X-rays radiomics-based machine learning classification of atypical cartilaginous tumour and high-grade chondrosarcoma of long bones.

BACKGROUND: Atypical cartilaginous tumour (ACT) and high-grade chondrosarcoma (CS) of long bones are respectively managed with active surveillance or curettage and wide resection. Our aim was to determine diagnostic performance of X-rays radiomics-based machine learning for classification of ACT and high-grade CS of long bones. METHODS: This retrospective, IRB-approved study included 150 patients with surgically treated and histology-proven lesions at two tertiary bone sarcoma centres. At centre 1, the dataset was split into training (n = 71 ACT, n = 24 high-grade CS) and internal test (n = 19 ACT, n = 6 high-grade CS) cohorts, respectively, based on the date of surgery. At centre 2, the dataset constituted the external test cohort (n = 12 ACT, n = 18 high-grade CS). Manual segmentation was performed on frontal view X-rays, using MRI or CT for preliminary identification of lesion margins. After image pre-processing, radiomic features were extracted. Dimensionality reduction included stability, coefficient of variation, and mutual information analyses. In the training cohort, after class balancing, a machine learning classifier (Support Vector Machine) was automatically tuned using nested 10-fold cross-validation. Then, it was tested on both the test cohorts and compared to two musculoskeletal radiologists' performance using McNemar's test. FINDINGS: Five radiomic features (3 morphology, 2 texture) passed dimensionality reduction. After tuning on the training cohort (AUC = 0.75), the classifier had 80%, 83%, 79% and 80%, 89%, 67% accuracy, sensitivity, and specificity in the internal (temporally independent) and external (geographically independent) test cohorts, respectively, with no difference compared to the radiologists (p ≥ 0.617). INTERPRETATION: X-rays radiomics-based machine learning accurately differentiates between ACT and high-grade CS of long bones. FUNDING: AIRC Investigator Grant.

Unveiling the Diagnostic Potential of Linguistic Markers in Identifying Individuals with Parkinson's Disease through Artificial Intelligence: A Systematic Review.

While extensive research has documented the cognitive changes associated with Parkinson's disease (PD), a relatively small portion of the empirical literature investigated the language abilities of individuals with PD. Recently, artificial intelligence applied to linguistic data has shown promising results in predicting the clinical diagnosis of neurodegenerative disorders, but a deeper investigation of the current literature available on PD is lacking. This systematic review investigates the nature of language disorders in PD by assessing the contribution of machine learning (ML) to the classification of patients with PD. A total of 10 studies published between 2016 and 2023 were included in this review. Tasks used to elicit language were mainly structured or unstructured narrative discourse. Transcriptions were mostly analyzed using Natural Language Processing (NLP) techniques. The classification accuracy (%) ranged from 43 to 94, sensitivity (%) ranged from 8 to 95, specificity (%) ranged from 3 to 100, AUC (%) ranged from 32 to 97. The most frequent optimal linguistic measures were lexico-semantic (40%), followed by NLP-extracted features (26%) and morphological consistency features (20%). Artificial intelligence applied to linguistic markers provides valuable insights into PD. However, analyzing measures derived from narrative discourse can be time-consuming, and utilizing ML requires specialized expertise. Moving forward, it is important to focus on facilitating the integration of both narrative discourse analysis and artificial intelligence into clinical practice.

Computational analysis of five neurodegenerative diseases reveals shared and specific genetic loci.

Neurodegenerative diseases (ND) are heterogeneous disorders of the central nervous system that share a chronic and selective process of neuronal cell death. A computational approach to investigate shared genetic and specific loci was applied to 5 different ND: Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), and Lewy body dementia (LBD). The datasets were analyzed separately, and then we compared the obtained results. For this purpose, we applied a genetic correlation analysis to genome-wide association datasets and revealed different genetic correlations with several human traits and diseases. In addition, a clumping analysis was carried out to identify SNPs genetically associated with each disease. We found 27 SNPs in AD, 6 SNPs in ALS, 10 SNPs in PD, 17 SNPs in MS, and 3 SNPs in LBD. Most of them are located in non-coding regions, with the exception of 5 SNPs on which a protein structure and stability prediction was performed to verify their impact on disease. Furthermore, an analysis of the differentially expressed miRNAs of the 5 examined pathologies was performed to reveal regulatory mechanisms that could involve genes associated with selected SNPs. In conclusion, the results obtained constitute an important step toward the discovery of diagnostic biomarkers and a better understanding of the diseases.

Using Radiomics and Machine Learning Applied to MRI to Predict Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer.

Neoadjuvant chemotherapy plus radical surgery could be a safe alternative to chemo-radiation in cervical cancer patients who are not willing to receive radiotherapy. The response to neoadjuvant chemotherapy is the main factor influencing the need for adjunctive treatments and survival. In the present paper we aim to develop a machine learning model based on cervix magnetic resonance imaging (MRI) images to stratify the single-subject risk of cervical cancer. We collected MRI images from 72 subjects. Among these subjects, 28 patients (38.9%) belonged to the "Not completely responding" class and 44 patients (61.1%) belonged to the 'Completely responding' class according to their response to treatment. This image set was used for the training and cross-validation of different machine learning models. A robust radiomic approach was applied, under the hypothesis that the radiomic features could be able to capture the disease heterogeneity among the two groups. Three models consisting of three ensembles of machine learning classifiers (random forests, support vector machines, and k-nearest neighbor classifiers) were developed for the binary classification task of interest ("Not completely responding" vs. "Completely responding"), based on supervised learning, using response to treatment as the reference standard. The best model showed an ROC-AUC (%) of 83 (majority vote), 82.3 (mean) [79.9-84.6], an accuracy (%) of 74, 74.1 [72.1-76.1], a sensitivity (%) of 71, 73.8 [68.7-78.9], and a specificity (%) of 75, 74.2 [71-77.5]. In conclusion, our preliminary data support the adoption of a radiomic-based approach to predict the response to neoadjuvant chemotherapy.

A Radiomic-Based Machine Learning System to Diagnose Age-Related Macular Degeneration from Ultra-Widefield Fundus Retinography.

The present study was conducted to investigate the potential of radiomics to develop an explainable AI-based system to be applied to ultra-widefield fundus retinographies (UWF-FRTs) with the objective of predicting the presence of the early signs of Age-related Macular Degeneration (AMD) and stratifying subjects with low- versus high-risk of AMD. The ultimate aim was to provide clinicians with an automatic classifier and a signature of objective quantitative image biomarkers of AMD. The use of Machine Learning (ML) and radiomics was based on intensity and texture analysis in the macular region, detected by a Deep Learning (DL)-based macular detector. Two-hundred and twenty six UWF-FRTs were retrospectively collected from two centres and manually annotated to train and test the algorithms. Notably, the combination of the ML-based radiomics model and the DL-based macular detector reported 93% sensitivity and 74% specificity when applied to the data of the centre used for external testing, capturing explainable features associated with drusen or pigmentary abnormalities. In comparison to the human operator's annotations, the system yielded a 0.79 Cohen κ, demonstrating substantial concordance. To our knowledge, these results are the first provided by a radiomic approach for AMD supporting the suitability of an explainable feature extraction method combined with ML for UWF-FRT.

From genetic correlations of Alzheimer's disease to classification with artificial neural network models.

Sporadic Alzheimer's disease (AD) is a complex neurological disorder characterized by many risk loci with potential associations with different traits and diseases. AD, characterized by a progressive loss of neuronal functions, manifests with different symptoms such as decline in memory, movement, coordination, and speech. The mechanisms underlying the onset of AD are not always fully understood, but involve a multiplicity of factors. Early diagnosis of AD plays a central role as it can offer the possibility of early treatment, which can slow disease progression. Currently, the methods of diagnosis are cognitive testing, neuroimaging, or cerebrospinal fluid analysis that can be time-consuming, expensive, invasive, and not always accurate. In the present study, we performed a genetic correlation analysis using genome-wide association statistics from a large study of AD and UK Biobank, to examine the association of AD with other human traits and disorders. In addition, since hippocampus, a part of cerebral cortex could play a central role in several traits that are associated with AD; we analyzed the gene expression profiles of hippocampus of AD patients applying 4 different artificial neural network models. We found 65 traits correlated with AD grouped into 9 clusters: medical conditions, fluid intelligence, education, anthropometric measures, employment status, activity, diet, lifestyle, and sexuality. The comparison of different 4 neural network models along with feature selection methods on 5 Alzheimer's gene expression datasets showed that the simple basic neural network model obtains a better performance (66% of accuracy) than other more complex methods with dropout and weight regularization of the network.

MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor of the extremities.

PURPOSE: To determine diagnostic performance of MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor (ALT) of the extremities. MATERIAL AND METHODS: This retrospective study was performed at three tertiary sarcoma centers and included 150 patients with surgically treated and histology-proven lesions. The training-validation cohort consisted of 114 patients from centers 1 and 2 (n = 64 lipoma, n = 50 ALT). The external test cohort consisted of 36 patients from center 3 (n = 24 lipoma, n = 12 ALT). 3D segmentation was manually performed on T1- and T2-weighted MRI. After extraction and selection of radiomic features, three machine learning classifiers were trained and validated using nested fivefold cross-validation. The best-performing classifier according to previous analysis was evaluated and compared to an experienced musculoskeletal radiologist in the external test cohort. RESULTS: Eight features passed feature selection and were incorporated into the machine learning models. After training and validation (74% ROC-AUC), the best-performing classifier (Random Forest) showed 92% sensitivity and 33% specificity in the external test cohort with no statistical difference compared to the radiologist (p = 0.474). CONCLUSION: MRI radiomics-based machine learning may classify deep-seated lipoma and ALT of the extremities with high sensitivity and negative predictive value, thus potentially serving as a non-invasive screening tool to reduce unnecessary referral to tertiary tumor centers.

Impact of the Extremities Positioning on the Set-Up Reproducibility for the Total Marrow Irradiation Treatment.

Total marrow (lymph node) irradiation (TMI/TMLI) delivery requires more time than standard radiotherapy treatments. The patient's extremities, through the joints, can experience large movements. The reproducibility of TMI/TMLI patients' extremities was evaluated to find the best positioning and reduce unwanted movements. Eighty TMI/TMLI patients were selected (2013-2022). During treatment, a cone-beam computed tomography (CBCT) was performed for each isocenter to reposition the patient. CBCT-CT pairs were evaluated considering: (i) online vector shift (OVS) that matched the two series; (ii) residual vector shift (RVS) to reposition the patient's extremities; (iii) qualitative agreement (range 1-5). Patients were subdivided into (i) arms either leaning on the frame or above the body; (ii) with or without a personal cushion for foot positioning. The Mann-Whitney test was considered (p < 0.05 significant). Six-hundred-twenty-nine CBCTs were analyzed. The median OVS was 4.0 mm, with only 1.6% of cases ranked < 3, and 24% of RVS > 10 mm. Arms leaning on the frame had significantly smaller RVS than above the body (median: 8.0 mm/6.0 mm, p < 0.05). Using a personal cushion for the feet significantly improved the RVS than without cushions (median: 8.5 mm/1.8 mm, p < 0.01). The role and experience of the radiotherapy team are fundamental to optimizing the TMI/TMLI patient setup.

Evaluation of plan complexity and dosimetric plan quality of total marrow and lymphoid irradiation using volumetric modulated arc therapy.

PURPOSE: To assess the impact of the planner's experience and optimization algorithm on the plan quality and complexity of total marrow and lymphoid irradiation (TMLI) delivered by means of volumetric modulated arc therapy (VMAT) over 2010-2022 at our institute. METHODS: Eighty-two consecutive TMLI plans were considered. Three complexity indices were computed to characterize the plans in terms of leaf gap size, irregularity of beam apertures, and modulation complexity. Dosimetric points of the target volume (D2%) and organs at risk (OAR) (Dmean) were automatically extracted to combine them with plan complexity and obtain a global quality score (GQS). The analysis was stratified based on the different optimization algorithms used over the years, including a knowledge-based (KB) model. Patient-specific quality assurance (QA) using Portal Dosimetry was performed retrospectively, and the gamma agreement index (GAI) was investigated in conjunction with plan complexity. RESULTS: Plan complexity significantly reduced over the years (r = -0.50, p < 0.01). Significant differences in plan complexity and plan dosimetric quality among the different algorithms were observed. Moreover, the KB model allowed to achieve significantly better dosimetric results to the OARs. The plan quality remained similar or even improved during the years and when moving to a newer algorithm, with GQS increasing from 0.019 ± 0.002 to 0.025 ± 0.003 (p < 0.01). The significant correlation between GQS and time (r = 0.33, p = 0.01) indicated that the planner's experience was relevant to improve the plan quality of TMLI plans. Significant correlations between the GAI and the complexity metrics (r = -0.71, p < 0.01) were also found. CONCLUSION: Both the planner's experience and algorithm version are crucial to achieve an optimal plan quality in TMLI plans. Thus, the impact of the optimization algorithm should be carefully evaluated when a new algorithm is introduced and in system upgrades. Knowledge-based strategies can be useful to increase standardization and improve plan quality of TMLI treatments.

MRI-based artificial intelligence to predict infection following total hip arthroplasty failure.

PURPOSE: To investigate whether artificial intelligence (AI) can differentiate septic from non-septic total hip arthroplasty (THA) failure based on preoperative MRI features. MATERIALS AND METHODS: We included 173 patients (98 females, age: 67 ± 12 years) subjected to first-time THA revision surgery after preoperative pelvis MRI. We divided the patients into a training/validation/internal testing cohort (n = 117) and a temporally independent external-testing cohort (n = 56). MRI features were used to train, validate and test a machine learning algorithm based on support vector machine (SVM) to predict THA infection on the training-internal validation cohort with a nested fivefold validation approach. Machine learning performance was evaluated on independent data from the external-testing cohort. RESULTS: MRI features were significantly more frequently observed in THA infection (P < 0.001), except bone destruction, periarticular soft-tissue mass, and fibrous membrane (P > 0.005). Considering all MRI features in the training/validation/internal-testing cohort, SVM classifier reached 92% sensitivity, 62% specificity, 79% PPV, 83% NPV, 82% accuracy, and 81% AUC in predicting THA infection, with bone edema, extracapsular edema, and synovitis having been the best predictors. After being tested on the external-testing cohort, the classifier showed 92% sensitivity, 79% specificity, 89% PPV, 83% NPV, 88% accuracy, and 89% AUC in predicting THA infection. SVM classifier showed 81% sensitivity, 76% specificity, 66% PPV, 88% NPV, 80% accuracy, and 74% AUC in predicting THA infection in the training/validation/internal-testing cohort based on the only presence of periprosthetic bone marrow edema on MRI, while it showed 68% sensitivity, 89% specificity, 93% PPV, 60% NPV, 75% accuracy, and 79% AUC in the external-testing cohort. CONCLUSION: AI using SVM classifier showed promising results in predicting THA infection based on MRI features. This model might support radiologists in identifying THA infection.

Artificial intelligence (AI) in biomedical research: discussion on authors' declaration of AI in their articles title.

Artificial intelligence (AI) and its different approaches, from machine learning to deep learning, are not new. We discuss here about the declaration of AI in the title of those articles dealing with AI. From 1990 to 2021, while AI articles in the PubMed increased from 300 to 59,596, the percentage declaring AI in the title describes a U-like-shaped curve: about 30% in early 1990s, less than 13% in 2005-2014, again 30% in 2020-2021. A similar trend was observed for AI in medical imaging. While the initial decline could be due to the establishment of AI methods, the recent increase could be related to the capacity of AI to outperform humans, especially in image recognition, fuelled by the adoption of graphic processing units for general purpose computing. The recent increase may also be due to the relevance of open issues about AI, including the standardisation of methods, explainability of results, and concerns about AI-induced epoch-making transformations: to say "We are using AI" in the title may also reflect these concerns.

Automatic planning of the lower extremities for total marrow irradiation using volumetric modulated arc therapy.

PURPOSE: Total marrow (and lymphoid) irradiation (TMI-TMLI) is limited by the couch travel range of modern linacs, which forces the treatment delivery to be split into two plans with opposite orientations: a head-first supine upper-body plan, and a feet-first supine lower extremities plan. A specific field junction is thus needed to obtain adequate target coverage in the overlap region of the two plans. In this study, an automatic procedure was developed for field junction creation and lower extremities plan optimization. METHODS: Ten patients treated with TMI-TMLI at our institution were selected retrospectively. The planning of the lower extremities was performed automatically. Target volume parameters (CTV_J­V98% > 98%) at the junction region and several dose statistics (D98%, Dmean, and D2%) were compared between automatic and manual plans. The modulation complexity score (MCS) was used to assess plan complexity. RESULTS: The automatic procedure required 60-90 min, depending on the case. All automatic plans achieved clinically acceptable dosimetric results (CTV_J­V98% > 98%), with significant differences found at the junction region, where Dmean and D2% increased on average by 2.4% (p < 0.03) and 3.0% (p < 0.02), respectively. Similar plan complexity was observed (median MCS = 0.12). Since March 2022, the automatic procedure has been introduced in our clinic, reducing the TMI-TMLI simulation-to-delivery schedule by 2 days. CONCLUSION: The developed procedure allowed treatment planning of TMI-TMLI to be streamlined, increasing efficiency and standardization, preventing human errors, while maintaining the dosimetric plan quality and complexity of manual plans. Automated strategies can simplify the future adoption and clinical implementation of TMI-TMLI treatments in new centers.

Radiomics and Molecular Classification in Endometrial Cancer (The ROME Study): A Step Forward to a Simplified Precision Medicine.

Molecular/genomic profiling is the most accurate method to assess prognosis of endometrial cancer patients. Radiomic profiling allows for the extraction of mineable high-dimensional data from clinical radiological images, thus providing noteworthy information regarding tumor tissues. Interestingly, the adoption of radiomics shows important results for screening, diagnosis and prognosis, across various radiological systems and oncologic specialties. The central hypothesis of the prospective trial is that combining radiomic features with molecular features might allow for the identification of various classes of risks for endometrial cancer, e.g., predicting unfavorable molecular/genomic profiling. The rationale for the proposed research is that once validated, radiomics applied to ultrasonographic images would be an effective, innovative and inexpensive method for tailoring operative and postoperative treatment modalities in endometrial cancer. Patients with newly diagnosed endometrial cancer will have ultrasonographic evaluation and radiomic analysis of the ultrasonographic images. We will correlate radiomic features with molecular/genomic profiling to classify prognosis.

Determinants of Self-Perceived Health: The Importance of Physical Well-Being but Also of Mental Health and Cognitive Functioning.

With life expectancy increasing for the general population, public health promotion activities should be a priority to aim at a reduction of the burden and costs of hospitalization, disability, and lifelong treatment. This study aimed to explore the influence of parameters pertaining to different aspects of well-being, including physical and mental health and cognitive functioning, on self-perceived health, a predictor of chronic disease prevalence and mortality. We used data from the Survey of Health, Aging and Retirement in Europe (SHARE) project gathered between 2013 and 2017, obtaining a sample of 96,902 participants (63.23 ± 6.77 years). We found a strong association between the self-perceived health rating and not only physical health aspects but also mental health and cognitive functioning. In particular, BMI, chronic diseases and medications, muscle strength, and mobility issues had a strong effect on self-perceived health, as also did the quality of life, depression, and verbal fluency, while other aspects, such as individual characteristics, limitations in daily activities, and pain, among others only had a small effect. These results show that public health and prevention interventions should prioritize the targeting of all aspects of well-being and not only of physical health, acknowledging self-perceived health rating as a simple tool that could help provide a complete overview of psycho-physical well-being and functional status.

Consequences of exposure to pollutants on respiratory health: From genetic correlations to causal relationships.

Modern society grew rapidly over the last few decades and this led to an alarming increase in air pollutants and a worsening of the human health, especially in relation to the respiratory system. Indeed, chronic respiratory diseases were the third main cause of death in 2017, with over 3 million of deaths. Furthermore, the pollution has considerable consequences both for burden medical expenses and environmental. However, the mechanisms linking pollutants to the onset of these diseases remain unclear. Thus, in this study we addressed this problem through the United Kingdom BioBank database, analyzing 170 genome-wide association studies (103 related to respiratory diseases and 67 related to pollutants). We analyzed the genetic correlations and causal relationships of these traits, leveraging the summary statistics and bioinformatics packages such as Linkage Disequilibrium Score Regression and Latent Causal Variable. We obtained 158 significant genetic correlations and subsequently we analyzed them through the Latent Causal Variable analysis, obtaining 20 significant causal relationships. The most significant were between "Workplace full of chemicals or other fumes: Sometimes" and "Condition that has ever been diagnosed by a doctor: Asthma" and between "Workplace very dusty: Sometimes" and "Condition that has ever been diagnosed by a doctor: Emphysema or chronic bronchitis". Finally, we identified single nucleotide polymorphisms independently associated with sveral pollutants to analyze the genes and pathways that could be involved in the onset of the aforementioned respiratory system disorders and that could be useful clinical target. This study highlighted how crucial are the air condition of the working environments and the type of transport used in the onset of respiratory-related morbidity. Based on that, we also suggested some interventions, in order to improve quality life and develop new and eco-friendly society and life style, such as improving indoor air circulation, the use of public transport and urban reforestation.

Applications of artificial intelligence in stereotactic body radiation therapy.

This topical review focuses on the applications of artificial intelligence (AI) tools to stereotactic body radiation therapy (SBRT). The high dose per fraction and the limited number of fractions in SBRT require stricter accuracy than standard radiation therapy. The intent of this review is to describe the development and evaluate the possible benefit of AI tools integration into the radiation oncology workflow for SBRT automation. The selected papers were subdivided into four sections, representative of the whole radiotherapy process: 'AI in SBRT target and organs at risk contouring', 'AI in SBRT planning', 'AI during the SBRT delivery', and 'AI for outcome prediction after SBRT'. Each section summarises the challenges, as well as limits and needs for improvement to achieve better integration of AI tools in the clinical workflow.

Development and Validation of an AI-driven Mammographic Breast Density Classification Tool Based on Radiologist Consensus.

Mammographic breast density (BD) is commonly visually assessed using the Breast Imaging Reporting and Data System (BI-RADS) four-category scale. To overcome inter- and intraobserver variability of visual assessment, the authors retrospectively developed and externally validated a software for BD classification based on convolutional neural networks from mammograms obtained between 2017 and 2020. The tool was trained using the majority BD category determined by seven board-certified radiologists who independently visually assessed 760 mediolateral oblique (MLO) images in 380 women (mean age, 57 years ± 6 [SD]) from center 1; this process mimicked training from a consensus of several human readers. External validation of the model was performed by the three radiologists whose BD assessment was closest to the majority (consensus) of the initial seven on a dataset of 384 MLO images in 197 women (mean age, 56 years ± 13) obtained from center 2. The model achieved an accuracy of 89.3% in distinguishing BI-RADS a or b (nondense breasts) versus c or d (dense breasts) categories, with an agreement of 90.4% (178 of 197 mammograms) and a reliability of 0.807 (Cohen κ) compared with the mode of the three readers. This study demonstrates accuracy and reliability of a fully automated software for BD classification. Keywords: Mammography, Breast, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms Supplemental material is available for this article. © RSNA, 2022.

A tri-modal tissue-equivalent anthropomorphic phantom for PET, CT and multi-parametric MRI radiomics.

PURPOSE: Radiomics has emerged as an advanced image processing methodology to define quantitative imaging biomarkers for prognosis and prediction of treatment response and outcome. The development of quantitative imaging biomarkers requires careful analysis to define their accuracy, stability and reproducibility through phantom measurements. Few efforts were devoted to develop realistic anthropomorphic phantoms. In this work, we developed a multimodality image phantom suitable for PET, CT and multiparametric MRI imaging. METHODS: A tissue-equivalent gel-based mixture was designed and tested for compatibility with different imaging modalities. Calibration measurements allowed to assess gel composition to simulate PET, CT and MRI contrasts of oncological lesions. The characterized gel mixture was used to create realistic synthetic lesions (e.g. lesions with irregular shape and non-uniform image contrast), to be inserted in a standard anthropomorphic phantom. In order to show phantom usefulness, issues related to accuracy, stability and reproducibility of radiomic biomarkers were addressed as proofs-of-concept. RESULTS: The procedure for gel preparation was straightforward and the characterized gel mixture allowed to mime simultaneously oncological lesion contrast in CT, PET and MRI imaging. Proofs-of-concept studies suggested that phantom measurements can be customized for specific clinical situations and radiomic protocols. CONCLUSIONS: We developed a strategy to manufacture an anthropomorphic, tissue-equivalent, multimodal phantom to be customized on specific radiomics protocols, for addressing specific methodological issues both in mono and multicentric studies.

Identification of key miRNAs in prostate cancer progression based on miRNA-mRNA network construction.

Prostate cancer (PC) is one of the major male cancers. Differential diagnosis of PC is indispensable for the individual therapy, i.e., Gleason score (GS) that describes the grade of cancer can be used to choose the appropriate therapy. However, the current techniques for PC diagnosis and prognosis are not always effective. To identify potential markers that could be used for differential diagnosis of PC, we analyzed miRNA-mRNA interactions and we build specific networks for PC onset and progression. Key differentially expressed miRNAs for each GS were selected by calculating three parameters of network topology measures: the number of their single regulated mRNAs (NSR), the number of target genes (NTG) and NSR/NTG. miRNAs that obtained a high statistically significant value of these three parameters were chosen as potential biomarkers for computational validation and pathway analysis. 20 miRNAs were identified as key candidates for PC. 8 out of 20 miRNAs (miR-25-3p, miR-93-3p, miR-122-5p, miR-183-5p, miR-615-3p, miR-7-5p, miR-375, and miR-92a-3p) were differentially expressed in all GS and proposed as biomarkers for PC onset. In addition, "Extracellular-receptor interaction", "Focal adhesion", and "microRNAs in cancer" were significantly enriched by the differentially expressed target genes of the identified miRNAs. miR-10a-5p was found to be differentially expressed in GS 6, 7, and 8 in PC samples. 3 miRNAs were identified as PC GS-specific differentially expressed miRNAs: miR-155-5p was identified in PC samples with GS 6, and miR-142-3p and miR-296-3p in PC samples with GS 9. The efficacy of 20 miRNAs as potential biomarkers was revealed with a Random Forest classification using an independent dataset. The results demonstrated our 20 miRNAs achieved a better performance (AUC: 0.73) than miRNAs selected with Boruta algorithm (AUC: 0.55), a method for the automated feature extraction. Studying miRNA-mRNA associations, key miRNAs were identified with a computational approach for PC onset and progression. Further experimental validations are needed for future translational development.