Virtual biopsy in abdominal pathology: where do we stand?

In recent years, researchers have explored new ways to obtain information from pathological tissues, also exploring non-invasive techniques, such as virtual biopsy (VB). VB can be defined as a test that provides promising outcomes compared to traditional biopsy by extracting quantitative information from radiological images not accessible through traditional visual inspection. Data are processed in such a way that they can be correlated with the patient’s phenotypic expression, or with molecular patterns and mutations, creating a bridge between traditional radiology, pathology, genomics, and artificial intelligence (AI). Radiomics is the backbone of VB, since it allows the extraction and selection of features from radiological images, feeding them into AI models in order to derive lesions' pathological characteristics and molecular status. Presently, the output of VB provides only a gross approximation of the findings of tissue biopsy. However, in the future, with the improvement of imaging resolution and processing techniques, VB could partially substitute the classical surgical or percutaneous biopsy, with the advantage of being non-invasive, comprehensive, accounting for lesion heterogeneity, and low cost. In this review, we investigate the concept of VB in abdominal pathology, focusing on its pipeline development and potential benefits

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

Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review

Background: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology. Materials and methods: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data. Results: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data. Conclusion: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice

Role of Artificial Intelligence in Radiogenomics for Cancers in the Era of Precision Medicine

Radiogenomics, a combination of “Radiomics” and “Genomics,” using Artificial Intelligence (AI) has recently emerged as the state-of-the-art science in precision medicine, especially in oncology care. Radiogenomics syndicates large-scale quantifiable data extracted from radiological medical images enveloped with personalized genomic phenotypes. It fabricates a prediction model through various AI methods to stratify the risk of patients, monitor therapeutic approaches, and assess clinical outcomes. It has recently shown tremendous achievements in prognosis, treatment planning, survival prediction, heterogeneity analysis, reoccurrence, and progression-free survival for human cancer study. Although AI has shown immense performance in oncology care in various clinical aspects, it has several challenges and limitations. The proposed review provides an overview of radiogenomics with the viewpoints on the role of AI in terms of its promises for computa-tional as well as oncological aspects and offers achievements and opportunities in the era of precision medicine. The review also presents various recommendations to diminish these obstacles

AI-basierte volumetrische Analyse der Lebermetastasenlast bei Patienten mit neuroendokrinen Neoplasmen (NEN)

Background: Quantification of liver tumor load in patients with liver metastases from neuroendocrine neoplasms is essential for therapeutic management. However, accurate measurement of three-dimensional (3D) volumes is time-consuming and difficult to achieve. Even though the common criteria for assessing treatment response have simplified the measurement of liver metastases, the workload of following up patients with neuroendocrine liver metastases (NELMs) remains heavy for radiologists due to their increased morbidity and prolonged survival. Among the many imaging methods, gadoxetic acid (Gd-EOB)-enhanced magnetic resonance imaging (MRI) has shown the highest accuracy. Methods: 3D-volumetric segmentation of NELM and livers were manually performed in 278 Gd-EOB MRI scans from 118 patients. Eighty percent (222 scans) of them were randomly divided into training datasets and the other 20% (56 scans) were internal validation datasets. An additional 33 patients from a different time period, who underwent Gd-EOB MRI at both baseline and 12-month follow-up examinations, were collected for external and clinical validation (n = 66). Model measurement results (NELM volume; hepatic tumor load (HTL)) and the respective absolute (ΔabsNELM; ΔabsHTL) and relative changes (ΔrelNELM; ΔrelHTL) for baseline and follow-up-imaging were used and correlated with multidisciplinary cancer conferences (MCC) decisions (treatment success/failure). Three readers manually segmented MRI images of each slice, blinded to clinical data and independently. All images were reviewed by another senior radiologist. Results: The model’s performance showed high accuracy between NELM and liver in both internal and external validation (Matthew’s correlation coefficient (ϕ): 0.76/0.95, 0.80/0.96, respectively). And in internal validation dataset, the group with higher NELM volume (> 16.17 cm3) showed higher ϕ than the group with lower NELM volume (ϕ = 0.80 vs. 0.71; p = 0.0025). In the external validation dataset, all response variables (∆absNELM; ∆absHTL; ∆relNELM; ∆relHTL) reflected significant differences across MCC decision groups (all p < 0.001). The AI model correctly detected the response trend based on ∆relNELM and ∆relHTL in all the 33 MCC patients and showed the optimal discrimination between treatment success and failure at +56.88% and +57.73%, respectively (AUC: 1.000; P < 0.001). Conclusions: The created AI-based segmentation model performed well in the three-dimensional quantification of NELMs and HTL in Gd-EOB-MRI. Moreover, the model showed good agreement with the evaluation of treatment response of the MCC’s decision.Hintergrund: Die Quantifizierung der Lebertumorlast bei Patienten mit Lebermetastasen von neuroendokrinen Neoplasien ist für die Behandlung unerlässlich. Eine genaue Messung des dreidimensionalen (3D) Volumens ist jedoch zeitaufwändig und schwer zu erreichen. Obwohl standardisierte Kriterien für die Beurteilung des Ansprechens auf die Behandlung die Messung von Lebermetastasen vereinfacht haben, bleibt die Arbeitsbelastung für Radiologen bei der Nachbeobachtung von Patienten mit neuroendokrinen Lebermetastasen (NELMs) aufgrund der höheren Fallzahlen durch erhöhte Morbidität und verlängerter Überlebenszeit hoch. Unter den zahlreichen bildgebenden Verfahren hat die Gadoxetsäure (Gd-EOB)-verstärkte Magnetresonanztomographie (MRT) die höchste Genauigkeit gezeigt. Methoden: Manuelle 3D-Segmentierungen von NELM und Lebern wurden in 278 Gd-EOB-MRT-Scans von 118 Patienten durchgeführt. 80% (222 Scans) davon wurden nach dem Zufallsprinzip in den Trainingsdatensatz eingeteilt, die übrigen 20% (56 Scans) waren interne Validierungsdatensätze. Zur externen und klinischen Validierung (n = 66) wurden weitere 33 Patienten aus einer späteren Zeitspanne des Multidisziplinäre Krebskonferenzen (MCC) erfasst, welche sich sowohl bei der Erstuntersuchung als auch bei der Nachuntersuchung nach 12 Monaten einer Gd-EOB-MRT unterzogen hatten. Die Messergebnisse des Modells (NELM-Volumen; hepatische Tumorlast (HTL)) mit den entsprechenden absoluten (ΔabsNELM; ΔabsHTL) und relativen Veränderungen (ΔrelNELM; ΔrelHTL) bei der Erstuntersuchung und der Nachuntersuchung wurden zum Vergleich mit MCC-Entscheidungen (Behandlungserfolg/-versagen) herangezogen. Drei Leser segmentierten die MRT-Bilder jeder Schicht manuell, geblindet und unabhängig. Alle Bilder wurden von einem weiteren Radiologen überprüft. Ergebnisse: Die Leistung des Modells zeigte sowohl bei der internen als auch bei der externen Validierung eine hohe Genauigkeit zwischen NELM und Leber (Matthew's Korrelationskoeffizient (ϕ): 0,76/0,95 bzw. 0,80/0,96). Und im internen Validierungsdatensatz zeigte die Gruppe mit höherem NELM-Volumen (> 16,17 cm3) einen höheren ϕ als die Gruppe mit geringerem NELM-Volumen (ϕ = 0,80 vs. 0,71; p = 0,0025). Im externen Validierungsdatensatz wiesen alle Antwortvariablen (∆absNELM; ∆absHTL; ∆relNELM; ∆relHTL) signifikante Unterschiede zwischen den MCC-Entscheidungsgruppen auf (alle p < 0,001). Das KI-Modell erkannte das Therapieansprechen auf der Grundlage von ∆relNELM und ∆relHTL bei allen 33 MCC-Patienten korrekt und zeigte bei +56,88% bzw. +57,73% eine optimale Unterscheidung zwischen Behandlungserfolg und -versagen (AUC: 1,000; P < 0,001). Schlussfolgerungen: Das Modell zeigte eine hohe Genauigkeit bei der dreidimensionalen Quantifizierung des NELMs-Volumens und der HTL in der Gd-EOB-MRT. Darüber hinaus zeigte das Modell eine gute Übereinstimmung bei der Bewertung des Ansprechens auf die Behandlung mit der Entscheidung des Tumorboards

Dynamic And Quantitative Radiomics Analysis In Interventional Radiology

Interventional Radiology (IR) is a subspecialty of radiology that performs invasive procedures driven by diagnostic imaging for predictive and therapeutic purpose. The development of artificial intelligence (AI) has revolutionized the industry of IR. Researchers have created sophisticated models backed by machine learning algorithms and optimization methodologies for image registration, cellular structure detection and computer-aided disease diagnosis and prognosis predictions. However, due to the incapacity of the human eye to detect tiny structural characteristics and inter-radiologist heterogeneity, conventional experience-based IR visual evaluations may have drawbacks. Radiomics, a technique that utilizes machine learning, offers a practical and quantifiable solution to this issue. This technology has been used to evaluate the heterogeneity of malignancies that are difficult to detect by the human eye by creating an automated pipeline for the extraction and analysis of high throughput computational imaging characteristics from radiological medical pictures. However, it is a demanding task to directly put radiomics into applications in IR because of the heterogeneity and complexity of medical imaging data. Furthermore, recent radiomics studies are based on static images, while many clinical applications (such as detecting the occurrence and development of tumors and assessing patient response to chemotherapy and immunotherapy) is a dynamic process. Merely incorporating static features cannot comprehensively reflect the metabolic characteristics and dynamic processes of tumors or soft tissues. To address these issues, we proposed a robust feature selection framework to manage the high-dimensional small-size data. Apart from that, we explore and propose a descriptor in the view of computer vision and physiology by integrating static radiomics features with time-varying information in tumor dynamics. The major contributions to this study include: Firstly, we construct a result-driven feature selection framework, which could efficiently reduce the dimension of the original feature set. The framework integrates different feature selection techniques to ensure the distinctiveness, uniqueness, and generalization ability of the output feature set. In the task of classification hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in primary liver cancer, only three radiomics features (chosen from more than 1, 800 features of the proposed framework) can obtain an AUC of 0.83 in the independent dataset. Besides, we also analyze features’ pattern and contributions to the results, enhancing clinical interpretability of radiomics biomarkers. Secondly, we explore and build a pulmonary perfusion descriptor based on 18F-FDG whole-body dynamic PET images. Our major novelties include: 1) propose a physiology-and-computer-vision-interpretable descriptor construction framework by the decomposition of spatiotemporal information into three dimensions: shades of grey levels, textures, and dynamics. 2) The spatio-temporal comparison of pulmonary descriptor intra and inter patients is feasible, making it possible to be an auxiliary diagnostic tool in pulmonary function assessment. 3) Compared with traditional PET metabolic biomarker analysis, the proposed descriptor incorporates image’s temporal information, which enables a better understanding of the time-various mechanisms and detection of visual perfusion abnormalities among different patients. 4) The proposed descriptor eliminates the impact of vascular branching structure and gravity effect by utilizing time warping algorithms. Our experimental results showed that our proposed framework and descriptor are promising tools to medical imaging analysis

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

Bioinformatics and Machine Learning for Cancer Biology

Cancer is a leading cause of death worldwide, claiming millions of lives each year. Cancer biology is an essential research field to understand how cancer develops, evolves, and responds to therapy. By taking advantage of a series of “omics” technologies (e.g., genomics, transcriptomics, and epigenomics), computational methods in bioinformatics and machine learning can help scientists and researchers to decipher the complexity of cancer heterogeneity, tumorigenesis, and anticancer drug discovery. Particularly, bioinformatics enables the systematic interrogation and analysis of cancer from various perspectives, including genetics, epigenetics, signaling networks, cellular behavior, clinical manifestation, and epidemiology. Moreover, thanks to the influx of next-generation sequencing (NGS) data in the postgenomic era and multiple landmark cancer-focused projects, such as The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), machine learning has a uniquely advantageous role in boosting data-driven cancer research and unraveling novel methods for the prognosis, prediction, and treatment of cancer