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Abstract Background The tumor microenvironment (TME) plays a key role in lung cancer initiation, proliferation, invasion, and metastasis. Artificial intelligence (AI) methods could potentially accelerate TME analysis. The aims of this study were to (1) assess the feasibility of using hematoxylin and eosin (H&E)-stained whole slide images (WSI) to develop an AI model for evaluating the TME and (2) to characterize the TME of adenocarcinoma (ADCA) and squamous cell carcinoma (SCCA) in fibrotic and non-fibrotic lung. Methods The cohort was derived from chest CT scans of patients presenting with lung neoplasms, with and without background fibrosis. WSI images were generated from slides of all 76 available pathology cases with ADCA (n = 53) or SCCA (n = 23) in fibrotic (n = 47) or non-fibrotic (n = 29) lung. Detailed ground-truth annotations, including of stroma (i.e., fibrosis, vessels, inflammation), necrosis and background, were performed on WSI and optimized via an expert-in-the-loop (EITL) iterative procedure using a lightweight [random forest (RF)] classifier. A convolution neural network (CNN)-based model was used to achieve tissue-level multiclass segmentation. The model was trained on 25 annotated WSI from 13 cases of ADCA and SCCA within and without fibrosis and then applied to the 76-case cohort. The TME analysis included tumor stroma ratio (TSR), tumor fibrosis ratio (TFR), tumor inflammation ratio (TIR), tumor vessel ratio (TVR), tumor necrosis ratio (TNR), and tumor background ratio (TBR). Results The model’s overall classification for precision, sensitivity, and F1-score were 94%, 90%, and 91%, respectively. Statistically significant differences were noted in TSR (p = 0.041) and TFR (p = 0.001) between fibrotic and non-fibrotic ADCA. Within fibrotic lung, statistically significant differences were present in TFR (p = 0.039), TIR (p = 0.003), TVR (p = 0.041), TNR (p = 0.0003), and TBR (p = 0.020) between ADCA and SCCA. Conclusion The combined EITL—RF CNN model using only H&E WSI can facilitate multiclass evaluation and quantification of the TME. There are significant differences in the TME of ADCA and SCCA present within or without background fibrosis. Future studies are needed to determine the significance of TME on prognosis and treatment.

Abstract Sustained injury from factors such as hypoxia, infection, or physical damage may provoke improper tissue repair and the anomalous deposition of connective tissue that causes fibrosis. This phenomenon may take place in any organ, ultimately leading to their dysfunction and eventual failure. Tissue fibrosis has also been found to be central in both the process of carcinogenesis and cancer progression. Thus, its prompt diagnosis and regular monitoring is necessary for implementing effective disease-modifying interventions aiming to reduce mortality and improve overall quality of life. While significant research has been conducted on these subjects, a comprehensive understanding of how their relationship manifests through modern imaging techniques remains to be established. This work intends to provide a comprehensive overview of imaging technologies relevant to the detection of fibrosis affecting thoracic organs as well as to explore potential future advancements in this field.

Abstract Fibrosis is a pathological process involving the abnormal deposition of connective tissue, resulting from improper tissue repair in response to sustained injury caused by hypoxia, infection, or physical damage. It can impact any organ, leading to their dysfunction and eventual failure. Additionally, tissue fibrosis plays an important role in carcinogenesis and the progression of cancer. Early and accurate diagnosis of organ fibrosis, coupled with regular surveillance, is essential for timely disease-modifying interventions, ultimately reducing mortality and enhancing quality of life. While extensive research has already been carried out on the topics of aberrant wound healing and fibrogenesis, we lack a thorough understanding of how their relationship reveals itself through modern imaging techniques. This paper focuses on fibrosis of the genito-urinary system, detailing relevant imaging technologies used for its detection and exploring future directions.

Abstract Fibrosis is the aberrant process of connective tissue deposition from abnormal tissue repair in response to sustained tissue injury caused by hypoxia, infection, or physical damage. It can affect almost all organs in the body causing dysfunction and ultimate organ failure. Tissue fibrosis also plays a vital role in carcinogenesis and cancer progression. The early and accurate diagnosis of organ fibrosis along with adequate surveillance are helpful to implement early disease-modifying interventions, important to reduce mortality and improve quality of life. While extensive research has already been carried out on the topic, a thorough understanding of how this relationship reveals itself using modern imaging techniques has yet to be established. This work outlines the ways in which fibrosis shows up in abdominal organs and has listed the most relevant imaging technologies employed for its detection. New imaging technologies and developments are discussed along with their promising applications in the early detection of organ fibrosis.

Abstract Over the last five decades, breast density has been associated with increased risk of developing breast cancer. Mammographically dense breasts are considered those belonging to the heterogeneously dense breasts, and extremely dense breasts subgroups according to the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS). There is a statistically significant correlation between the increased mammographic density and the presence of more glandular tissue alone. However, the strength of this correlation is weak. Although the mechanisms driving breast density-related tumor initiation and progression are still unknown, there is evidence suggesting that certain molecular pathways participating in epithelial-stromal interactions may play a pivotal role in the deposition of fibrillar collagen, increased matrix stiffness, and cell migration that favor breast density and carcinogenesis. This article describes these molecular mechanisms as potential “landscapers” for breast density-related cancer. We also introduce the term “Breast Compactness” to reflect collagen density of breast tissue on chest CT scan and the use of breast stiffness measurements as imaging biomarkers for breast cancer screening and risk stratification.

Abstract The periphery of malignant tumors and the leading edge of fibrotic tissue have analogous metabolic pathways. Both use glycolysis as the primary source of energy to produce biomass with consequential acidification of the microenvironment. A low PH has been shown to increase the ability of cancer cells to invade the surrounding tissue in both in vitro and in vivo studies. The pH-dependent activation of TGF-B leading to myofibroblast activation is an important step in the initiation and progression of fibrosis. Markers of accelerated cell proliferation have also been reported in the periphery of malignant tumors and the leading edge of fibrosis. Understanding the shared molecular and metabolic characteristics of these conditions may explain the increased prevalence of cancer among patients with fibrosis.