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Abstract Purpose The purpose of this study was to correlate diffusion and perfusion quantitative and semi-quantitative MR parameters, on patients with peripheral arterial disease. In addition, we investigated which perfusion model better describes the behavior of the dynamic contrast-enhanced (DCE) MR data signal on ischemic regions of the lower limb. Methods Linear and nonlinear least squares algorithms, were incorporated for the quantification of the parameters through a variety of widely used models, able to extract physiological information from each imaging technique. All numerical calculations were implemented in Python 3.5 and include the: Intra voxel incoherent motion for diffusion and Patlak's, Extended Toft's and Gamma Capillary Transit time (GCTT) models for perfusion MRI. Results Our initial voxel by voxel correlation analysis didn't show any significant correlation based on the Pearson's Correlation metric between diffusion and perfusion parameters. To account for the inherited noise from the raw data, a Gaussian filter was applied to the parametric maps in order for the data to be comparable. By repeating our analysis in the filtered image maps, a good correlation (>0.5) of diffusion and perfusion parameters was achieved. Conclusions Perfusion and diffusion MRI quantitative and semi-quantitative parameters can be obtained through a variety of physiological-pharmacokinetic models. This paper compares most of the widely-known models and parameters in both techniques with data from patients with peripheral arterial disease. Initial analysis showed no correlation in the perfusion parametric maps of DWI and DCE MRI data but a good correlation was obtained after smoothing the parametric maps indicating that perfusion information could be obtained from diffusion MRI images in patients with peripheral arterial disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the performance of four diffusion models, including mono and bi-exponential both Gaussian and non-Gaussian models, in diffusion weighted imaging of rectal cancer. Material and methods: Nineteen patients with rectal adenocarcinoma underwent MRI examination of the rectum before chemoradiation therapy including a 7 b-value diffusion sequence (0, 25, 50, 100, 500, 1000 and 2000 s/mm2) at a 1.5T scanner. Four different diffusion models including mono- and bi-exponential Gaussian (MG and BG) and non-Gaussian (MNG and BNG) were applied on whole tumor volumes of interest. Two different statistical criteria were recruited to assess their fitting performance, including the adjusted-R2 and Root Mean Square Error (RMSE). To decide which model better characterizes rectal cancer, model selection was relied on Akaike Information Criteria (AIC) and F-ratio. Results: All candidate models achieved a good fitting performance with the two most complex models, the BG and the BNG, exhibiting the best fitting performance. However, both criteria for model selection indicated that the MG model performed better than any other model. In particular, using AIC Weights and F-ratio, the pixel-based analysis demonstrated that tumor areas better described by the simplest MG model in an average area of 53% and 33%, respectively. Non-Gaussian behavior was illustrated in an average area of 37% according to the F-ratio, and 7% using AIC Weights. However, the distributions of the pixels best fitted by each of the four models suggest that MG failed to perform better than any other model in all patients, and the overall tumor area. Conclusion: No single diffusion model evaluated herein could accurately describe rectal tumours. These findings probably can be explained on the basis of increased tumour heterogeneity, where areas with high vascularity could be fitted better with bi-exponential models, and areas with necrosis would mostly follow mono-exponential behavior. [ABSTRACT FROM AUTHOR]

Applying diffusive models for simulating the spatiotemporal change of concentration of tumour cells is a modern application of predictive oncology. Diffusive models are used for modelling glioblastoma, the most aggressive type of glioma. This paper presents the results of applying a linear quadratic model for simulating the effects of radiotherapy on an advanced diffusive glioma model. This diffusive model takes into consideration the heterogeneous velocity of glioma in gray and white matter and the anisotropic migration of tumor cells, which is facilitated along white fibers. This work uses normal brain atlases for extracting the proportions of white and gray matter and the diffusion tensors used for anisotropy. The paper also presents the results of applying this glioma model on real clinical datasets. [ABSTRACT FROM AUTHOR]

Applying diffusive models for simulating the spatiotemporal change of concentration of tumour cells is a modern application of predictive oncology. Diffusive models are used for modelling glioblastoma, the most aggressive type of glioma. This paper presents the results of applying a linear quadratic model for simulating the effects of radiotherapy on an advanced diffusive glioma model. This diffusive model takes into consideration the heterogeneous velocity of glioma in gray and white matter and the anisotropic migration of tumor cells, which is facilitated along white fibers. This work uses normal brain atlases for extracting the proportions of white and gray matter and the diffusion tensors used for anisotropy. The paper also presents the results of applying this glioma model on real clinical datasets. [ABSTRACT FROM AUTHOR]

Abstract: The early detection of breast cancer greatly improves prognosis. One of the earliest signs of cancer is the formation of clusters of microcalcifications. We introduce a novel method for microcalcification detection based on a biologically inspired adaptive model of contrast detection. This model is used in conjunction with image filtering based on anisotropic diffusion and curvilinear structure removal using local energy and phase congruency. An important practical issue in automatic detection methods is the selection of parameters: we show that the parameter values for our algorithm can be estimated automatically from the image. This way, the method is made robust and essentially free of parameter tuning. We report results on mammograms from two databases and show that the detection performance can be improved by first including a normalisation scheme. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We present an image analysis method that can detect and measure breast density from digitised mammograms. We present initial results on applying our method to characterise breast changes, in particular, changes due to Hormone Replacement Therapy (HRT). It has been established that long-term use of certain hormone replacement therapies can increase the risk of breast cancer, a fact that encourages the notion that objective measures of tissue density can be an important development in breast cancer image analysis. A set of 59 temporal pairs of mammograms of patients undergoing HRT (two images per patient) were used. The clinician’s assessment of density changes constituted the ground truth for evaluating the proposed quantitative measures of density change. The measures we developed are based on the Standard Mammogram Form (SMF) representation of interesting tissue and their performance (agreement with the expert’s description) is also compared to the “interactive thresholding” method that has been used in the past to characterise mammographic density. The results clearly indicate that present methods for measuring mammographic density fail to characterise temporal changes while the proposed measures have the potential to aid the radiologist in assessing temporal density changes both on a global and a local basis. [Copyright &y& Elsevier]

Increasing use is being made of Gd-DTPA contrast-enhanced magnetic resonance imaging for breast cancer assessment since it provides 3D functional information via pharmacokinetic interaction between contrast agent and tumour vascularity, and because it is applicable to women of all ages as well as patients with post-operative scarring. Contrast-enhanced MRI (CE-MRI) is complementary to conventional X-ray mammography, since it is a relatively low-resolution functional counterpart of a comparatively high-resolution 2D structural representation. However, despite the additional information provided by MRI, mammography is still an extremely important diagnostic imaging modality, particularly for several common conditions such as ductal carcinoma in situ (DCIS) where it has been shown that there is a strong correlation between microcalcification clusters and malignancy. Pathological indicators such as calcifications and fine spiculations are not visible in CE-MRI and therefore there is clinical and diagnostic value in fusing the high-resolution structural information available from mammography with the functional data acquired from MRI imaging. This paper presents a novel data fusion technique whereby medial–lateral oblique (MLO) and cranial–caudal (CC) mammograms (2D data) are registered to 3D contrast-enhanced MRI volumes. We utilise a combination of pharmacokinetic modelling, projection geometry, wavelet-based landmark detection and thin-plate spline non-rigid ‘warping’ to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. Of key importance is the use of a flexible wavelet-based feature extraction technique that enables feature correspondences to be robustly determined between the very different image characteristics of X-ray mammography and MRI. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples. [Copyright &y& Elsevier]

Artificial intelligence (AI) is revolutionizing the field of medical imaging, holding the potential to shift medicine from a reactive "sick-care" approach to a proactive focus on healthcare and prevention. The successful development of AI in this domain relies on access to large, comprehensive, and standardized real-world datasets that accurately represent diverse populations and diseases. However, images and data are sensitive, and as such, before using them in any way the data needs to be modified to protect the privacy of the patients. This paper explores the approaches in the domain of five EU projects working on the creation of ethically compliant and GDPR-regulated European medical imaging platforms, focused on cancer-related data. It presents the individual approaches to the de-identification of imaging data, and describes the problems and the solutions adopted in each case. Further, lessons learned are provided, enabling future projects to optimally handle the problem of data de-identification. Critical relevance statement: This paper presents key approaches from five flagship EU projects for the de-identification of imaging and clinical data offering valuable insights and guidelines in the domain. Key Points: ΑΙ models for health imaging require access to large amounts of data. Access to large imaging datasets requires an appropriate de-identification process. This paper provides de-identification guidelines from the AI for health imaging (AI4HI) projects. [ABSTRACT FROM AUTHOR]

Simple Summary: Deleterious LKB1 inactivation in KRAS-driven lung adenocarcinomas (LUACs) has been studied thoroughly; however, LKB1 inactivation is not limited in adenocarcinomatous histology, nor in KRAS mutational status. We investigated LKB1 loss by IHC in 188 metastatic and 60 non-metastatic tumors from patients with operable non-small cell lung cancer (NSCLC) of various histologies and its correlation with cell cycle targets, EMT inducers, antitumor immunity response regulators, cell adhesion molecules and KRAS co-mutations. LKB1 loss was associated with STING loss irrespective of KRAS status both overall and in lung adenocarcinomas (LUACs) and, importantly, also in the metastatic setting. Concurrent LKB1 loss and β-catenin loss of membranous expression correlated with a significant decrease in median overall survival and increased risk of death. The expression status of LKB1 in association with STING and β-catenin membranous expression status could be used as stratification factors for patients with operable NSCLC in the procedure of precision medicine in lung cancer. To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAFV600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16 downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low β-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumors yielding LKB1 loss and concomitant nonexistent or low β-catenin membrane expression experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71–6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and β-catenin in NSCLC, in prognosis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of two machine learning models in predicting the long-term complete pain resolution in patients undergoing ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT). Materials and methods: Within a 3-year period, 100 consecutive patients who underwent US-PICT for rotator cuff disease were prospectively enrolled. The location, maximum diameter, and type of each calcification were recorded. The degree of calcium retrieval was graded as complete or incomplete. Shoulder pain was assessed with the visual analogue scale (VAS) at baseline, 1-week, 1-month, and 1-year post-treatment. Measurements related to procedural details, patient, and calcification characteristics were used to construct a machine learning model for the prediction of pain at 1-year post-US-PICT. Two distinct models were built, one including VAS data at 1 week and another additionally including pain data at 1-month post-treatment. Variable importance analysis was performed for the 1-week model. Model performance was evaluated by using receiver operating characteristics (ROC) curves and the respective areas under the curve (AUC). Results: The model exhibited an AUC of 69.2% for the prediction of complete pain resolution at 1 year. The addition of VAS scores at 1 month did not significantly alter the performance of the algorithm. Age and baseline VAS scores were the most important variables for classification performance. Conclusion: The presented machine learning model exhibited an AUC of almost 70% in predicting complete pain resolution at 1 year. Pain data at 1 month do not appear to improve the performance of the algorithm. [ABSTRACT FROM AUTHOR]

Objectives: To develop a deep learning methodology that distinguishes early from late stages of avascular necrosis of the hip (AVN) to determine treatment decisions. Methods: Three convolutional neural networks (CNNs) VGG-16, Inception ResnetV2, InceptionV3 were trained with transfer learning (ImageNet) and finetuned with a retrospectively collected cohort of (n = 104) MRI examinations of AVN patients, to differentiate between early (ARCO 1–2) and late (ARCO 3–4) stages. A consensus CNN ensemble decision was recorded as the agreement of at least two CNNs. CNN and ensemble performance was benchmarked on an independent cohort of 49 patients from another country and was compared to the performance of two MSK radiologists. CNN performance was expressed with areas under the curve (AUC), the respective 95% confidence intervals (CIs) and precision, and recall and f1-scores. AUCs were compared with DeLong's test. Results: On internal testing, Inception-ResnetV2 achieved the highest individual performance with an AUC of 99.7% (95%CI 99–100%), followed by InceptionV3 and VGG-16 with AUCs of 99.3% (95%CI 98.4–100%) and 97.3% (95%CI 95.5–99.2%) respectively. The CNN ensemble the same AUCs Inception ResnetV2. On external validation, model performance dropped with VGG-16 achieving the highest individual AUC of 78.9% (95%CI 51.6–79.6%) The best external performance was achieved by the model ensemble with an AUC of 85.5% (95%CI 72.2–93.9%). No significant difference was found between the CNN ensemble and expert MSK radiologists (p = 0.22 and 0.092 respectively). Conclusion: An externally validated CNN ensemble accurately distinguishes between the early and late stages of AVN and has comparable performance to expert MSK radiologists. Clinical relevance statement: This paper introduces the use of deep learning for the differentiation between early and late avascular necrosis of the hip, assisting in a complex clinical decision that can determine the choice between conservative and surgical treatment. Key Points: • A convolutional neural network ensemble achieved excellent performance in distinguishing between early and late avascular necrosis. • The performance of the deep learning method was similar to the performance of expert readers. [ABSTRACT FROM AUTHOR]

Over the past decade rapid advancements in molecular imaging (MI) and artificial intelligence (AI) have revolutionized traditional musculoskeletal radiology. Molecular imaging refers to the ability of various methods to in vivo characterize and quantify biological processes, at a molecular level. The extracted information provides the tools to understand the pathophysiology of diseases and thus to early detect, to accurately evaluate the extend and to apply and evaluate targeted treatments. At present, molecular imaging mainly involves CT, MRI, radionuclide, US, and optical imaging and has been reported in many clinical and preclinical studies. Although originally MI techniques targeted at central nervous system disorders, later on their value on musculoskeletal disorders was also studied in depth. Meaningful exploitation of the large volume of imaging data generated by molecular and conventional imaging techniques, requires state-of-the-art computational methods that enable rapid handling of large volumes of information. AI allows end-to-end training of computer algorithms to perform tasks encountered in everyday clinical practice including diagnosis, disease severity classification and image optimization. Notably, the development of deep learning algorithms has offered novel methods that enable intelligent processing of large imaging datasets in an attempt to automate decision-making in a wide variety of settings related to musculoskeletal trauma. Current applications of AI include the diagnosis of bone and soft tissue injuries, monitoring of the healing process and prediction of injuries in the professional sports setting. This review presents the current applications of novel MI techniques and methods and the emerging role of AI regarding the diagnosis and evaluation of musculoskeletal trauma. [ABSTRACT FROM AUTHOR]

Magnetic Resonance (MR) images suffer from spatial inhomogeneity, known as bias field corruption. The N4ITK filter is a state-of-the-art method used for correcting the bias field to optimize MR-based quantification. In this study, a novel approach is presented to quantitatively evaluate the performance of N4 bias field correction for pelvic prostate imaging. An exploratory analysis, regarding the different values of convergence threshold, shrink factor, fitting level, number of iterations and use of mask, is performed to quantify the performance of N4 filter in pelvic MR images. The performance of a total of 240 different N4 configurations is examined using the Full Width at Half Maximum (FWHM) of the segmented periprostatic fat distribution as evaluation metric. Phantom T2weighted images were used to assess the performance of N4 for a uniform test tissue mimicking material, excluding factors such as patient related susceptibility and anatomy heterogeneity. Moreover, 89 and 204 T2weighted patient images from two public datasets acquired by scanners with a combined surface and endorectal coil at 1.5 T and a surface coil at 3 T, respectively, were utilized and corrected with a variable set of N4 parameters. Furthermore, two external public datasets were used to validate the performance of the N4 filter in T2weighted patient images acquired by various scanning conditions with different magnetic field strengths and coils. The results show that the set of N4 parameters, converging to optimal representations of fat in the image, were: convergence threshold 0.001, shrink factor 2, fitting level 6, number of iterations 100 and the use of default mask for prostate images acquired by a combined surface and endorectal coil at both 1.5 T and 3 T. The corresponding optimal N4 configuration for MR prostate images acquired by a surface coil at 1.5 T or 3 T was: convergence threshold 0.001, shrink factor 2, fitting level 5, number of iterations 25 and the use of default mask. Hence, periprostatic fat segmentation can be used to define the optimal settings for achieving T2weighted prostate images free from bias field corruption to provide robust input for further analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer therapy-related cardiac dysfunction (CTRCD) has been an urgent medical issue in patients that receive breast cancer therapies including anthracycline-based chemotherapies and/or targeted anti-HER2 therapies such as trastuzumab. Traditional biomarkers used as standard of care may be useful indicators of cardiac damage but their use to predict the onset of CTRCD lacks reliability. Ongoing clinical studies aim to explore new insights into the use of traditional biomarkers and investigate the promising role of novel biomarkers as reliable indicators and/or predictors of CTRCD. Patients with breast cancer could benefit from an alternative cardiac risk stratification plan that has the potential to predict the onset of CTRCD and/or detect CTRCD at early stages. The aim of this systematic review is to provide an overview of the human studies, which explore novel insights into traditional biomarkers and/or novel biomarkers that can be used for the early detection and/or prediction of CTRCD in breast cancer patients undergoing cardiotoxic-cancer therapies. Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD. [ABSTRACT FROM AUTHOR]

Identifying individual patient characteristics that contribute to long-term mental health deterioration following diagnosis of breast cancer (BC) is critical in clinical practice. The present study employed a supervised machine learning pipeline to address this issue in a subset of data from a prospective, multinational cohort of women diagnosed with stage I–III BC with a curative treatment intention. Patients were classified as displaying stable HADS scores (Stable Group; n = 328) or reporting a significant increase in symptomatology between BC diagnosis and 12 months later (Deteriorated Group; n = 50). Sociodemographic, life-style, psychosocial, and medical variables collected on the first visit to their oncologist and three months later served as potential predictors of patient risk stratification. The flexible and comprehensive machine learning (ML) pipeline used entailed feature selection, model training, validation and testing. Model-agnostic analyses aided interpretation of model results at the variable- and patient-level. The two groups were discriminated with a high degree of accuracy (Area Under the Curve = 0.864) and a fair balance of sensitivity (0.85) and specificity (0.87). Both psychological (negative affect, certain coping with cancer reactions, lack of sense of control/positive expectations, and difficulties in regulating negative emotions) and biological variables (baseline percentage of neutrophils, thrombocyte count) emerged as important predictors of mental health deterioration in the long run. Personalized break-down profiles revealed the relative impact of specific variables toward successful model predictions for each patient. Identifying key risk factors for mental health deterioration is an essential first step toward prevention. Supervised ML models may guide clinical recommendations toward successful illness adaptation. [ABSTRACT FROM AUTHOR]

Radiotranscriptomics is an emerging field that aims to investigate the relationships between the radiomic features extracted from medical images and gene expression profiles that contribute in the diagnosis, treatment planning, and prognosis of cancer. This study proposes a methodological framework for the investigation of these associations with application on non-small-cell lung cancer (NSCLC). Six publicly available NSCLC datasets with transcriptomics data were used to derive and validate a transcriptomic signature for its ability to differentiate between cancer and non-malignant lung tissue. A publicly available dataset of 24 NSCLC-diagnosed patients, with both transcriptomic and imaging data, was used for the joint radiotranscriptomic analysis. For each patient, 749 Computed Tomography (CT) radiomic features were extracted and the corresponding transcriptomics data were provided through DNA microarrays. The radiomic features were clustered using the iterative K-means algorithm resulting in 77 homogeneous clusters, represented by meta-radiomic features. The most significant differentially expressed genes (DEGs) were selected by performing Significance Analysis of Microarrays (SAM) and 2-fold change. The interactions among the CT imaging features and the selected DEGs were investigated using SAM and a Spearman rank correlation test with a False Discovery Rate (FDR) of 5%, leading to the extraction of 73 DEGs significantly correlated with radiomic features. These genes were used to produce predictive models of the meta-radiomics features, defined as p-metaomics features, by performing Lasso regression. Of the 77 meta-radiomic features, 51 can be modeled in terms of the transcriptomic signature. These significant radiotranscriptomics relationships form a reliable basis to biologically justify the radiomics features extracted from anatomic imaging modalities. Thus, the biological value of these radiomic features was justified via enrichment analysis on their transcriptomics-based regression models, revealing closely associated biological processes and pathways. Overall, the proposed methodological framework provides joint radiotranscriptomics markers and models to support the connection and complementarities between the transcriptome and the phenotype in cancer, as demonstrated in the case of NSCLC. [ABSTRACT FROM AUTHOR]

Automatic segmentation of the prostate of and the prostatic zones on MRI remains one of the most compelling research areas. While different image enhancement techniques are emerging as powerful tools for improving the performance of segmentation algorithms, their application still lacks consensus due to contrasting evidence regarding performance improvement and cross-model stability, further hampered by the inability to explain models' predictions. Particularly, for prostate segmentation, the effectiveness of image enhancement on different Convolutional Neural Networks (CNN) remains largely unexplored. The present work introduces a novel image enhancement method, named RACLAHE, to enhance the performance of CNN models for segmenting the prostate's gland and the prostatic zones. The improvement in performance and consistency across five CNN models (U-Net, U-Net++, U-Net3+, ResU-net and USE-NET) is compared against four popular image enhancement methods. Additionally, a methodology is proposed to explain, both quantitatively and qualitatively, the relation between saliency maps and ground truth probability maps. Overall, RACLAHE was the most consistent image enhancement algorithm in terms of performance improvement across CNN models with the mean increase in Dice Score ranging from 3 to 9% for the different prostatic regions, while achieving minimal inter-model variability. The integration of a feature driven methodology to explain the predictions after applying image enhancement methods, enables the development of a concrete, trustworthy automated pipeline for prostate segmentation on MR images. [ABSTRACT FROM AUTHOR]

Contemporary deep learning-based decision systems are well-known for requiring high-volume datasets in order to produce generalized, reliable, and high-performing models. However, the collection of such datasets is challenging, requiring time-consuming processes involving also expert clinicians with limited time. In addition, data collection often raises ethical and legal issues and depends on costly and invasive procedures. Deep generative models such as generative adversarial networks and variational autoencoders can capture the underlying distribution of the examined data, allowing them to create new and unique instances of samples. This study aims to shed light on generative data augmentation techniques and corresponding best practices. Through in-depth investigation, we underline the limitations and potential methodology pitfalls from critical standpoint and aim to promote open science research by identifying publicly available open-source repositories and datasets. [ABSTRACT FROM AUTHOR]

Stress conditions are manifested in different human body's physiological processes and the human face. Facial expressions are modelled consistently through the Facial Action Coding System (FACS) using the facial Action Units (AU) parameters. This paper focuses on the automated recognition and analysis of AUs in videos as quantitative indices to discriminate between neutral and stress states. A novel deep learning pipeline for automatic recognition of facial action units is proposed, relying on two publicly available annotated facial datasets for training, the UNBC and the BOSPHORUS datasets. Two types of descriptive facial features are extracted from the input images, geometric features (non-rigid 3D facial deformations due to facial expressions) and appearance features (deep facial appearance features). The extracted facial features are then fed to deep fully connected layers that regress AU intensities and robustly perform AU classification. The proposed algorithm is applied to the SRD'15 stress dataset, which contains neutral and stress states related to four types of stressors. We present thorough experimental results and comparisons, which indicate that the proposed methodology yields particularly promising performance in terms of both AU detection and stress recognition accuracy. Furthermore, the AUs relevant to stress were experimentally identified, providing evidence that their intensity is significantly increased during stress, which leads to a more expressive human face as compared to neutral states. [ABSTRACT FROM AUTHOR]

Differential diagnosis between avascular necrosis (AVN) and transient osteoporosis of the hip (TOH) can be complicated even for experienced MSK radiologists. Our study attempted to use MR images in order to develop a deep learning methodology with the use of transfer learning and a convolutional neural network (CNN) ensemble, for the accurate differentiation between the two diseases. An augmented dataset of 210 hips with TOH and 210 hips with AVN was used to finetune three ImageNet-trained CNNs (VGG-16, InceptionResNetV2, and InceptionV3). An ensemble decision was reached in a hard-voting manner by selecting the outcome voted by at least two of the CNNs. Inception-ResNet-V2 achieved the highest AUC (97.62%) similar to the model ensemble, followed by InceptionV3 (AUC of 96.82%) and VGG-16 (AUC 96.03%). Precision for the diagnosis of AVN and recall for the detection of TOH were higher in the model ensemble compared to Inception-ResNet-V2. Ensemble performance was significantly higher than that of an MSK radiologist and a fellow (P < 0.001). Deep learning was highly successful in distinguishing TOH from AVN, with a potential to aid treatment decisions and lead to the avoidance of unnecessary surgery. [ABSTRACT FROM AUTHOR]

Purpose: Subchondral insufficiency fractures (SIF) and advanced osteoarthritis (OA) of the knee are usually seen in conjunction with bone marrow lesions (BMLs) and their differentiation may pose a significant diagnostic challenge. We aimed to develop a convolutional neural network (CNN) ensemble which could successfully differentiate between these two entities.Materials and Methods: A total of 212 knees with SIF and 102 knees with advanced OA with BMLs were retrospectively included. Coronal fat suppressed PD-w images were augmented, resized and normalized, reaching a total of 1174 images. Data was used to fine-tune three ImageNet-pretrained CNNs (VGG-16, InceptionV3 and Inception-ResNet-V2). Agreement of at least two networks was recorded as the decision of the network ensemble. Ensemble performance was compared to that of two MSK radiologists on the validation set. Receiver operating characteristics (ROC) curves and the respective areas under the curve (AUC) were used to evaluate human and machine performance.Results: InceptionV3 achieved the highest AUC (93.68%) and VGG-16 the lowest AUC (82.18%) among individual CNNs. CNN ensemble achieved the highest overall performance with an AUC of 95.97%. The first of the two MSK radiologists achieved a performance similar to the ensemble, reaching an AUC of 91.95%. The second radiologist achieved lower AUC of 82.76% which was lower than both the other specialist and the ensemble (P < 0.001).Conclusion: A CNN ensemble was highly accurate in differentiating between SIF and OA, achieving a higher or equal performance to MSK radiologists. [ABSTRACT FROM AUTHOR]

The objective of this study is to assess standardized histograms of signal intensities of T2-weighted magnetic resonance image (MRI) modality before and after preoperative chemotherapy for nephroblastoma (Wilms' tumor). All analyzed patients are enrolled in the International Society of Paediatric Oncology (SIOP) 2001/GPOH trial.1 The question to be answered is whether the comparison of the histograms can add new knowledge by comparing them with the histology of the tumor after preoperative chemotherapy. Twenty-three unilateral nephroblastoma cases were analyzed. All patients were examined by MRI before and after preoperative chemotherapy treatment. T2 modalities of the MRIs were selected, and histogram changes were compared to histopathological data available after surgery. Of the 23 tumors, 22 decreased in volume following chemotherapy (median -57.99%; range 15.65 to -90.82%). The preliminary results suggest that standardized histograms of signal intensities of T2 MRI in nephroblastoma is not predicting histopathological diagnostic information and has no implications for the clinical assessment for further chemotherapy. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the possibility of predicting histological grade in patients with endometrial cancer on the basis of intravoxel incoherent motion (IVIM)-related histogram analysis parameters. This prospective study included 52 women with endometrial cancer (EC) who underwent MR imaging as initial staging in our hospital, allocated into low-grade (G1 and G2) and high-grade (G3) tumors according to the pathology reports. Regions of interest (ROIs) were drawn on the diffusion weighted images and apparent diffusion coefficient (ADC), true diffusivity (D), and perfusion fraction (f) using diffusion models were computed. Mean, median, skewness, kurtosis, and interquartile range (IQR) were calculated from the whole-tumor histogram. The IQR of the diffusion coefficient (D) was significantly lower in the low-grade tumors from that of the high-grade group with an adjusted p-value of less than 5% (0.048). The ROC curve analysis results of the statistically significant IQR of the D yielded an accuracy, sensitivity, and specificity of 74.5%, 70.1%, and 76.5% respectively, for discriminating low from high-grade tumors, with an optimal cutoff of 0.206 (×10−3 mm2/s) and an AUC of 75.4% (95% CI: 62.1 to 88.8). The IVIM modeling coupled with histogram analysis techniques is promising for preoperative differentiation between low- and high-grade EC tumors. [ABSTRACT FROM AUTHOR]

Interference, in wireless networks, is a central phenomenon when multiple uncoordinated links share a common communication medium. The study of the interference channel was initiated by Shannon in 1961 and since then this problem has been thoroughly elaborated at the Information theoretic level but its characterization still remains an open issue. When multiple uncoordinated links share a common medium the effect of interference is a crucial limiting factor for network performance. In this work, using cross layer cooperative communication techniques, we study how to compensate interference in the context of wireless biomedical networks, where many links transferring biomedical or other health related data may be formed and suffer from all other interfering transmissions, to allow successful receptions and improve the overall network performance. We define the interference limited communication range to be the critical communication region around a receiver, with a number of surrounding interfering nodes, within which a successful communication link can be formed. Our results indicate that we can achieve more successful transmissions by adapting the transmission rate and power, to the path loss exponent, and the selected mode of the underline communication technique allowing interference mitigation and when possible lower power consumption and increase achievable transmission rates. [ABSTRACT FROM AUTHOR]

Interference, in wireless networks, is a central phenomenon when multiple uncoordinated links share a common communication medium. The study of the interference channel was initiated by Shannon in 1961 and since then this problem has been thoroughly elaborated at the Information theoretic level but its characterization still remains an open issue. When multiple uncoordinated links share a common medium the effect of interference is a crucial limiting factor for network performance. In this work, using cross layer cooperative communication techniques, we study how to compensate interference in the context of wireless biomedical networks, where many links transferring biomedical or other health related data may be formed and suffer from all other interfering transmissions, to allow successful receptions and improve the overall network performance. We define the interference limited communication range to be the critical communication region around a receiver, with a number of surrounding interfering nodes, within which a successful communication link can be formed. Our results indicate that we can achieve more successful transmissions by adapting the transmission rate and power, to the path loss exponent, and the selected mode of the underline communication technique allowing interference mitigation and when possible lower power consumption and increase achievable transmission rates. [ABSTRACT FROM AUTHOR]

Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of rare neoplasms with increasing incidence over the last decades. Localization of GEP-NETs and their metastases is a vital component for the implementation of accurate and patient-tailored treatment strategies. Addressing this challenge requires the employment of multidisciplinary imaging approaches, with hybrid positron emission tomography/computed tomography (PET/CT) imaging techniques standing at the forefront of this effort. GEP-NETs exhibit several pathophysiologic characteristics, which can serve as highly specific molecular targets that can be effectively visualized and quantified by means of PET-radiopharmaceuticals, facilitating diagnosis, accurate staging and efficient monitoring of treatment response. Furthermore, the capability for whole-body, in-vivo, non-invasive characterization of the molecular heterogeneity of the disease, provides strong prognostic information, while enabling the selection of patients suitable for precision-based theranostic approaches. The dual tracer (18F-FDG & 68Ga-DOTA-peptides) PET/CT imaging approach is the current optimal diagnostic imaging strategy, since it enables tumor localization, accurate staging, non-invasive whole-body total tumor burden characterization of disease heterogeneity, while providing strong prognostic information and guidance towards treatment strategy. Moreover, 64Cu-DOTATATE has been recently approved by FDA for SSTRs positive NETs, promising substantial diagnostic and logistical benefits. Furthermore, 18F-DOPA offers diagnostic capabilities for serotonin-secreting GEP-NETs which are not characterized by cell-surface over-expression of somatostatin receptors (SSTRs) and cannot be seen on morphological imaging. In addition, PET/CT with agents targeting the expression of glucagon-like peptide-1 receptor (GLP-R1) should be considered in cases of clinical suspicion for insulinomas that cannot be detected by morphological imaging or STTRs PET/CT imaging. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) constitutes the third most commonly diagnosed cancer in males and the second in females. Precise histopathological classification of CRC tissue pathology is the cornerstone not only for diagnosis but also for patients' management decision making. An automated system able to accurately classify different CRC tissue regions may increase diagnostic precision and alleviate clinical workload. However, tissue classification is a challenging task due to the variability in morphological and textural characteristics present in histopathology images. In this study, an artificial neural network was trained to classify between eight classes of CRC tissue image patches derived from a public dataset with 5000 CRC histopathology image tiles. A total of 532 multi-level pathomics features examined at different scales were extracted by visual descriptors such as local binary patterns, wavelet transforms and Gabor filters. An exhaustive evaluation involving a variety of wavelet families and parameters was performed in order to shed light on the impact of scale on pathomics based CRC tissue differentiation. Our model achieved a performance accuracy of 95.3% with tenfold cross validation demonstrating superior performance compared to 87.4% reported in recent studies. Furthermore, we experimentally showed that the first and the second levels of the wavelet approximations can be used without compromising classification performance. [ABSTRACT FROM AUTHOR]

COVID-19 has led to an unprecedented healthcare crisis with millions of infected people across the globe often pushing infrastructures, healthcare workers and entire economies beyond their limits. The scarcity of testing kits, even in developed countries, has led to extensive research efforts towards alternative solutions with high sensitivity. Chest radiological imaging paired with artificial intelligence (AI) can offer significant advantages in diagnosis of novel coronavirus infected patients. To this end, transfer learning techniques are used for overcoming the limitations emanating from the lack of relevant big datasets, enabling specialized models to converge on limited data, as in the case of X-rays of COVID-19 patients. In this study, we present an interpretable AI framework assessed by expert radiologists on the basis on how well the attention maps focus on the diagnostically-relevant image regions. The proposed transfer learning methodology achieves an overall area under the curve of 1 for a binary classification problem across a 5-fold training/testing dataset. [ABSTRACT FROM AUTHOR]

PURPOSE: Capitalizing on the promise of patient-reported outcomes (PROs), electronic implementations of PROs (ePROs) are expected to play an important role in the development of novel digital health interventions targeting palliative cancer care. We performed a systematic and mapping review of the scientific literature on the current ePRO-based approaches used for palliative cancer care. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines, the conducted review answered the research questions: "What are the current ePRO-based approaches for palliative cancer care; what is their contribution/value in the domain of palliative cancer care; and what are the potential gaps, challenges, and opportunities for further research?" After a screening step, the corpus of included articles indexed in PubMed or the Web of Science underwent full text review, which mapped the articles across 15 predefined axes. RESULTS: The corpus of 24 mapped studies includes 9 study protocols, 7 technical tools/solutions, 7 pilot/feasibility/acceptability studies, and 1 evaluation study. The review of the corpus revealed (1) an archetype of ePRO-enabled interventions for palliative cancer care, which most commonly use ePROs as study end point assessment instruments rather than integral intervention components; (2) the fact that the literature has not fully embraced the modern definitions that expand the scope of palliative care; (3) the striking shortage of promising ubiquitous computing devices (eg, smart activity trackers); and (4) emerging evidence about the benefits of narrowing down the target cancer population, especially when combined with modern patient-centered intervention design methodologies. CONCLUSION: Although research on exploiting ePROs for the development of digital palliative cancer care interventions is considerably active and demonstrates several successful cases, there is considerable room for improvement along the directions of the aforementioned findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Accumulating evidence during the last decades revealed that androgens exert membrane-initiated actions leading to the modulation of significant cellular processes, important for cancer cell growth and metastasis (including prostate and breast), that involve signaling via specific kinases. Collectively, many nonclassical, cell surface-initiated androgen actions are mediated by novel membrane androgen receptors (mARs), unrelated to nuclear androgen receptors. Recently, our group identified the G protein coupled oxo-eicosanoid receptor 1 (OXER1) (a receptor of the arachidonic acid metabolite, 5-oxoeicosatetraenoic acid, 5-oxoETE) as a novel mAR involved in the rapid effects of androgens. However, two other membrane proteins, G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) have also been portrayed as mARs, related to the extranuclear action of androgens. In the present work, we present a comparative study of in silico pharmacology, gene expression and immunocytochemical data of the three receptors in various prostate and breast cancer cell lines. Furthermore, we analyzed the immunohistochemical expression of these receptors in human tumor and non-tumoral specimens and provide a pattern of expression and intracellular distribution. [ABSTRACT FROM AUTHOR]

In the last decade, clinicians have started to shift from an individualistic perspective of the patient towards family-centred models of care, due to the increasing evidence from research and clinical practice of the crucial role of significant others in determining the patient's adjustment to cancer disease and management. eHealth tools can be considered a means to compensate the services gap and support outpatient care flows. Within the works of the European H2020 iManageCancer project, a review of the literature in the field of family resilience was conducted, in order to determine how to monitor the patient and his/her family's resilience through an eHealth platform. An analysis of existing family resilience questionnaires suggested that no measure was appropriate for cancer patients and their families. For this reason, a new family resilience questionnaire (named FaRe) was developed to screen the patient's and caregiver's psycho-emotional resources. Composed of 24 items, it is divided into four subscales: Communication and Cohesion, Perceived Family Coping, Religiousness and Spirituality, and Perceived Social Support. Embedded in the iManageCancer eHealth platform, it allows users and clinicians to monitor the patient's and the caregivers' resilience throughout the cancer trajectory. [ABSTRACT FROM AUTHOR]

Nowadays, patients have a wealth of information available on the Internet. Despite the potential benefits of Internet health information seeking, several concerns have been raised about the quality of information and about the patient's capability to evaluate medical information and to relate it to their own disease and treatment. As such, novel tools are required to effectively guide patients and provide high-quality medical information in an intelligent and personalised manner. With this aim, this paper presents the Personal Health Information Recommender (PHIR), a system to empower patients by enabling them to search in a high-quality document repository selected by experts, avoiding the information overload of the Internet. In addition, the information provided to the patients is personalised, based on individual preferences, medical conditions and other profiling information. Despite the generality of our approach, we apply the PHIR to a personal health record system constructed for cancer patients and we report on the design, the implementation and a preliminary validation of the platform. To the best of our knowledge, our platform is the only one combining natural language processing, ontologies and personal information to offer a unique user experience. [ABSTRACT FROM AUTHOR]

Clinical decision support systems can play a crucial role in healthcare delivery as they promise to improve health outcomes and patient safety, reduce medical errors and costs and contribute to patient satisfaction. Used in an optimal way, they increase the quality of healthcare by proposing the right information and intervention to the right person at the right time in the healthcare delivery process. This paper reports on a specific approach to integrated clinical decision support and patient guidance in the cancer domain as proposed by the H2020 iManageCancer project. This project aims at facilitating efficient self-management and management of cancer according to the latest available clinical knowledge and the local healthcare delivery model, supporting patients and their healthcare providers in making informed decisions on treatment choices and in managing the side effects of their therapy. The iManageCancer platform is a comprehensive platform of interconnected mobile tools to empower cancer patients and to support them in the management of their disease in collaboration with their doctors. The backbone of the iManageCancer platform comprises a personal health record and the central decision support unit (CDSU). The latter offers dedicated services to the end users in combination with the apps iManageMy-Health and iSupportMyPatients. The CDSU itself is composed of the so-called Care Flow Engine (CFE) and the model repository framework (MRF). The CFE executes personalised and workflow oriented formal disease management diagrams (Care Flows). In decision points of such a Care Flow, rules that operate on actual health information of the patient decide on the treatment path that the system follows. Alternatively, the system can also invoke a predictive model of the MRF to proceed with the best treatment path in the diagram. Care Flow diagrams are designed by clinical experts with a specific graphical tool that also deploys these diagrams as executable workflows in the CFE following the Business Process Model and Notation (BPMN) standard. They are exposed as services that patients or their doctors can use in their apps in order to manage certain aspects of the cancer disease like pain, fatigue or the monitoring of chemotherapies at home. The mHealth platform for cancer patients is currently being assessed in clinical pilots in Italy and Germany and in several end-user workshops. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: 10.1007/s10044-021-01012-9 [ABSTRACT FROM AUTHOR]

Purpose: Biomedical research is being catalyzed by the vast amount of data rapidly collected through the application of information technologies (IT). Despite IT advances, the methods for involving patients and citizens in biomedical research remain static, paper-based and organized around national boundaries and anachronistic legal frameworks. The purpose of this paper is to study the current practices for obtaining consent for biobanking and the legal requirements for reusing the available biomaterial and data in EU and finally to present a novel tool to this direction enabling the secondary use of data and biomaterial.Method: We review existing European legislation for secondary use of patient's biomaterial and data for research, identify types and scopes of consent, formal requirements for consent, and consider their implications for implementing electronic consent tools. To this direction, we proceed further to develop a modular tool, named Donor's Support Tool (DST), designed to connect researchers with participants, and to promote engagement, informed participation and individual decision making.Results: To identify the advantages of our solution we compare our tool with six other relevant approaches. The results show that our tool scores higher than the other tools in functionality, security and intelligence whereas it is the only one free and open-source. In addition, the potential of our solution is shown by a proof of concept deployment in an existing clinical setting, where it was really appreciated, as streamlining the relevant workflow. [ABSTRACT FROM AUTHOR]

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 () 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. [ABSTRACT FROM AUTHOR]

Although the idea of the personalization of patient care dates back to the time of Hippocrates, recent advances in diagnostic medical imaging and molecular medicine are gradually transforming healthcare services, by offering information and diagnostic tools enabling individualized patient management. Facilitating personalized / precision medicine requires taking into account multiple heterogenous parameters, such as sociodemographics, gene variability, environmental and lifestyle factors. Therefore, one of the most critical challenges in personalized medicine is the need to transform large, multi-modal data into decision support tools, capable of bridging the translational gap to the clinical setting. Towards these challenges, deep learning (DL) provides a novel approach, which enables obtaining or developing high-accuracy, multi-modal predictive models, that allow the implementation of the personalized medicine vision in the near future. DL is a highly effective strategy in addressing these challenges, with DL-based models leading to unprecedented results, matching or even improving state-of-the-art prediction/detection rates based on both intuitive and non-intuitive disease descriptors. These results hold promise for significant socio-economic benefits from the application of DL personalized medicine. [ABSTRACT FROM AUTHOR]

Background: A plethora of publicly available biomedical resources do currently exist and are constantly increasing at a fast rate. In parallel, specialized repositories are been developed, indexing numerous clinical and biomedical tools. The main drawback of such repositories is the difficulty in locating appropriate resources for a clinical or biomedical decision task, especially for non-Information Technology expert users. In parallel, although NLP research in the clinical domain has been active since the 1960s, progress in the development of NLP applications has been slow and lags behind progress in the general NLP domain. The aim of the present study is to investigate the use of semantics for biomedical resources annotation with domain specific ontologies and exploit Natural Language Processing methods in empowering the non-Information Technology expert users to efficiently search for biomedical resources using natural language.Methods: A Natural Language Processing engine which can "translate" free text into targeted queries, automatically transforming a clinical research question into a request description that contains only terms of ontologies, has been implemented. The implementation is based on information extraction techniques for text in natural language, guided by integrated ontologies. Furthermore, knowledge from robust text mining methods has been incorporated to map descriptions into suitable domain ontologies in order to ensure that the biomedical resources descriptions are domain oriented and enhance the accuracy of services discovery. The framework is freely available as a web application at ( http://calchas.ics.forth.gr/ ).Results: For our experiments, a range of clinical questions were established based on descriptions of clinical trials from the ClinicalTrials.gov registry as well as recommendations from clinicians. Domain experts manually identified the available tools in a tools repository which are suitable for addressing the clinical questions at hand, either individually or as a set of tools forming a computational pipeline. The results were compared with those obtained from an automated discovery of candidate biomedical tools. For the evaluation of the results, precision and recall measurements were used. Our results indicate that the proposed framework has a high precision and low recall, implying that the system returns essentially more relevant results than irrelevant.Conclusions: There are adequate biomedical ontologies already available, sufficiency of existing NLP tools and quality of biomedical annotation systems for the implementation of a biomedical resources discovery framework, based on the semantic annotation of resources and the use on NLP techniques. The results of the present study demonstrate the clinical utility of the application of the proposed framework which aims to bridge the gap between clinical question in natural language and efficient dynamic biomedical resources discovery. [ABSTRACT FROM AUTHOR]

Aim: We present a computerized system for the assessment of the long-term risk of developing diabetesrelated complications. Methods: The core of the system consists of a set of predictive models, developed through a data-mining/machine-learning approach, which are able to evaluate individual patient profiles and provide personalized risk assessments. Missing data is a common issue in (electronic) patient records, thus themodels are paired with a module for the intelligent management of missing information. Results: The system has been deployed and made publicly available as Web service, and it has been fully integrated within the diabetes-management platform developed by the European project REACTION. Preliminary usability tests showed that the clinicians judged the models useful for risk assessment and for communicating the risk to the patient. Furthermore, the system performs as well as the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine when both systems are tested on an independent cohort of UK diabetes patients. Conclusions: Our work provides a working example of risk-stratification tool that is (a) specific for diabetes patients, (b) able to handle several different diabetes related complications, (c) performing as well as the widely known UKPDS Risk Engine on an external validation cohort. [ABSTRACT FROM AUTHOR]

Personal health record (PHR) systems are a rapidly expanding area in the field of health information technology which motivates an ongoing research towards their evaluation in several different aspects. In this direction, we present a systematic review of the currently available PHR systems. Initially, we define a clear and concise set of requirements for efficient PHR systems which is based on real-world implementation experiences of several European research projects and also on established and widely used formal standards. Subsequently, these requirements are used to perform a systematic evaluation of existing PHR system implementations. Our evaluation study provides a thorough requirement analysis and an insight on the current status of personal health record systems. The results of the present work can therefore be used as a basis for future evaluation studies which should be conducted periodically as technology evolves and requirements are revised. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme is the most aggressive type of glioma and the most common malignant primary intra-axial brain tumor. In an effort to predict the evolution of the disease and optimize therapeutical decisions, several models have been proposed for simulating the growth pattern of glioma. One of the latest models incorporates cell proliferation and invasion, angiogenic net rates, oxygen consumption, and vasculature. These factors, particularly oxygenation levels, are considered fundamental factors of tumor heterogeneity and compartmentalization. This paper focuses on the initialization of the cancer cell populations and vasculature based on imaging examinations of the patient and presents a feasibility study on vasculature prediction over time. To this end, pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging using Toft's model are used in order tofeed the model. Ktrans is used as a metric of the density of endothelial cells (vasculature); at the same time, it also helps to discriminate distinct image areas of interest, under a set of assumptions. Feasibility results of applying the model to a real clinical case are presented, including a study on the effect of certain parameters on the pattern of the simulated tumor. [ABSTRACT FROM AUTHOR]

This study aimed to investigate which of the two frequently adopted perfusion models better describes the contrast enhanced ultrasound (CEUS) perfusion signal in order to produce meaningful imaging markers with the goal of developing a machine-learning model that can classify perfusion curves as benign or malignant in breast cancer data. Twenty-five patients with high suspicion of breast cancer were analyzed with exponentially modified Gaussian (EMG) and gamma variate functions (GVF). The adjusted R2 metric was the criterion for assessing model performance. Various classifiers were trained on the quantified perfusion curves in order to classify the curves as benign or malignant on a voxel basis. Sensitivity, specificity, geometric mean, and AUROC were the validation metrics. The best quantification model was EMG with an adjusted R2 of 0.60 ± 0.26 compared to 0.56 ± 0.25 for GVF. Logistic regression was the classifier with the highest performance (sensitivity, specificity, Gmean, and AUROC = 89.2 ± 10.7, 70.0 ± 18.5, 77.1 ± 8.6, and 91.0 ± 6.6, respectively). This classification method obtained similar results that are consistent with the current literature. Breast cancer patients can benefit from early detection and characterization prior to biopsy. [ABSTRACT FROM AUTHOR]

In an epoch where shared decision making is gaining importance, a patient's commitment to and knowledge about his/her health condition is becoming more and more relevant. Health literacy is one of the most important factors in enhancing the involvement of patients in their care. Nevertheless, other factors can impair patient processing and understanding of health information: psychological aspects and cognitive style may affect the way patients approach, select, and retain information. This paper describes the development and validation of a short and easy to fill-out questionnaire that measures and collects psycho-cognitive information about patients, named ALGA-C. ALGA-C is a multilingual, multidevice instrument, and its validation was carried out in healthy people and breast cancer patients. In addition to the aforementioned questionnaire, a patient profiling mechanism has also been developed. The ALGA-C Profiler enables physicians to rapidly inspect each patient's individual cognitive profile and see at a glance the areas of concern. With this tool, doctors can modulate the language, vocabulary, and content of subsequent discussions with the patient, thus enabling easier understanding by the patient. This, in turn, helps the patient formulate questions and participate on an equal footing in the decision-making processes. Finally, a preview is given on the techniques under consideration for exploiting the constructed patient profile by a personal health record (PHR). Predefined rules will use a patient's profile to personalise the contents of the information presented and to customise ways in which users complete their tasks in a PHR system. This optimises information delivery to patients and makes it easier for the patient to decide what is of interest to him/her at the moment. [ABSTRACT FROM AUTHOR]

Radiogenomic and radiotranscriptomic studies have the potential to pave the way for a holistic decision support system built on genomics, transcriptomics, radiomics, deep features and clinical parameters to assess treatment evaluation and care planning. The integration of invasive and routine imaging data into a common feature space has the potential to yield robust models for inferring the drivers of underlying biological mechanisms. In this non-small cell lung carcinoma study, a multi-omics representation comprised deep features and transcriptomics was evaluated to further explore the synergetic and complementary properties of these diverse multi-view data sources by utilizing data-driven machine learning models. The proposed deep radiotranscriptomic analysis is a feature-based fusion that significantly enhances sensitivity by up to 0.174 and AUC by up to 0.22, compared to the baseline single source models, across all experiments on the unseen testing set. Additionally, a radiomics-based fusion was also explored as an alternative methodology yielding radiomic signatures that are comparable to several previous publications in the field of radiogenomics. Furthermore, the machine learning multi-omics analysis based on deep features and transcriptomics achieved an AUC performance of up to 0.831 ± 0.09/0.925 ± 0.04 for the examined molecular and histology subtypes analysis, respectively. The clinical impact of such high-performing models can add prognostic value and lead to optimal treatment assessment by targeting specific oncogenes, namely the response of tyrosine kinase inhibitors of EGFR mutated or predicting the chemotherapy resistance of KRAS mutated tumors. [ABSTRACT FROM AUTHOR]