On-cloud decision-support system for non-small cell lung cancer histology characterization from thorax computed tomography scans

Non-Small Cell Lung Cancer (NSCLC) accounts for about 85% of all lung cancers. Developing non-invasive techniques for NSCLC histology characterization may not only help clinicians to make targeted therapeutic treatments but also prevent subjects from undergoing lung biopsy, which is challenging and could lead to clinical implications. The motivation behind the study presented here is to develop an advanced on-cloud decisionsupport system, named LUCY, for non-small cell LUng Cancer histologY characterization directly from thorax Computed Tomography (CT) scans. This aim was pursued by selecting thorax CT scans of 182 LUng ADenocarcinoma (LUAD) and 186 LUng Squamous Cell carcinoma (LUSC) subjects from four openly accessible data collections (NSCLC-Radiomics, NSCLC-Radiogenomics, NSCLC-Radiomics-Genomics and TCGA-LUAD), in addition to the implementation and comparison of two end-to-end neural networks (the core layer of whom is a convolutional long short-term memory layer), the performance evaluation on test dataset (NSCLC-RadiomicsGenomics) from a subject-level perspective in relation to NSCLC histological subtype location and grade, and the dynamic visual interpretation of the achieved results by producing and analyzing one heatmap video for each scan. LUCY reached test Area Under the receiver operating characteristic Curve (AUC) values above 77% in all NSCLC histological subtype location and grade groups, and a best AUC value of 97% on the entire dataset reserved for testing, proving high generalizability to heterogeneous data and robustness. Thus, LUCY is a clinically-useful decision-support system able to timely, non-invasively and reliably provide visuallyunderstandable predictions on LUAD and LUSC subjects in relation to clinically-relevant information

Lung nodule diagnosis and cancer histology classification from computed tomography data by convolutional neural networks: A survey

Lung cancer is among the deadliest cancers. Besides lung nodule classification and diagnosis, developing non-invasive systems to classify lung cancer histological types/subtypes may help clinicians to make targeted treatment decisions timely, having a positive impact on patients' comfort and survival rate. As convolutional neural networks have proven to be responsible for the significant improvement of the accuracy in lung cancer diagnosis, with this survey we intend to: show the contribution of convolutional neural networks not only in identifying malignant lung nodules but also in classifying lung cancer histological types/subtypes directly from computed tomography data; point out the strengths and weaknesses of slice-based and scan-based approaches employing convolutional neural networks; and highlight the challenges and prospective solutions to successfully apply convolutional neural networks for such classification tasks. To this aim, we conducted a comprehensive analysis of relevant Scopus-indexed studies involved in lung nodule diagnosis and cancer histology classification up to January 2022, dividing the investigation in convolutional neural network-based approaches fed with planar or volumetric computed tomography data. Despite the application of convolutional neural networks in lung nodule diagnosis and cancer histology classification is a valid strategy, some challenges raised, mainly including the lack of publicly-accessible annotated data, together with the lack of reproducibility and clinical interpretability. We believe that this survey will be helpful for future studies involved in lung nodule diagnosis and cancer histology classification prior to lung biopsy by means of convolutional neural networks

Pulmonary Large Cell Neuroendocrine Carcinoma:a unique type of lung cancer? Identification of molecular and clinical subtypes & consequences for treatment

About 1-3% of all new cases of lung cancer are large cell neuroendocrine carcinoma (LCNEC). This is an aggressive form of lung cancer; patients with metastatic disease have an average of 4-9 months to live after diagnosis. The treatment for them currently consists of chemotherapy as we also use for other forms of lung cancer. This dissertation studied similarities and differences between LCNEC and other forms of (lung) cancer. Through more clarity about these similarities and differences, it can be better predicted to which type of treatment LCNEC patients will respond well. Also, different subgroups of LCNEC are distinguished. Patients in these subgroups may also benefit from a slightly different treatment. LCNEC appears to be a form of lung cancer with unique characteristics, but also with a clear overlap with other forms of lung cancer

Enhanced Convolutional Neural Network for Non-Small Cell Lung Cancer Classification

Lung cancer is a common type of cancer that causes death if not detectedearly enough. Doctors use computed tomography (CT) images to diagnoselung cancer. The accuracy of the diagnosis relies highly on the doctor\u27sexpertise. Recently, clinical decision support systems based on deep learningvaluable recommendations to doctors in their diagnoses. In this paper, wepresent several deep learning models to detect non-small cell lung cancer inCT images and differentiate its main subtypes namely adenocarcinoma,large cell carcinoma, and squamous cell carcinoma. We adopted standardconvolutional neural networks (CNN), visual geometry group-16 (VGG16),and VGG19. Besides, we introduce a variant of the CNN that is augmentedwith convolutional block attention modules (CBAM). CBAM aims to extractinformative features by combining cross-channel and spatial information.We also propose variants of VGG16 and VGG19 that utilize a supportvector machine (SVM) at the classification layer instead of SoftMax. Wevalidated all models in this study through extensive experiments on a CTlung cancer dataset. Experimental results show that supplementing CNNwith CBAM leads to consistent improvements over vanilla CNN. Resultsalso show that the VGG variants that use the SVM classifier outperform theoriginal VGGs by a significant margin

Role of machine learning in early diagnosis of kidney diseases.

Machine learning (ML) and deep learning (DL) approaches have been used as indispensable tools in modern artificial intelligence-based computer-aided diagnostic (AIbased CAD) systems that can provide non-invasive, early, and accurate diagnosis of a given medical condition. These AI-based CAD systems have proven themselves to be reproducible and have the generalization ability to diagnose new unseen cases with several diseases and medical conditions in different organs (e.g., kidneys, prostate, brain, liver, lung, breast, and bladder). In this dissertation, we will focus on the role of such AI-based CAD systems in early diagnosis of two kidney diseases, namely: acute rejection (AR) post kidney transplantation and renal cancer (RC). A new renal computer-assisted diagnostic (Renal-CAD) system was developed to precisely diagnose AR post kidney transplantation at an early stage. The developed Renal-CAD system perform the following main steps: (1) auto-segmentation of the renal allograft from surrounding tissues from diffusion weighted magnetic resonance imaging (DW-MRI) and blood oxygen level-dependent MRI (BOLD-MRI), (2) extraction of image markers, namely: voxel-wise apparent diffusion coefficients (ADCs) are calculated from DW-MRI scans at 11 different low and high b-values and then represented as cumulative distribution functions (CDFs) and extraction of the transverse relaxation rate (R2*) values from the segmented kidneys using BOLD-MRI scans at different echotimes, (3) integration of multimodal image markers with the associated clinical biomarkers, serum creatinine (SCr) and creatinine clearance (CrCl), and (4) diagnosing renal allograft status as nonrejection (NR) or AR by utilizing these integrated biomarkers and the developed deep learning classification model built on stacked auto-encoders (SAEs). Using a leaveone- subject-out cross-validation approach along with SAEs on a total of 30 patients with transplanted kidney (AR = 10 and NR = 20), the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified 10-fold cross-validation approach, the Renal-CAD system demonstrated its reproduciblity and robustness with a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88. In addition, a new renal cancer CAD (RC-CAD) system for precise diagnosis of RC at an early stage was developed, which incorporates the following main steps: (1) estimating the morphological features by applying a new parametric spherical harmonic technique, (2) extracting appearance-based features, namely: first order textural features are calculated and second order textural features are extracted after constructing the graylevel co-occurrence matrix (GLCM), (3) estimating the functional features by constructing wash-in/wash-out slopes to quantify the enhancement variations across different contrast enhanced computed tomography (CE-CT) phases, (4) integrating all the aforementioned features and modeling a two-stage multilayer perceptron artificial neural network (MLPANN) classifier to classify the renal tumor as benign or malignant and identify the malignancy subtype. On a total of 140 RC patients (malignant = 70 patients (ccRCC = 40 and nccRCC = 30) and benign angiomyolipoma tumors = 70), the developed RC-CAD system was validated using a leave-one-subject-out cross-validation approach. The developed RC-CAD system achieved a sensitivity of 95.3% ± 2.0%, a specificity of 99.9% ± 0.4%, and Dice similarity coefficient of 0.98 ± 0.01 in differentiating malignant from benign renal tumors, as well as an overall accuracy of 89.6% ± 5.0% in the sub-typing of RCC. The diagnostic abilities of the developed RC-CAD system were further validated using a randomly stratified 10-fold cross-validation approach. The results obtained using the proposed MLP-ANN classification model outperformed other machine learning classifiers (e.g., support vector machine, random forests, and relational functional gradient boosting) as well as other different approaches from the literature. In summary, machine and deep learning approaches have shown potential abilities to be utilized to build AI-based CAD systems. This is evidenced by the promising diagnostic performance obtained by both Renal-CAD and RC-CAD systems. For the Renal- CAD, the integration of functional markers extracted from multimodal MRIs with clinical biomarkers using SAEs classification model, potentially improved the final diagnostic results evidenced by high accuracy, sensitivity, and specificity. The developed Renal-CAD demonstrated high feasibility and efficacy for early, accurate, and non-invasive identification of AR. For the RC-CAD, integrating morphological, textural, and functional features extracted from CE-CT images using a MLP-ANN classification model eventually enhanced the final results in terms of accuracy, sensitivity, and specificity, making the proposed RC-CAD a reliable noninvasive diagnostic tool for RC. The early and accurate diagnosis of AR or RC will help physicians to provide early intervention with the appropriate treatment plan to prolong the life span of the diseased kidney, increase the survival chance of the patient, and thus improve the healthcare outcome in the U.S. and worldwide

Radiogenomics Framework for Associating Medical Image Features with Tumour Genetic Characteristics

Significant progress has been made in the understanding of human cancers at the molecular genetics level and it is providing new insights into their underlying pathophysiology. This progress has enabled the subclassification of the disease and the development of targeted therapies that address specific biological pathways. However, obtaining genetic information remains invasive and costly. Medical imaging is a non-invasive technique that captures important visual characteristics (i.e. image features) of abnormalities and plays an important role in routine clinical practice. Advancements in computerised medical image analysis have enabled quantitative approaches to extract image features that can reflect tumour genetic characteristics, leading to the emergence of ‘radiogenomics’. Radiogenomics investigates the relationships between medical imaging features and tumour molecular characteristics, and enables the derivation of imaging surrogates (radiogenomics features) to genetic biomarkers that can provide alternative approaches to non-invasive and accurate cancer diagnosis. This thesis presents a new framework that combines several novel methods for radiogenomics analysis that associates medical image features with tumour genetic characteristics, with the main objectives being: i) a comprehensive characterisation of tumour image features that reflect underlying genetic information; ii) a method that identifies radiogenomics features encoding common pathophysiological information across different diseases, overcoming the dependence on large annotated datasets; and iii) a method that quantifies radiogenomics features from multi-modal imaging data and accounts for unique information encoded in tumour heterogeneity sub-regions. The present radiogenomics methods advance radiogenomics analysis and contribute to improving research in computerised medical image analysis