Tissue Biomarkers are information written in the tissue and used in Pathology to recognize specific subsets of patients with diagnostic, prognostic or predictive purposes, thus representing the key elements of Personalized Medicine. The advent of Artificial Intelligence (AI) promises to further reinforce the role of Pathology in the scenario of Personalized Medicine: AI-based devices are expected to standardize the evaluation of tissue biomarkers and also to discover novel information, which would otherwise be ignored by human review, and use them to make specific predictions. In this review we will present how AI has been used to support Tissue Biomarkers evaluation in the specific field of Pathology, give an insight to the intriguing field of AI-based biomarkers and discuss possible advantages, risk and perspectives for Pathology.

Diagnostic imaging is regarded as fundamental in the clinical work-up of patients with a suspected or confirmed COVID-19 infection. Recent progress has been made in diagnostic imaging with the integration of artificial intelligence (AI) and machine learning (ML) algorisms leading to an increase in the accuracy of exam interpretation and to the extraction of prognostic information useful in the decision-making process. Considering the ever expanding imaging data generated amid this pandemic, COVID-19 has catalyzed the rapid expansion in the application of AI to combat disease. In this context, many recent studies have explored the role of AI in each of the presumed applications for COVID-19 infection chest imaging, suggesting that implementing AI applications for chest imaging can be a great asset for fast and precise disease screening, identification and characterization. However, various biases should be overcome in the development of further ML-based algorithms to give them sufficient robustness and reproducibility for their integration into clinical practice. As a result, in this literature review, we will focus on the application of AI in chest imaging, in particular, deep learning, radiomics and advanced imaging as quantitative CT.

Background and Aims: Coronary thin-cap fibroatheromas (TCFA) are associated with adverse outcome, but identification of TCFA requires expertise and is highly time-demanding. This study evaluated the utility of artificial intelligence (AI) for TCFA identification in relation to clinical outcome. Methods: The PECTUS-AI study is a secondary analysis from the prospective observational PECTUS-obs study, in which 438 patients with myocardial infarction underwent optical coherence tomography (OCT) of all fractional flow reserve-negative non-culprit lesions (i.e. target lesions). OCT images were analyzed for the presence of TCFA by an independent core laboratory (CL-TCFA) and OCT-AID, a recently developed and validated AI segmentation algorithm (AI-TCFA). The primary outcome was defined as the composite of death from any cause, non-fatal myocardial infarction or unplanned revascularisation at 2 years (±30 days), excluding procedural and stent-related events. Results: Among 414 patients, AI-TCFA and CL-TCFA were identified in 143 (34.5%) and 124 (30.0%) patients, respectively. AI-TCFA within the target lesion was significantly associated with the primary outcome [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.02–3.90, P = .04], while the HR for CL-TCFA was non-significant (1.67, 95% CI: .84–3.30, P = .14). When evaluating the complete pullback, AI-TCFA showed an even stronger association with the primary outcome (HR 5.50, 95% CI: 1.94–15.62, P < .001; negative predictive value 97.6%, 95% CI: 94.0%–99.3%). Conclusions: AI-based OCT image analysis allows standardized identification of patients at increased risk of adverse cardiovascular outcome, offering an alternative to manual image analysis. Furthermore, AI-assisted evaluation of complete imaged segments results in better prognostic discrimatory value than evaluation of the target lesion only.

Intracoronary optical coherence tomography (OCT) is a valuable tool for, among others, periprocedural guidance of percutaneous coronary revascularization and the assessment of stent failure. However, manual OCT image interpretation is challenging and time-consuming, which limits widespread clinical adoption. Automated analysis of OCT frames using artificial intelligence (AI) offers a potential solution. For example, AI can be employed for automated OCT image interpretation, plaque quantification, and clinical event prediction. Many AI models for these purposes have been proposed in recent years. However, these models have not been systematically evaluated in terms of model characteristics, performances, and bias. We performed a systematic review of AI models developed for OCT analysis to evaluate the trends and performances, including a systematic evaluation of potential sources of bias in model development and evaluation.

Aims: Intracoronary optical coherence tomography (OCT) provides detailed information on coronary lesions, but interpretation of OCT images is time-consuming and subject to interobserver variability. The aim of this study was to develop and validate a deep learning-based multiclass semantic segmentation algorithm for OCT (OCT-AID). Methods and results: A reference standard was obtained through manual multiclass annotation (guidewire artefact, lumen, side branch, intima, media, lipid plaque, calcified plaque, thrombus, plaque rupture, and background) of OCT images from a representative subset of pullbacks from the PECTUS-obs study. Pullbacks were randomly divided into a training and internal test set. An additional independent dataset was used for external testing. In total, 2808 frames were used for training and 218 for internal testing. The external test set comprised 392 frames. On the internal test set, the mean Dice score across nine classes was 0.659 overall and 0.757 on the true-positive frames, ranging from 0.281 to 0.989 per class. Substantial to almost perfect agreement was achieved for frame-wise identification of both lipid (κ=0.817, 95% CI 0.743–0.891) and calcified plaques (κ=0.795, 95% CI 0.703–0.887). For plaque quantification (e.g. lipid arc, calcium thickness), intraclass correlations of 0.664–0.884 were achieved. In the external test set, κ-values for lipid and calcified plaques were 0.720 (95% CI 0.640–0.800) and 0.851 (95% CI 0.794–0.908), respectively. Conclusion: The developed multiclass semantic segmentation method for intracoronary OCT images demonstrated promising capabilities for various classes, while having included difficult frames, such as those containing artefacts or destabilized plaques. This algorithm is an important step towards comprehensive and standardized OCT image interpretation.

Quantitative analysis of Tumor Microenvironment (TME) provides prognostic and predictive information in several human cancers but, with few exceptions, it is not performed in daily clinical practice since it is extremely time-consuming. We recently showed that the morphology of Tumor Associated Macrophages (TAMs) correlates with outcome in patients with Colo-Rectal Liver Metastases (CLM). However, as for other TME components, recognizing and characterizing hundreds of TAMs in a single histopathological slide is unfeasible. To fasten this process, we explored a deep-learning based solution. We tested three Convolutional Neural Networks (CNNs), namely UNet, SegNet and DeepLab-v3, with three different segmentation strategies, semantic segmentation, pixel penalties and instance segmentation. The different experiments are compared according to the Intersection over Union (IoU), a metric describing the similarity between what CNN predicts as TAM and the ground truth, and the Symmetric Best Dice (SBD), which indicates the ability of CNN to separate different TAMs. UNet and SegNet showed intrinsic limitations in discriminating single TAMs (highest SBD $61.34\pm 2.21$), whereas DeepLab-v3 accurately recognized TAMs from the background (IoU $89.13\pm 3.85$) and separated different TAMs (SBD $79.00\pm 3.72$). This deep-learning pipeline to recognize TAMs in digital slides will allow the characterization of TAM-related metrics in the daily clinical practice, allowing the implementation of prognostic tools.