and measures, automatically extracted from videos, multispectral images, and 3D scans of the face. The multisensory platform, being developed as the result of that project, in the form of a smart mirror, looks for signs related to cardio-metabolic risks. The goal is to enable users to self-monitor their well-being status over time and improve their life-style via tailored user guidance. This paper is focused on the description of the part of that system, utilising computer vision and machine learning techniques to perform 3D morphological analysis of the face and recognition of psycho-somatic status both linked with cardio-metabolic risks. The paper describes the concepts, methods and the developed implementations as well as reports on the results obtained on both real and synthetic datasets.

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers' exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes.

Demand for analyzing very large datasets is increasing, especially with the introduction of chromatin immunoprecipitation sequencing which is a recent method of Next Generation Sequencing used to analyze protein interactions with DNA. The development of new technologies is revolutionizing genome-wide analysis and scientists' abilities to have a better understanding of the biological meaning but inferring gene regulatory networks from such data is still a major challenge in systems biology. Complex reactions at the molecular level in living cells and such knowledge, as it relates to specific phenotype, necessarily implies that a key molecular target should be considered within the framework of its gene regulatory network. The objective of our study is to explore the effect of proteins under specific conditions (e.g. treatment or starvation), in functional sub-pathways for specific phenotype. Using public microarray expression datasets for glioma and the KEGG human gene regulatory networks as proof of concept, we identified disrupted sub-paths due to STAT3 on functional glioma pathways. We expect that the proposed algorithmic approach could aid researchers to determine the biological relevance of the binding sites over functional sub-paths and provide insights for new disease treatments.

Significant Virtual Physiological Human efforts and projects have been concerned with cancer modeling, especially in the European Commission Seventh Framework research program, with the ambitious goal to approach personalized cancer simulation based on patient-specific data and thereby optimize therapy decisions in the clinical setting. However, building realistic in silico predictive models targeting the clinical practice requires interactive, synergetic approaches to integrate the currently fragmented efforts emanating from the systems biology and computational oncology communities all around the globe. To further this goal, we propose an intelligent graphical workflow planning system that exploits the multiscale and modular nature of cancer and allows building complex cancer models by intuitively linking/interchanging highly specialized models. The system adopts and extends current standardization efforts, key tools, and infrastructure in view of building a pool of reliable and reproducible models capable of improving current therapies and demonstrating the potential for clinical translation of these technologies.

This paper outlines the major components and function of the technologically integrated oncosimulator developed primarily within the Advancing Clinico Genomic Trials on Cancer (ACGT) project. The Oncosimulator is defined as an information technology system simulating in vivo tumor response to therapeutic modalities within the clinical trial context. Chemotherapy in the neoadjuvant setting, according to two real clinical trials concerning nephroblastoma and breast cancer, has been considered. The spatiotemporal simulation module embedded in the Oncosimulator is based on the multiscale, predominantly top-down, discrete entity-discrete event cancer simulation technique developed by the In Silico Oncology Group, National Technical University of Athens. The technology modules include multiscale data handling, image processing, invocation of code execution via a spreadsheet-inspired environment portal, execution of the code on the grid, and the visualization of the predictions. A refining scenario for the eventual coupling of the oncosimulator with immunological models is also presented. Parameter values have been adapted to multiscale clinical trial data in a consistent way, thus supporting the predictive potential of the oncosimulator. Indicative results demonstrating various aspects of the clinical adaptation and validation process are presented. Completion of these processes is expected to pave the way for the clinical translation of the system.

The digital avatar is a vision for the digital representation of personal health status in body centric views. It is designed as an integrated facility that allows collection of, access to and sharing to life-long and consistent data. A number of Virtual Physiological Human (VPH) communities have started the movement to this direction by creating a digital patient road-map and by supporting data sharing infrastructures. As an innovative concept, the impact of digital patient and avatar to personalized medicine and treatment is yet to be clear. This requires a focused and concerted effort in addressing various questions regarding user perspective, use cases and scenarios. This paper presents use cases and future scenarios realizing the vision for the digital avatar as well as architectural consideration for the envisaged platform.

The generation of “virtual twins” of patients (Avatars) through integration of multiscale data gained from both the clinical profile of the patient and - omics tools, could create an appropriate environment for stratification of patients in fitting cohorts of “virtual populations”. Physiologically based pharmacokinetic & pharmacodynamic (PB/PK/PD) models as in silico clinical trial tools can estimate the PK/PD profiles in specific populations. In this work we discuss examples of how patient Avatars could be exploited in the context of in silico clinical trials and help in identifying novel biomarkers for personalized diagnosis. The PB/PK/PD models, neuroimaging and - omics data, may be fused together to further advance current decision making processes in clinical practice.

Personalized medicine refers to the tailoring of treatment to the individual characteristics of a patient. Part of the personalized medicine is the patient profiling and the communicative relation between physician and patient. The ways of exchanging information, the nature of the information itself and the information assimilation capabilities of the patient can assist the physicians to have a better understanding. Taking advantage of these information sources, a smart environment could be implemented. This environment will be able to act as a decision support infrastructure to support the communication, interaction and information delivery process from the doctor to the patient. A prerequisite of personalized delivery of information and intelligent guidance of the patient into his/her treatment plans is our ability to develop an appropriate and accurate profile of the patient. In this paper we present a collaborative platform which will empower patient with knowledge about his/her health condition and at the same time it will assist the physician to have a better understanding about the patient's unique psychological profile. We also introduce the p-medicine project and its vision in the field of personalized medicine and show project's approach on patient empowerment.

The ongoing need of IT support for advancing personalized medicine has led to a plethora of needs for developing new computational algorithms, informatics resource management infrastructures and tools for extracting patient specific clinico-genomic information, and more recently, predicting and optimizing the therapeutic outcome for the individual patient within the EC VPH initiative. This has led to an unprecedented explosion in proposed tools and models for personalized medicine which in turn need specific frameworks for categorizing, querying and accessing such resources in an interoperable and standardized fashion. The proposed personalized medicine workbench is part of the EC funded p-medicine project and aims to create a semantically annotated repository of tools specific to the advancement of personalized medicine by addressing the project's clinical scenarios. Central to this development is the inclusion of a wide range of tools for personalized medicine encompassing biostatistics, bioinformatics, multi-scale predictive modeling and image analysis clinical applications.

Cancer cells inefficiently produce energy through glycolysis even in ample oxygen, a phenomenon known as “aerobic glycolysis”. A characteristic of the rapid and incomplete catabolism of glucose is the secretion of lactate. Genome-scale metabolic models have been recently employed to describe the glycolytic phenotype of highly proliferating human cancer cells. Genome-scale models describe genotype-phenotype relations revealing the full extent of metabolic capabilities of genotypes under various environmental conditions. The importance of these approaches in understanding some aspects of cancer complexity, as well as in cancer diagnostics and individualized therapeutic schemes related to metabolism is evident. Based on previous metabolic models, we explore the metabolic capabilities and rerouting that occur in cancer metabolism when we apply a strategy that allows near optimal growth solution while maximizing lactate secretion. The simulations show that slight deviations around the optimal growth are sufficient for adequate lactate release and that glucose uptake and lactate secretion are correlated at high proliferation rates as it has been observed. Inhibition of lactate dehydrogenase-A, an enzyme involved in the conversion of pyruvate to lactate, substantially reduces lactate release. We also observe that activating specific reactions associated with the migration-related PLCγ enzyme, the proliferation rate decreases. Furthermore, we incorporate flux constraints related to differentially expressed genes in Glioblastoma Multiforme in an attempt to construct a Glioblastoma-specific metabolic model and investigate its metabolic capabilities across different glucose uptake bounds.

Improving the initial diagnosis and the assessment of response to treatment in malignant gliomas, while avoiding invasive methods as much as justifiable, is one major aspect actual research is focusing on. Imaging studies are used to calculate tumor volume and define vital, necrotic and cystic areas within a tumor. Though the visual interpretation of magnetic resonance (MR) images is based on qualitative observation of variation in signal intensity, a correlation of signal intensities with histological features of a tumor is not possible. Better methods are needed for a reliable interpretation of follow-up studies in single patients. Histograms of signal intensities might serve as a method adding quantitative data to the description of a tumor. Using DoctorEye software, tumors can be easily rendered and histograms of the signal intensities within a tumor as well as mean and median signal intensities are possible to calculate. Our results in glioblastoma suggest that these histograms are an innovative method of gaining new tumor-specific information without performing additional investigations in a patient. It can be an additional diagnostic tool in differentiating various intracranial lesions from each other, as well as in assessing response to treatment or progression of malignant glioma.

Glioma, especially glioblastoma, is a leading cause of brain cancer fatality involving highly invasive and neoplastic growth. Diffusive models of glioma growth use variations of the diffusion-reaction equation in order to simulate the invasive patterns of glioma cells by approximating the spatiotemporal change of glioma cell concentration. The most advanced diffusive models take into consideration the heterogeneous velocity of glioma in gray and white matter, by using two different discrete diffusion coefficients in these areas. Moreover, by using diffusion tensor imaging (DTI), they simulate the anisotropic migration of glioma cells, which is facilitated along white fibers, assuming diffusion tensors with different diffusion coefficients along each candidate direction of growth. Our study extends this concept by fully exploiting the proportions of white and gray matter extracted by normal brain atlases, rather than discretizing diffusion coefficients. Moreover, the proportions of white and gray matter, as well as the diffusion tensors, are extracted by the respective atlases; thus, no DTI processing is needed. Finally, we applied this novel glioma growth model on real data and the results indicate that prognostication rates can be improved.

Glioma is one of the most aggressive types of brain tumor. Several mathematical models have been developed during the past two decades, toward simulating the mechanisms that govern the development of glioma. The most common models use the diffusion-reaction equation (DRE) for simulating the spatiotemporal variation of tumor cell concentration. Nevertheless, despite the applications presented, there has been little work on studying the details of the mathematical solution and implementation of the 3-D diffusion model and presenting a qualitative analysis of the algorithmic results. This paper presents a complete mathematical framework on the solution of the DRE using different numerical schemes. This framework takes into account all characteristics of the latest models, such as brain tissue heterogeneity, anisotropic tumor cell migration, chemotherapy, and resection modeling. The different numerical schemes presented have been evaluated based upon the degree to which the DRE exact solution is approximated. Experiments have been conducted both on real datasets and a test case for which there is a known algebraic expression of the solution. Thus, it is possible to calculate the accuracy of the different models.

This paper presents the work of our group concerning cancer image analysis and modeling. The adopted strategy aims to build a complete system for analysis and visualization of DICOM tomographic data, offering a variety of annotation or automatic segmentation tools as well as tools for tumor growth simulation and visualization.

Tomographic reconstruction of fluorescence optical projection tomography (OPT) data is usually performed using the standard filtered back projection (FBP) algorithm. However, there are several physical aspects of fluorescence OPT that pose major challenges for the FBP algorithm. These include blurring, and the fact that for an isotropically emitting point source (or fluorophore), the power received by an objective aperture decreases with the inverse square of the distance to the source. These two effects are shown to result in qualitative and quantitative inaccuracies in fluorescence OPT reconstructions obtained using standard FBP. A model of image formation is developed which includes the effects of isotropic emission and blurring. The model is used to calculate a probabilistic system matrix for use in the maximum likelihood expectation maximisation algorithm, which leads to reconstructions that are both qualitatively superior and quantitatively correct.

DNA microarrays have demonstrated an excellent potential in correlating specific gene expression profiles to specific conditions. However, they are affected by inherent noise. This paper presents a two-stage approach for noise removal that processes the additive and the multiplicative noise component. The proposed approach first decomposes the signal by a multiresolution transform and then accounts for both the multiscale correlation of the subband decompositions and their heavy-tailed statistics. Real microarray images have been processed by the proposed method and its improved performance is shown through quantitative measures and qualitative visual evaluation.

This paper presents a novel platform for image retrieval based on a two-level architecture inspired from human cognitive mechanisms. These two levels provide both generic similarity and semantic information related to special characteristics. Although the proposed architecture can be customized for any content-based image retrieval application, our work is focused on medical images and more specifically on brain MRI data. Our main motivation is that in medical applications, it is crucial to be able to combine in an efficient way, image similarity with specific, semantics related to pathology in order to provide the user with relevant cases and aid diagnosis. A description of the architecture and function of the proposed CBIR platform is presented, as well as specific details for the application to brain MRI retrieval

In this paper, we present a two-stage algorithm for mammogram registration, the geometrical alignment of mammogram sequences. The rationale behind this paper stems from the intrinsic difficulties in comparing mammogram sequences. Mammogram comparison is a valuable tool in national breast screening programs as well as in frequent monitoring and hormone replacement therapy (HRT). The method presented in this paper aims to improve mammogram comparison by estimating the underlying geometric transformation for any mammogram sequence. It takes into consideration the various temporal changes that may occur between successive scans of the same woman and is designed to overcome the inconsistencies of mammogram image formation.

In vivo fluorescence molecular imaging and tomography has facilitated monitoring of genomics and proteomics over time and on the same animal. A highly important issue, however, has been the robust registration of animals imaged at different time points to obtain accurate description of activity and location. This paper presents a method for aligning temporal data of small animals based on surface anatomical features and improving the accuracy of monitoring fluorophore distribution. The method can account for differences in the positioning and compression of small animals and can be extended to three-dimensional as well as to other imaging modalities.