Deep pathomics: A new image-based tool for predicting response to treatment in stage III non-small cell lung cancer.

Despite the advantages offered by personalized treatments, there is presently no way to predict response to chemoradiotherapy in patients with non-small cell lung cancer (NSCLC). In this exploratory study, we investigated the application of deep learning techniques to histological tissue slides (deep pathomics), with the aim of predicting the response to therapy in stage III NSCLC. We evaluated 35 digitalized tissue slides (biopsies or surgical specimens) obtained from patients with stage IIIA or IIIB NSCLC. Patients were classified as responders (12/35, 34.7%) or non-responders (23/35, 65.7%) based on the target volume reduction shown on weekly CT scans performed during chemoradiation treatment. Digital tissue slides were tested by five pre-trained convolutional neural networks (CNNs)-AlexNet, VGG, MobileNet, GoogLeNet, and ResNet-using a leave-two patient-out cross validation approach, and we evaluated the networks' performances. GoogLeNet was globally found to be the best CNN, correctly classifying 8/12 responders and 10/11 non-responders. Moreover, Deep-Pathomics was found to be highly specific (TNr: 90.1) and quite sensitive (TPr: 0.75). Our data showed that AI could surpass the capabilities of all presently available diagnostic systems, supplying additional information beyond that currently obtainable in clinical practice. The ability to predict a patient's response to treatment could guide the development of new and more effective therapeutic AI-based approaches and could therefore be considered an effective and innovative step forward in personalised medicine.

Radiomic Machine-Learning Analysis of Multiparametric Magnetic Resonance Imaging in the Diagnosis of Clinically Significant Prostate Cancer: New Combination of Textural and Clinical Features.

BACKGROUND: The aim of our study was to develop a radiomic tool for the prediction of clinically significant prostate cancer. METHODS: From September 2020 to December 2021, 91 patients who underwent magnetic resonance imaging prostate fusion biopsy at our institution were selected. Prostate cancer aggressiveness was assessed by combining the three orthogonal planes-Llocal binary pattern the 3Dgray level co-occurrence matrix, and other first order statistical features with clinical (semantic) features. The 487 features were used to predict whether the Gleason score was clinically significant (≥7) in the final pathology. A feature selection algorithm was used to determine the most predictive features, and at the end of the process, nine features were chosen through a 10-fold cross validation. RESULTS: The feature analysis revealed a detection accuracy of 83.5%, with a clinically significant precision of 84.4% and a clinically significant sensitivity of 91.5%. The resulting area under the curve was 80.4%. CONCLUSIONS: Radiomic analysis allowed us to develop a tool that was able to predict a Gleason score of ≥7. This new tool may improve the detection rate of clinically significant prostate cancer and overcome the limitations of the subjective interpretation of magnetic resonance imaging, reducing the number of useless biopsies.

MRI- and Histologic-Molecular-Based Radio-Genomics Nomogram for Preoperative Assessment of Risk Classes in Endometrial Cancer.

High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by "ProMisE". This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.

A Multimodal Ensemble Driven by Multiobjective Optimisation to Predict Overall Survival in Non-Small-Cell Lung Cancer.

Lung cancer accounts for more deaths worldwide than any other cancer disease. In order to provide patients with the most effective treatment for these aggressive tumours, multimodal learning is emerging as a new and promising field of research that aims to extract complementary information from the data of different modalities for prognostic and predictive purposes. This knowledge could be used to optimise current treatments and maximise their effectiveness. To predict overall survival, in this work, we investigate the use of multimodal learning on the CLARO dataset, which includes CT images and clinical data collected from a cohort of non-small-cell lung cancer patients. Our method allows the identification of the optimal set of classifiers to be included in the ensemble in a late fusion approach. Specifically, after training unimodal models on each modality, it selects the best ensemble by solving a multiobjective optimisation problem that maximises both the recognition performance and the diversity of the predictions. In the ensemble, the labels of each sample are assigned using the majority voting rule. As further validation, we show that the proposed ensemble outperforms the models learning a single modality, obtaining state-of-the-art results on the task at hand.

CNN-Based Approaches with Different Tumor Bounding Options for Lymph Node Status Prediction in Breast DCE-MRI.

BACKGROUND: The axillary lymph node status (ALNS) is one of the most important prognostic factors in breast cancer (BC) patients, and it is currently evaluated by invasive procedures. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), highlights the physiological and morphological characteristics of primary tumor tissue. Deep learning approaches (DL), such as convolutional neural networks (CNNs), are able to autonomously learn the set of features directly from images for a specific task. MATERIALS AND METHODS: A total of 155 malignant BC lesions evaluated via DCE-MRI were included in the study. For each patient's clinical data, the tumor histological and MRI characteristics and axillary lymph node status (ALNS) were assessed. LNS was considered to be the final label and dichotomized (LN+ (27 patients) vs. LN- (128 patients)). Based on the concept that peritumoral tissue contains valuable information about tumor aggressiveness, in this work, we analyze the contributions of six different tumor bounding options to predict the LNS using a CNN. These bounding boxes include a single fixed-size box (SFB), a single variable-size box (SVB), a single isotropic-size box (SIB), a single lesion variable-size box (SLVB), a single lesion isotropic-size box (SLIB), and a two-dimensional slice (2DS) option. According to the characteristics of the volumes considered as inputs, three different CNNs were investigated: the SFB-NET (for the SFB), the VB-NET (for the SVB, SIB, SLVB, and SLIB), and the 2DS-NET (for the 2DS). All the experiments were run in 10-fold cross-validation. The performance of each CNN was evaluated in terms of accuracy, sensitivity, specificity, the area under the ROC curve (AUC), and Cohen's kappa coefficient (K). RESULTS: The best accuracy and AUC are obtained by the 2DS-NET (78.63% and 77.86%, respectively). The 2DS-NET also showed the highest specificity, whilst the highest sensibility was attained by the VB-NET based on the SVB and SIB as bounding options. CONCLUSION: We have demonstrated that a selective inclusion of the DCE-MRI's peritumoral tissue increases accuracy in the lymph node status prediction in BC patients using CNNs as a DL approach.

Quantib Prostate Compared to an Expert Radiologist for the Diagnosis of Prostate Cancer on mpMRI: A Single-Center Preliminary Study.

Background: To evaluate the clinical utility of an Artificial Intelligence (AI) radiology solution, Quantib Prostate, for prostate cancer (PCa) lesions detection on multiparametric Magnetic Resonance Images (mpMRI). Methods: Prostate mpMRI exams of 108 patients were retrospectively studied. The diagnostic performance of an expert radiologist (>8 years of experience) and of an inexperienced radiologist aided by Quantib software were compared. Three groups of patients were assessed: patients with positive mpMRI, positive target biopsy, and/or at least one positive random biopsy (group A, 73 patients); patients with positive mpMRI and a negative biopsy (group B, 14 patients), and patients with negative mpMRI who did not undergo biopsy (group-C, 21 patients). Results: In group A, the AI-assisted radiologist found new lesions with positive biopsy correlation, increasing the diagnostic PCa performance when compared with the expert radiologist, reaching an SE of 92.3% and a PPV of 90.1% (vs. 71.7% and 84.4%). In group A, the expert radiologist found 96 lesions on 73 mpMRI exams (17.7% PIRADS3, 56.3% PIRADS4, and 26% PIRADS5). The AI-assisted radiologist found 121 lesions (0.8% PIRADS3, 53.7% PIRADS4, and 45.5% PIRADS5). At biopsy, 33.9% of the lesions were ISUP1, 31.4% were ISUP2, 22% were ISUP3, 10.2% were ISUP4, and 2.5% were ISUP5. In group B, where biopsies were negative, the AI-assisted radiologist excluded three lesions but confirmed all the others. In group-C, the AI-assisted radiologist found 37 new lesions, most of them PIRADS 3, with 32.4% localized in the peripherical zone and 67.6% in the transition zone. Conclusions: Quantib software is a very sensitive tool to use specifically in high-risk patients (high PIRADS and high Gleason score).

A Case of Secretory Carcinoma in a Patient With a History of Contralateral Medullary Carcinoma.

Background: Secretory and medullary carcinomas of the breast are rare subtypes of infiltrating ductal carcinoma. The different histological behavior of medullary and secretory carcinomas is correlated with different imaging features on mammography, ultrasound, and magnetic resonance imaging. Case Report: We report the case of a Caucasian woman in which both subtypes of tumors were diagnosed in an 8-year time interval and evaluate, in antithesis, histopathological and imaging aspects of medullary and secretory carcinoma. Conclusion: To our knowledge, this is the first case reported in literature of secretory carcinoma with a complete imaging tumor evaluation in a patient with a previous contralateral medullary cancer.

Pareto optimization of deep networks for COVID-19 diagnosis from chest X-rays.

The year 2020 was characterized by the COVID-19 pandemic that has caused, by the end of March 2021, more than 2.5 million deaths worldwide. Since the beginning, besides the laboratory test, used as the gold standard, many applications have been applying deep learning algorithms to chest X-ray images to recognize COVID-19 infected patients. In this context, we found out that convolutional neural networks perform well on a single dataset but struggle to generalize to other data sources. To overcome this limitation, we propose a late fusion approach where we combine the outputs of several state-of-the-art CNNs, introducing a novel method that allows us to construct an optimum ensemble determining which and how many base learners should be aggregated. This choice is driven by a two-objective function that maximizes, on a validation set, the accuracy and the diversity of the ensemble itself. A wide set of experiments on several publicly available datasets, accounting for more than 92,000 images, shows that the proposed approach provides average recognition rates up to 93.54% when tested on external datasets.

3T-MRI Artificial Intelligence in Patients with Invasive Breast Cancer to Predict Distant Metastasis Status: A Pilot Study.

BACKGROUND: The incidence of breast cancer metastasis has decreased over the years. However, 20-30% of patients with early breast cancer still die from metastases. The purpose of this study is to evaluate the performance of a Deep Learning Convolutional Neural Networks (CNN) model to predict the risk of distant metastasis using 3T-MRI DCE sequences (Dynamic Contrast-Enhanced). METHODS: A total of 157 breast cancer patients who underwent staging 3T-MRI examinations from January 2011 to July 2022 were retrospectively examined. Patient data, tumor histological and MRI characteristics, and clinical and imaging follow-up examinations of up to 7 years were collected. Of the 157 MRI examinations, 39/157 patients (40 lesions) had distant metastases, while 118/157 patients (120 lesions) were negative for distant metastases (control group). We analyzed the role of the Deep Learning technique using a single variable size bounding box (SVB) option and employed a Voxel Based (VB) NET CNN model. The CNN performance was evaluated in terms of accuracy, sensitivity, specificity, and area under the ROC curve (AUC). RESULTS: The VB-NET model obtained a sensitivity, specificity, accuracy, and AUC of 52.50%, 80.51%, 73.42%, and 68.56%, respectively. A significant correlation was found between the risk of distant metastasis and tumor size, and the expression of PgR and HER2. CONCLUSIONS: We demonstrated a currently insufficient ability of the Deep Learning approach in predicting a distant metastasis status in patients with BC using CNNs.

AIforCOVID: Predicting the clinical outcomes in patients with COVID-19 applying AI to chest-X-rays. An Italian multicentre study.

Recent epidemiological data report that worldwide more than 53 million people have been infected by SARS-CoV-2, resulting in 1.3 million deaths. The disease has been spreading very rapidly and few months after the identification of the first infected, shortage of hospital resources quickly became a problem. In this work we investigate whether artificial intelligence working with chest X-ray (CXR) scans and clinical data can be used as a possible tool for the early identification of patients at risk of severe outcome, like intensive care or death. Indeed, further to induce lower radiation dose than computed tomography (CT), CXR is a simpler and faster radiological technique, being also more widespread. In this respect, we present three approaches that use features extracted from CXR images, either handcrafted or automatically learnt by convolutional neuronal networks, which are then integrated with the clinical data. As a further contribution, this work introduces a repository that collects data from 820 patients enrolled in six Italian hospitals in spring 2020 during the first COVID-19 emergency. The dataset includes CXR images, several clinical attributes and clinical outcomes. Exhaustive evaluation shows promising performance both in 10-fold and leave-one-centre-out cross-validation, suggesting that clinical data and images have the potential to provide useful information for the management of patients and hospital resources.

Deep Reinforcement Learning for Fractionated Radiotherapy in Non-Small Cell Lung Carcinoma.

Lung cancer is by far the leading cause of cancer death among both men and women. Radiation therapy is one of the main approaches to lung cancer treatment, and its planning is crucial for the therapy outcome. However, the current practice that uniformly delivers the dose does not take into account the patient-specific tumour features that may affect treatment success. Since radiation therapy is by its very nature a sequential procedure, Deep Reinforcement Learning (DRL) is a well-suited methodology to overcome this limitation. In this respect, in this work we present a DRL controller optimizing the daily dose fraction delivered to the patient on the basis of CT scans collected over time during the therapy, offering a personalized treatment not only for volume adaptation, as currently intended, but also for daily fractionation. Furthermore, this contribution introduces a virtual radiotherapy environment based on a set of ordinary differential equations modelling the tissue radiosensitivity by combining both the effect of the radiotherapy treatment and cell growth. Their parameters are estimated from CT scans routinely collected using the Particle Swarm Optimization algorithm. This permits the DRL to learn the optimal behaviour through an iterative trial and error process with the environment. We performed several experiments considering three rewards functions modelling treatment strategies with different tissue aggressiveness and two exploration strategies for the exploration-exploitation dilemma. The results show that our DRL approach can adapt to radiation therapy treatment, optimizing its behaviour according to the different reward functions and outperforming the current clinical practice.

The Impact of Tumor Edema on T2-Weighted 3T-MRI Invasive Breast Cancer Histological Characterization: A Pilot Radiomics Study.

BACKGROUND: to evaluate the contribution of edema associated with histological features to the prediction of breast cancer (BC) prognosis using T2-weighted MRI radiomics. METHODS: 160 patients who underwent staging 3T-MRI from January 2015 to January 2019, with 164 histologically proven invasive BC lesions, were retrospectively reviewed. Patient data (age, menopausal status, family history, hormone therapy), tumor MRI-features (location, margins, enhancement) and histological features (histological type, grading, ER, PgR, HER2, Ki-67 index) were collected. Of the 160 MRI exams, 120 were considered eligible, corresponding to 127 lesions. T2-MRI were used to identify edema, which was classified in four groups: peritumoral, pre-pectoral, subcutaneous, or diffuse. A semi-automatic segmentation of the edema was performed for each lesion, using 3D Slicer open-source software. Main radiomics features were extracted and selected using a wrapper selection method. A Random Forest type classifier was trained to measure the performance of predicting histological factors using semantic features (patient data and MRI features) alone and semantic features associated with edema radiomics features. RESULTS: edema was absent in 37 lesions and present in 127 (62 peritumoral, 26 pre-pectoral, 16 subcutaneous, 23 diffuse). The AUC-classifier obtained by associating edema radiomics with semantic features was always higher compared to the AUC-classifier obtained from semantic features alone, for all five histological classes prediction (0.645 vs. 0.520 for histological type, 0.789 vs. 0.590 for grading, 0.487 vs. 0.466 for ER, 0.659 vs. 0.546 for PgR, and 0.62 vs. 0.573 for Ki67). CONCLUSIONS: radiomic features extracted from tumor edema contribute significantly to predicting tumor histology, increasing the accuracy obtained from the combination of patient clinical characteristics and breast imaging data.

3T MRI-Radiomic Approach to Predict for Lymph Node Status in Breast Cancer Patients.

BACKGROUND: axillary lymph node (LN) status is one of the main breast cancer prognostic factors and it is currently defined by invasive procedures. The aim of this study is to predict LN metastasis combining MRI radiomics features with primary breast tumor histological features and patients' clinical data. METHODS: 99 lesions on pre-treatment contrasted 3T-MRI (DCE). All patients had a histologically proven invasive breast cancer and defined LN status. Patients' clinical data and tumor histological analysis were previously collected. For each tumor lesion, a semi-automatic segmentation was performed, using the second phase of DCE-MRI. Each segmentation was optimized using a convex-hull algorithm. In addition to the 14 semantics features and a feature ROI volume/convex-hull volume, 242 other quantitative features were extracted. A wrapper selection method selected the 15 most prognostic features (14 quantitative, 1 semantic), used to train the final learning model. The classifier used was the Random Forest. RESULTS: the AUC-classifier was 0.856 (label = positive or negative). The contribution of each feature group was lower performance than the full signature. CONCLUSIONS: the combination of patient clinical, histological and radiomics features of primary breast cancer can accurately predict LN status in a non-invasive way.

Visual4DTracker: a tool to interact with 3D + t image stacks.

BACKGROUND: Biological phenomena usually evolves over time and recent advances in high-throughput microscopy have made possible to collect multiple 3D images over time, generating [Formula: see text] (or 4D) datasets. To extract useful information there is the need to extract spatial and temporal data on the particles that are in the images, but particle tracking and feature extraction need some kind of assistance. RESULTS: This manuscript introduces our new freely downloadable toolbox, the Visual4DTracker. It is a MATLAB package implementing several useful functionalities to navigate, analyse and proof-read the track of each particle detected in any [Formula: see text] stack. Furthermore, it allows users to proof-read and to evaluate the traces with respect to a given gold standard. The Visual4DTracker toolbox permits the users to visualize and save all the generated results through a user-friendly graphical user interface. This tool has been successfully used in three applicative examples. The first processes synthetic data to show all the software functionalities. The second shows how to process a 4D image stack showing the time-lapse growth of Drosophila cells in an embryo. The third example presents the quantitative analysis of insulin granules in living beta-cells, showing that such particles have two main dynamics that coexist inside the cells. CONCLUSIONS: Visual4DTracker is a software package for MATLAB to visualize, handle and manually track [Formula: see text] stacks of microscopy images containing objects such cells, granules, etc.. With its unique set of functions, it remarkably permits the user to analyze and proof-read 4D data in a friendly 3D fashion. The tool is freely available at https://drive.google.com/drive/folders/19AEn0TqP-2B8Z10kOavEAopTUxsKUV73?usp=sharing.

A radiomic approach for adaptive radiotherapy in non-small cell lung cancer patients.

The primary goal of precision medicine is to minimize side effects and optimize efficacy of treatments. Recent advances in medical imaging technology allow the use of more advanced image analysis methods beyond simple measurements of tumor size or radiotracer uptake metrics. The extraction of quantitative features from medical images to characterize tumor pathology or heterogeneity is an interesting process to investigate, in order to provide information that may be useful to guide the therapies and predict survival. This paper discusses the rationale supporting the concept of radiomics and the feasibility of its application to Non-Small Cell Lung Cancer in the field of radiation oncology research. We studied 91 stage III patients treated with concurrent chemoradiation and adaptive approach in case of tumor reduction during treatment. We considered 12 statistics features and 230 textural features extracted from the CT images. In our study, we used an ensemble learning method to classify patients' data into either the adaptive or non-adaptive group during chemoradiation on the basis of the starting CT simulation. Our data supports the hypothesis that a specific signature can be identified (AUC 0.82). In our experience, a radiomic signature mixing semantic and image-based features has shown promising results for personalized adaptive radiotherapy in non-small cell lung cancer.

A decision support system for type 1 diabetes mellitus diagnostics based on dual channel analysis of red blood cell membrane fluidity.

BACKGROUND AND OBJECTIVE: Investigation of membrane fluidity by metabolic functional imaging opens up a new and important area of translational research in type 1 diabetes mellitus, being a useful and sensitive biomarker for disease monitoring and treatment. We investigate here how data on membrane fluidity can be used for diabetes monitoring. METHODS: We present a decision support system that distinguishes between healthy subjects, type 1 diabetes mellitus patients, and type 1 diabetes mellitus patients with complications. It leverages on dual channel data computed from the physical state of human red blood cells membranes by means of features based on first- and second-order statistical measures as well as on rotation invariant co-occurrence local binary patterns. The experiments were carried out on a dataset of more than 1000 images belonging to 27 subjects. RESULTS: Our method shows a global accuracy of 100%, outperforming also the state-of-the-art approach based on the glycosylated hemoglobin. CONCLUSIONS: The proposed recognition approach permits to achieve promising results.

Phase separation of the plasma membrane in human red blood cells as a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus.

Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins can alter lipid density, packing and interactions, and are considered an important factor that affects fluidity variation in membranes. Red blood cells (RBC) membrane physical state, showing pronounced alterations in Type 1 diabetes mellitus (T1DM), could be the ideal candidate for monitoring the disease progression and the effects of therapies. On these grounds, the measurement of RBC membrane fluidity alterations can furnish a more sensitive index in T1DM diagnosis and disease progression than Glycosylated hemoglobin (HbA1c), which reflects only the information related to glycosylation processes. Here, through a functional two-photon microscopy approach we retrieved fluidity maps at submicrometric scale in RBC of T1DM patients with and without complications, detecting an altered membrane equilibrium. We found that a phase separation between fluid and rigid domains occurs, triggered by systemic effects on membranes fluidity of glycation and oxidation. The phase separation patterns are different among healthy, T1DM and T1DM with complications patients. Blood cholesterol and LDL content are positively correlated with the extent of the phase separation patterns. To quantify this extent a machine learning approach is employed to develop a Decision-Support-System (DSS) able to recognize different fluidity patterns in RBC. Preliminary analysis shows significant differences(p<0.001) among healthy, T1DM and T1DM with complications patients. The development of an assay based on Phase separation of the plasma membrane of the Red Blood cells is a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus, and could allow customization and the selection of medical treatments in T1DM in clinical settings, and enable the early detection of complications.

Computer-based automatic identification of neurons in gigavoxel-sized 3D human brain images.

Achieving a comprehensive knowledge of the human brain cytoarchitecture is a fundamental step to understand how the nervous system works, i.e., one of the greatest challenge of 21(st) century science. The recent development of biological tissue labeling and automated microscopic imaging systems has permitted to acquire images at the micro-resolution, which produce a huge quantity of data that cannot be manually analyzed. In case of mammals brain, automatic methods to extract objective information at the microscale have been applied until now to mice, macaque and cat 3D volume images. Here we report a method to automatically localize neurons in a sample of human brain removed during a surgical procedure for the treatments of drug resistant epilepsy in a child with hemimegalencephaly, whose neurons and neurites were fluorescence labelled and finally imaged using the two-photon fluorescence microscope. The method provides the map of both parvalbuminergic neurons and all other cells nuclei with a satisfactory f-score measured using more than two thousand human labelled soma.