Radiotranscriptomics of non-small cell lung carcinoma for assessing high-level clinical outcomes using a machine learning-derived multi-modal signature.

BACKGROUND: Multi-omics research has the potential to holistically capture intra-tumor variability, thereby improving therapeutic decisions by incorporating the key principles of precision medicine. The purpose of this study is to identify a robust method of integrating features from different sources, such as imaging, transcriptomics, and clinical data, to predict the survival and therapy response of non-small cell lung cancer patients. METHODS: 2996 radiomics, 5268 transcriptomics, and 8 clinical features were extracted from the NSCLC Radiogenomics dataset. Radiomics and deep features were calculated based on the volume of interest in pre-treatment, routine CT examinations, and then combined with RNA-seq and clinical data. Several machine learning classifiers were used to perform survival analysis and assess the patient's response to adjuvant chemotherapy. The proposed analysis was evaluated on an unseen testing set in a k-fold cross-validation scheme. Score- and concatenation-based multi-omics were used as feature integration techniques. RESULTS: Six radiomics (elongation, cluster shade, entropy, variance, gray-level non-uniformity, and maximal correlation coefficient), six deep features (NasNet-based activations), and three transcriptomics (OTUD3, SUCGL2, and RQCD1) were found to be significant for therapy response. The examined score-based multi-omic improved the AUC up to 0.10 on the unseen testing set (0.74 ± 0.06) and the balance between sensitivity and specificity for predicting therapy response for 106 patients, resulting in less biased models and improving upon the either highly sensitive or highly specific single-source models. Six radiomics (kurtosis, GLRLM- and GLSZM-based non-uniformity from images with no filtering, biorthogonal, and daubechies wavelets), seven deep features (ResNet-based activations), and seven transcriptomics (ELP3, ZZZ3, PGRMC2, TRAK1, ATIC, USP7, and PNPLA2) were found to be significant for the survival analysis. Accordingly, the survival analysis for 115 patients was also enhanced up to 0.20 by the proposed score-based multi-omics in terms of the C-index (0.79 ± 0.03). CONCLUSIONS: Compared to single-source models, multi-omics integration has the potential to improve prediction performance, increase model stability, and reduce bias for both treatment response and survival analysis.

Enhancing cancer differentiation with synthetic MRI examinations via generative models: a systematic review.

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.

Deep Radiotranscriptomics of Non-Small Cell Lung Carcinoma for Assessing Molecular and Histology Subtypes with a Data-Driven Analysis.

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.

Emerging deep learning techniques using magnetic resonance imaging data applied in multiple sclerosis and clinical isolated syndrome patients (Review).

Computer-aided diagnosis systems aim to assist clinicians in the early identification of abnormal signs in order to optimize the interpretation of medical images and increase diagnostic precision. Multiple sclerosis (MS) and clinically isolated syndrome (CIS) are chronic inflammatory, demyelinating diseases affecting the central nervous system. Recent advances in deep learning (DL) techniques have led to novel computational paradigms in MS and CIS imaging designed for automatic segmentation and detection of areas of interest and automatic classification of anatomic structures, as well as optimization of neuroimaging protocols. To this end, there are several publications presenting artificial intelligence-based predictive models aiming to increase diagnostic accuracy and to facilitate optimal clinical management in patients diagnosed with MS and/or CIS. The current study presents a thorough review covering DL techniques that have been applied in MS and CIS during recent years, shedding light on their current advances and limitations.

A neural pathomics framework for classifying colorectal cancer histopathology images based on wavelet multi-scale texture analysis.

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.

Cerebral CT Perfusion in Acute Stroke: The Effect of Lowering the Tube Load and Sampling Rate on the Reproducibility of Parametric Maps.

The aim of this study was to define lower dose parameters (tube load and temporal sampling) for CT perfusion that still preserve the diagnostic efficiency of the derived parametric maps. Ninety stroke CT examinations from four clinical sites with 1 s temporal sampling and a range of tube loads (mAs) (100-180) were studied. Realistic CT noise was retrospectively added to simulate a CT perfusion protocol, with a maximum reduction of 40% tube load (mAs) combined with increased sampling intervals (up to 3 s). Perfusion maps from the original and simulated protocols were compared by: (a) similarity using a voxel-wise Pearson's correlation coefficient r with in-house software; (b) volumetric analysis of the infarcted and hypoperfused volumes using commercial software. Pearson's r values varied for the different perfusion metrics from 0.1 to 0.85. The mean slope of increase and cerebral blood volume present the highest r values, remaining consistently above 0.7 for all protocol versions with 2 s sampling interval. Reduction of the sampling rate from 2 s to 1 s had only modest impacts on a TMAX volume of 0.4 mL (IQR -1-3) (p = 0.04) and core volume of -1.1 mL (IQR -4-0) (p < 0.001), indicating dose savings of 50%, with no practical loss of diagnostic accuracy. The lowest possible dose protocol was 2 s temporal sampling and a tube load of 100 mAs.

Advancing COVID-19 differentiation with a robust preprocessing and integration of multi-institutional open-repository computer tomography datasets for deep learning analysis.

The coronavirus pandemic and its unprecedented consequences globally has spurred the interest of the artificial intelligence research community. A plethora of published studies have investigated the role of imaging such as chest X-rays and computer tomography in coronavirus disease 2019 (COVID-19) automated diagnosis. Οpen repositories of medical imaging data can play a significant role by promoting cooperation among institutes in a world-wide scale. However, they may induce limitations related to variable data quality and intrinsic differences due to the wide variety of scanner vendors and imaging parameters. In this study, a state-of-the-art custom U-Net model is presented with a dice similarity coefficient performance of 99.6% along with a transfer learning VGG-19 based model for COVID-19 versus pneumonia differentiation exhibiting an area under curve of 96.1%. The above was significantly improved over the baseline model trained with no segmentation in selected tomographic slices of the same dataset. The presented study highlights the importance of a robust preprocessing protocol for image analysis within a heterogeneous imaging dataset and assesses the potential diagnostic value of the presented COVID-19 model by comparing its performance to the state of the art.

Interpretable artificial intelligence framework for COVID-19 screening on chest X-rays.

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.

Artificial intelligence radiogenomics for advancing precision and effectiveness in oncologic care (Review).

The new era of artificial intelligence (AI) has introduced revolutionary data­driven analysis paradigms that have led to significant advancements in information processing techniques in the context of clinical decision­support systems. These advances have created unprecedented momentum in computational medical imaging applications and have given rise to new precision medicine research areas. Radiogenomics is a novel research field focusing on establishing associations between radiological features and genomic or molecular expression in order to shed light on the underlying disease mechanisms and enhance diagnostic procedures towards personalized medicine. The aim of the current review was to elucidate recent advances in radiogenomics research, focusing on deep learning with emphasis on radiology and oncology applications. The main deep learning radiogenomics architectures, together with the clinical questions addressed, and the achieved genetic or molecular correlations are presented, while a performance comparison of the proposed methodologies is conducted. Finally, current limitations, potentially understudied topics and future research directions are discussed.

A novel deep learning architecture outperforming 'off­the­shelf' transfer learning and feature­based methods in the automated assessment of mammographic breast density.

Potentially suspicious breast neoplasms could be masked by high tissue density, thus increasing the probability of a false­negative diagnosis. Furthermore, differentiating breast tissue type enables patient pre­screening stratification and risk assessment. In this study, we propose and evaluate advanced machine learning methodologies aiming at an objective and reliable method for breast density scoring from routine mammographic images. The proposed image analysis pipeline incorporates texture [Gabor filters and local binary pattern (LBP)] and gradient­based features [histogram of oriented gradients (HOG) as well as speeded­up robust features (SURF)]. Additionally, transfer learning approaches with ImageNet trained weights were also used for comparison, as well as a convolutional neural network (CNN). The proposed CNN model was fully trained on two open mammography datasets and was found to be the optimal performing methodology (AUC up to 87.3%). Thus, the findings of this study indicate that automated density scoring in mammograms can aid clinical diagnosis by introducing artificial intelligence­powered decision­support systems and contribute to the 'democratization' of healthcare by overcoming limitations, such as the geographic location of patients or the lack of expert radiologists.

Extending 2-D Convolutional Neural Networks to 3-D for Advancing Deep Learning Cancer Classification With Application to MRI Liver Tumor Differentiation.

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