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Keywords = digital histopathological assessment

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21 pages, 963 KB  
Article
Digital Pathology with AI for Cervical Biopsies: Diagnostic Accuracy at the CIN2+ Threshold
by Anja Kristin Andreassen, Elin Mortensen, Roy Stenbro, Øistein Sørensen and Sveinung Wergeland Sørbye
Cancers 2025, 17(23), 3808; https://doi.org/10.3390/cancers17233808 - 27 Nov 2025
Viewed by 762
Abstract
Background/Objectives: Histopathologic grading of cervical biopsies is subject to interobserver variability, particularly at the CIN2+ treatment threshold. We evaluated a deep learning system (EagleEye) for detecting CIN2+ (CIN2, CIN3, ACIS, invasive carcinoma) on hematoxylin–eosin (H&E) whole-slide images (WSIs) and compared its performance [...] Read more.
Background/Objectives: Histopathologic grading of cervical biopsies is subject to interobserver variability, particularly at the CIN2+ treatment threshold. We evaluated a deep learning system (EagleEye) for detecting CIN2+ (CIN2, CIN3, ACIS, invasive carcinoma) on hematoxylin–eosin (H&E) whole-slide images (WSIs) and compared its performance with independent pathologists, including an AI-assisted workflow. Spatial correspondence with p16 staining was preliminarily assessed. Methods: Ninety-nine archived cervical punch biopsies from a single university hospital, originally diagnosed as Normal (n = 19), CIN1 (n = 20), CIN2 (n = 20), CIN3 (n = 20), or adenocarcinoma in situ (ACIS; n = 20), were digitized in a deliberately spectrum-balanced design. The original sign-out (P1), a second gynecologic pathologist (P2, microscope and digital), EagleEye alone (EE), and an AI-assisted read (EE + P2) served as diagnostic conditions. Outcomes were dichotomized as <CIN2 vs. CIN2+. Agreement was evaluated using Cohen’s κ and sensitivity/specificity (95% CI) under pre-specified internal reference standards. In 30 cases with prior p16 staining, visual correspondence between AI heatmaps/tiles and p16-positive epithelial domains was recorded. Results: Agreement between P1 and EagleEye was moderate (κ = 0.67), while P2 showed high internal consistency (κ = 0.86) and good agreement with P1 (κ = 0.78). Using P1 as reference, EagleEye detected CIN2+ with 93.3% sensitivity and 71.8% specificity. When the AI-assisted consensus (EE + P2) was used as an augmented internal comparator, P1 showed 83.8% sensitivity and 100% specificity, indicating that the human-in-the-loop workflow identified additional CIN2+ cases that had been signed out as <CIN2 by P1, particularly near the CIN1/CIN2 boundary. In a subset of cases originally classified as CIN3 by P1, EagleEye flagged squamous cell carcinoma (SCC); several of these were confirmed as SCC by expert review (EE + P2). In ACIS, EagleEye under-called relative to pathologists but improved after adjudication. p16-to-AI spatial correspondence ≥70% was observed in 73.3% of evaluated cases. Conclusions: In this single-centre, spectrum-balanced cohort, EagleEye achieved high CIN2+ sensitivity and substantial agreement with expert readers in a human-in-the-loop workflow. The main added value was internal case-finding of treatment-relevant lesions when AI assistance was available, while final diagnoses remained with the pathologist. Full article
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18 pages, 1229 KB  
Review
Tumor-Infiltrating Immune Cells in Non-Muscle-Invasive Bladder Cancer: Prognostic Implications, Predictive Value, and Future Perspectives
by Roberta Mazzucchelli, Angelo Cormio, Magda Zanelli, Maurizio Zizzo, Andrea Palicelli, Andrea Benedetto Galosi and Francesca Sanguedolce
Appl. Sci. 2025, 15(22), 12032; https://doi.org/10.3390/app152212032 - 12 Nov 2025
Viewed by 793
Abstract
Non-muscle invasive bladder cancer (NMIBC) accounts for the majority of bladder cancer diagnoses and remains a clinical challenge due to its high recurrence and progression rates despite intravesical Bacillus Calmette–Guérin (BCG) therapy. In recent years, tumor-infiltrating lymphocytes (TILs) have emerged as promising biomarkers, [...] Read more.
Non-muscle invasive bladder cancer (NMIBC) accounts for the majority of bladder cancer diagnoses and remains a clinical challenge due to its high recurrence and progression rates despite intravesical Bacillus Calmette–Guérin (BCG) therapy. In recent years, tumor-infiltrating lymphocytes (TILs) have emerged as promising biomarkers, reflecting the interplay between the tumor and host immune system. However, the evidence regarding their prognostic and predictive role is still conflicting, largely due to methodological heterogeneity, lack of standardized evaluation criteria, and limited prospective validation. This narrative review summarizes the current knowledge on TILs in NMIBC, focusing on their compartmental distribution (stromal, intraepithelial, and tumor–stroma interface), compositional diversity (CD4+, CD8+, Treg, B cells), and spatial dynamics. Special attention is given to their role in predicting response to BCG immunotherapy, the contribution of tumor-associated macrophages and tertiary lymphoid structures, and the emergence of immune escape pathways, including Programmed Death-Ligand 1 (PD-L1) and the HLA-E/NKG2A axis. Advances in digital pathology, spatial transcriptomics, and integrated immunoscore models provide more accurate metrics compared to simple cell counts, highlighting the importance of functional and spatial signatures. Despite encouraging progress, TILs are not yet ready for routine incorporation into histopathological reporting. Future directions include standardized assessment, integration with molecular biomarkers, and prospective multicenter validation to enable their translation into risk stratification and personalized therapeutic decision-making. Full article
(This article belongs to the Section Chemical and Molecular Sciences)
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9 pages, 2067 KB  
Article
Myxoid Glomus Tumors Showing CD34 Expression: A Series of Eight Cases
by Joana Sorino, Mario Della Mura, Anna Colagrande, Costantino Ricci, Giuseppe Ingravallo, Francesco Fanelli, Francesco Fortarezza, Alessio Giubellino and Gerardo Cazzato
Diagnostics 2025, 15(22), 2852; https://doi.org/10.3390/diagnostics15222852 - 11 Nov 2025
Viewed by 483
Abstract
Background: Myxoid glomus tumors (mGTs) are an uncommon histologic pattern of glomus tumors, characterized by prominent myxoid stromal changes that may mimic a wide range of soft tissue neoplasms. Recent reports of unexpected CD34 expression in some cases have further complicated their differential [...] Read more.
Background: Myxoid glomus tumors (mGTs) are an uncommon histologic pattern of glomus tumors, characterized by prominent myxoid stromal changes that may mimic a wide range of soft tissue neoplasms. Recent reports of unexpected CD34 expression in some cases have further complicated their differential diagnosis. Objectives: This study aimed to characterize the histopathological, immunohistochemical, and clinical features of cutaneous mGTs, with particular emphasis on CD34 expression. Methods: We analyzed 8 histologically confirmed cases of cutaneous mGTs underwent to a comprehensive evaluation of morphological features and immunophenotypic profile, with available clinical data. The immunohistochemical panel included smooth muscle actin (SMA), CD34, and S100. Mast cell density was assessed by tryptase in 3 cases. As controls, 8 glomus tumors without myxoid features were also examined for CD34 expression. Results: The cohort consisted of 8 patients (2 males, 6 females; age range 23–71 years). All tumors were located on the distal phalanges of the digits and showed extensive myxoid stromal changes. Immunohistochemistry demonstrated SMA positivity and CD34 expression in all mGTs. In contrast, none of the control GTs without myxoid stroma expressed CD34. Mast cells were consistently identified in the tested cases, predominantly within the myxoid matrix, suggesting a possible role in stromal remodeling. Conclusions: mGTs represent a rare but distinct histological pattern within the glomus tumor spectrum; frequent CD34 expression and mast cell infiltration appear to be characteristic features, although their biological significance remains uncertain. Recognition of these findings is essential to avoid misdiagnosis with other CD34-positive perivascular neoplasms or myxoid soft tissue sarcomas. Full article
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16 pages, 3443 KB  
Article
Automated Detection and Grading of Renal Cell Carcinoma in Histopathological Images via Efficient Attention Transformer Network
by Hissa Al-kuwari, Belqes Alshami, Aisha Al-Khinji, Adnan Haider and Muhammad Arsalan
Med. Sci. 2025, 13(4), 257; https://doi.org/10.3390/medsci13040257 - 1 Nov 2025
Cited by 1 | Viewed by 614
Abstract
Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer [...] Read more.
Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer Network), a dual-stream deep learning model designed to automate and enhance RCC grade classification from histopathological images. Method: EAT-Net integrates EfficientNetB0 for local feature extraction and a Vision Transformer (ViT) stream for capturing global contextual dependencies. The architecture incorporates Squeeze-and-Excitation (SE) modules to recalibrate feature maps, improving focus on informative regions. The model was trained and evaluated on two publicly available datasets, KMC-RENAL and RCCG-Net. Standard preprocessing was applied, and the model’s performance was assessed using accuracy, precision, recall, and F1-score. Results: EAT-Net achieved superior results compared to state-of-the-art models, with an accuracy of 92.25%, precision of 92.15%, recall of 92.12%, and F1-score of 92.25%. Ablation studies demonstrated the complementary value of the EfficientNet and ViT streams. Additionally, Grad-CAM visualizations confirmed that the model focuses on diagnostically relevant areas, supporting its interpretability and clinical relevance. Conclusion: EAT-Net offers an accurate, and explainable framework for RCC grading. Its lightweight architecture and high performance make it well-suited for clinical deployment in digital pathology workflows. Full article
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26 pages, 1421 KB  
Systematic Review
Improving Early Prostate Cancer Detection Through Artificial Intelligence: Evidence from a Systematic Review
by Vincenzo Ciccone, Marina Garofano, Rosaria Del Sorbo, Gabriele Mongelli, Mariella Izzo, Francesco Negri, Roberta Buonocore, Francesca Salerno, Rosario Gnazzo, Gaetano Ungaro and Alessia Bramanti
Cancers 2025, 17(21), 3503; https://doi.org/10.3390/cancers17213503 - 30 Oct 2025
Viewed by 1127
Abstract
Background: Prostate cancer is one of the most common malignancies in men and a leading cause of cancer-related mortality. Early detection is essential to ensure curative treatment and favorable outcomes, but traditional diagnostic approaches—such as serum prostate-specific antigen (PSA) testing, digital rectal examination [...] Read more.
Background: Prostate cancer is one of the most common malignancies in men and a leading cause of cancer-related mortality. Early detection is essential to ensure curative treatment and favorable outcomes, but traditional diagnostic approaches—such as serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE), and histopathological confirmation following biopsy—are limited by suboptimal accuracy and variability. Multiparametric magnetic resonance imaging (mpMRI) has improved diagnostic performance but remains highly dependent on reader expertise. Artificial intelligence (AI) offers promising opportunities to enhance diagnostic accuracy, reproducibility, and efficiency in prostate cancer detection. Objective: To evaluate the diagnostic accuracy and reporting timeliness of AI-based technologies compared with conventional diagnostic methods in the early detection of prostate cancer. Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Cochrane Library were searched for studies published between January 2015 and April 2025. Eligible designs included randomized controlled trials, cohort, case–control, and pilot studies applying AI-based technologies to early prostate cancer diagnosis. Data on AUC-ROC, sensitivity, specificity, predictive values, diagnostic odds ratio (DOR), and time-to-reporting were narratively synthesized due to heterogeneity. Risk of bias was assessed using the QUADAS-AI tool. Results: Twenty-three studies involving 23,270 patients were included. AI-based technologies achieved a median AUC-ROC of 0.88 (range 0.70–0.93), with median sensitivity and specificity of 0.86 and 0.83, respectively. Compared with radiologists, AI or AI-assisted readings improved or matched diagnostic accuracy, reduced inter-reader variability, and decreased reporting time by up to 56%. Conclusions: AI-based technologies show strong diagnostic performance in early prostate cancer detection. However, methodological heterogeneity and limited standardization restrict generalizability. Large-scale prospective trials are required to validate clinical integration. Full article
(This article belongs to the Special Issue Medical Imaging and Artificial Intelligence in Cancer)
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14 pages, 3502 KB  
Article
Deep Learning-Based Nuclei Segmentation and Melanoma Detection in Skin Histopathological Image Using Test Image Augmentation and Ensemble Model
by Mohammadesmaeil Akbarpour, Hamed Fazlollahiaghamalek, Mahdi Barati, Mehrdad Hashemi Kamangar and Mrinal Mandal
J. Imaging 2025, 11(8), 274; https://doi.org/10.3390/jimaging11080274 - 15 Aug 2025
Viewed by 1350
Abstract
Histopathological images play a crucial role in diagnosing skin cancer. However, due to the very large size of digital histopathological images (typically in the order of billion pixels), manual image analysis is tedious and time-consuming. Therefore, there has been significant interest in developing [...] Read more.
Histopathological images play a crucial role in diagnosing skin cancer. However, due to the very large size of digital histopathological images (typically in the order of billion pixels), manual image analysis is tedious and time-consuming. Therefore, there has been significant interest in developing Artificial Intelligence (AI)-enabled computer-aided diagnosis (CAD) techniques for skin cancer detection. Due to the diversity of uncertain cell boundaries, automated nuclei segmentation of histopathological images remains challenging. Automating the identification of abnormal cell nuclei and analyzing their distribution across multiple tissue sections can significantly expedite comprehensive diagnostic assessments. In this paper, a deep neural network (DNN)-based technique is proposed to segment nuclei and detect melanoma in histopathological images. To achieve a robust performance, a test image is first augmented by various geometric operations. The augmented images are then passed through the DNN and the individual outputs are combined to obtain the final nuclei-segmented image. A morphological technique is then applied on the nuclei-segmented image to detect the melanoma region in the image. Experimental results show that the proposed technique can achieve a Dice score of 91.61% and 87.9% for nuclei segmentation and melanoma detection, respectively. Full article
(This article belongs to the Section Medical Imaging)
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21 pages, 2629 KB  
Article
From Pixels to Precision—A Dual-Stream Deep Network for Pathological Nuclei Segmentation
by Rashid Nasimov, Kudratjon Zohirov, Adilbek Dauletov, Akmalbek Abdusalomov and Young Im Cho
Bioengineering 2025, 12(8), 868; https://doi.org/10.3390/bioengineering12080868 - 12 Aug 2025
Viewed by 1246
Abstract
Segmenting cell nuclei in histopathological images is an extremely important process for computational pathology, affecting not only the accuracy of a disease diagnosis but also the analysis of biomarkers and the assessment of cells performed on a large scale. Although many deep learning [...] Read more.
Segmenting cell nuclei in histopathological images is an extremely important process for computational pathology, affecting not only the accuracy of a disease diagnosis but also the analysis of biomarkers and the assessment of cells performed on a large scale. Although many deep learning models can take out global and local features, it is still difficult to find a good balance between semantic context and fine boundary precision, especially when nuclei are overlapping or have changed shapes. In this paper, we put forward a novel deep learning model named Dual-Stream HyperFusionNet (DS-HFN), which is capable of explicitly representing the global contextual and boundary-sensitive features for the robust nuclei segmentation task by first decoupling and then fusing them. The dual-stream encoder in DS-HFN can simultaneously acquire the semantic and edge-focused features, which can be later combined with the help of the attention-driven HyperFeature Embedding Module (HFEM). Additionally, the dual-decoder concept, together with the Gradient-Aligned Loss Function, facilitates structural precision by making the segmentation gradients that are predicted consistent with the ground-truth contours. On various benchmark datasets like TNBC and MoNuSeg, DS-HFN not only achieves better results than other 30 state-of-the-art models in all evaluation metrics but also is less computationally expensive. These findings indicate that DS-HFN provides a capability for accurate nuclei segmentation, which is essential for clinical diagnosis and biomarker analysis, across a wide range of tissues in digital pathology. Full article
(This article belongs to the Special Issue Medical Imaging Analysis: Current and Future Trends)
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21 pages, 1765 KB  
Article
Comparative Diagnostic Efficacy of Four Breast Imaging Modalities in Dense Breasts: A Single-Center Retrospective Study
by Danka Petrović, Bojana Šćepanović, Milena Spirovski, Zoran Nikin and Nataša Prvulović Bunović
Biomedicines 2025, 13(7), 1750; https://doi.org/10.3390/biomedicines13071750 - 17 Jul 2025
Cited by 1 | Viewed by 4328
Abstract
Background and Objectives: The aim of our study was to assess the diagnostic accuracy of four imaging modalities—digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), and breast magnetic resonance imaging (MRI)—applied individually and in combination in early cancer detection in women [...] Read more.
Background and Objectives: The aim of our study was to assess the diagnostic accuracy of four imaging modalities—digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), and breast magnetic resonance imaging (MRI)—applied individually and in combination in early cancer detection in women with dense breasts. Methods: This single-center retrospective study was conducted from January 2021 to September 2024 at the Oncology Institute of Vojvodina in Serbia and included 168 asymptomatic and symptomatic women with dense breasts. Based on the exclusion criteria, the final number of women who were screened with all four imaging methods was 156. The reference standard for checking the diagnostic accuracy of these methods is the result of a histopathological examination, if a biopsy is performed, or a stable radiological finding in the next 12–24 months. Results: The findings underscore the superior diagnostic performance of breast MRI with the highest sensitivity (95.1%), specificity (78.7%), and overall accuracy (87.2%). In contrast, DM showed the lowest sensitivity (87.7%) and low specificity (49.3%). While the combination of DM + DBT + US demonstrated improved sensitivity to 96.3%, its specificity drastically decreased to 32%, illustrating as ensitivity–specificity trade-off. Notably, the integration of all four modalities increased sensitivity to 97.5% but decreased specificity to 29.3%, suggesting an overdiagnosis risk. DBT significantly improved performance over DM alone, likely due to enhanced tissue differentiation. US proved valuable in dense breast tissue but was associated with a high false-positive rate. Breast MRI, even when used alone, confirmed its status as the gold standard for dense breast imaging. However, its widespread use is constrained by economic and logistical barriers. ROC curve analysis further emphasized MRI’s diagnostic superiority (AUC = 0.958) compared with US (0.863), DBT (0.828), and DM (0.820). Conclusions: This study provides a unique, comprehensive comparison of all four imaging modalities within the same patient cohort, offering a rare model for optimizing diagnostic pathways in women with dense breasts. The findings support the strategic integration of complementary imaging approaches to improve early cancer detection while highlighting the risk of increased false-positive rates. In settings where MRI is not readily accessible, a combined DM + DBT + US protocol may serve as a pragmatic alternative, though its limitations in specificity must be carefully considered. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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19 pages, 3064 KB  
Article
HR-pQCT and 3D Printing for Forensic and Orthopaedic Analysis of Gunshot-Induced Bone Damage
by Richard Andreas Lindtner, Lukas Kampik, Werner Schmölz, Mateus Enzenberg, David Putzer, Rohit Arora, Bettina Zelger, Claudia Wöss, Gerald Degenhart, Christian Kremser, Michaela Lackner, Anton Kasper Pallua, Michael Schirmer and Johannes Dominikus Pallua
Biomedicines 2025, 13(7), 1742; https://doi.org/10.3390/biomedicines13071742 - 16 Jul 2025
Viewed by 1152
Abstract
Background/Objectives: Recent breakthroughs in three-dimensional (3D) printing and high-resolution imaging have opened up new possibilities in personalized medicine, surgical planning, and forensic reconstruction. This study breaks new ground by evaluating the integration of high-resolution peripheral quantitative computed tomography (HR-pQCT) with multimodal imaging and [...] Read more.
Background/Objectives: Recent breakthroughs in three-dimensional (3D) printing and high-resolution imaging have opened up new possibilities in personalized medicine, surgical planning, and forensic reconstruction. This study breaks new ground by evaluating the integration of high-resolution peripheral quantitative computed tomography (HR-pQCT) with multimodal imaging and additive manufacturing to assess a chronic, infected gunshot injury in the knee joint of a red deer. This unique approach serves as a translational model for complex skeletal trauma. Methods: Multimodal imaging—including clinical CT, MRI, and HR-pQCT—was used to characterise the extent of osseous and soft tissue damage. Histopathological and molecular analyses were performed to confirm the infectious agent. HR-pQCT datasets were segmented and processed for 3D printing using PolyJet, stereolithography (SLA), and fused deposition modelling (FDM). Printed models were quantitatively benchmarked through 3D surface deviation analysis. Results: Imaging revealed comminuted fractures, cortical and trabecular degradation, and soft tissue involvement, consistent with chronic osteomyelitis. Sphingomonas sp., a bacterium that forms biofilms, was identified as the pathogen. Among the printing methods, PolyJet and SLA demonstrated the highest anatomical accuracy, whereas FDM exhibited greater geometric deviation. Conclusions: HR-pQCT-guided 3D printing provides a powerful tool for the anatomical visualisation and quantitative assessment of complex bone pathology. This approach not only enhances diagnostic precision but also supports applications in surgical rehearsal and forensic analysis. It illustrates the potential of digital imaging and additive manufacturing to advance orthopaedic and trauma care, inspiring future research and applications in the field. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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18 pages, 1680 KB  
Article
Multi-Task Deep Learning for Simultaneous Classification and Segmentation of Cancer Pathologies in Diverse Medical Imaging Modalities
by Maryem Rhanoui, Khaoula Alaoui Belghiti and Mounia Mikram
Onco 2025, 5(3), 34; https://doi.org/10.3390/onco5030034 - 11 Jul 2025
Cited by 1 | Viewed by 4686
Abstract
Background: Clinical imaging is an important part of health care providing physicians with great assistance in patients treatment. In fact, segmentation and grading of tumors can help doctors assess the severity of the cancer at an early stage and increase the chances [...] Read more.
Background: Clinical imaging is an important part of health care providing physicians with great assistance in patients treatment. In fact, segmentation and grading of tumors can help doctors assess the severity of the cancer at an early stage and increase the chances of cure. Despite that Deep Learning for cancer diagnosis has achieved clinically acceptable accuracy, there still remains challenging tasks, especially in the context of insufficient labeled data and the subsequent need for expensive computational ressources. Objective: This paper presents a lightweight classification and segmentation deep learning model to assist in the identification of cancerous tumors with high accuracy despite the scarcity of medical data. Methods: We propose a multi-task architecture for classification and segmentation of cancerous tumors in the Brain, Skin, Prostate and lungs. The model is based on the UNet architecture with different pre-trained deep learning models (VGG 16 and MobileNetv2) as a backbone. The multi-task model is validated on relatively small datasets (slightly exceed 1200 images) that are diverse in terms of modalities (IRM, X-Ray, Dermoscopic and Digital Histopathology), number of classes, shapes, and sizes of cancer pathologies using the accuracy and dice coefficient as statistical metrics. Results: Experiments show that the multi-task approach improve the learning efficiency and the prediction accuracy for the segmentation and classification tasks, compared to training the individual models separately. The multi-task architecture reached a classification accuracy of 86%, 90%, 88%, and 87% respectively for Skin Lesion, Brain Tumor, Prostate Cancer and Pneumothorax. For the segmentation tasks we were able to achieve high precisions respectively 95%, 98% for the Skin Lesion and Brain Tumor segmentation and a 99% precise segmentation for both Prostate cancer and Pneumothorax. Proving that the multi-task solution is more efficient than single-task networks. Full article
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16 pages, 1312 KB  
Article
Detection Rates of Prostate Cancer Across Prostatic Zones Using Freehand Single-Access Transperineal Fusion Biopsies
by Filippo Carletti, Giuseppe Reitano, Eleonora Martina Toffoletto, Arianna Tumminello, Elisa Tonet, Giovanni Basso, Martina Bruniera, Anna Cacco, Elena Rebaudengo, Giorgio Saggionetto, Giovanni Betto, Giacomo Novara, Fabrizio Dal Moro and Fabio Zattoni
Cancers 2025, 17(13), 2206; https://doi.org/10.3390/cancers17132206 - 30 Jun 2025
Cited by 2 | Viewed by 899
Abstract
Background/Objectives: It remains unclear whether certain areas of the prostate are more difficult to accurately sample using MRI/US-fusion-guided freehand single-access transperineal prostate biopsy (FSA-TP). The aim of this study was to evaluate the detection rates of clinically significant (cs) and clinically insignificant [...] Read more.
Background/Objectives: It remains unclear whether certain areas of the prostate are more difficult to accurately sample using MRI/US-fusion-guided freehand single-access transperineal prostate biopsy (FSA-TP). The aim of this study was to evaluate the detection rates of clinically significant (cs) and clinically insignificant (ci) prostate cancer (PCa) in each prostate zone during FSA-TP MRI-target biopsies (MRI-TBs) and systematic biopsies (SB). Methods: This monocentric observational study included a cohort of 277 patients with no prior history of PCa who underwent 3 MRI-TB cores and 14 SB cores with an FSA-TP from January to December 2023. The intraclass correlation coefficient (ICC) was assessed to evaluate the correlation between the Prostate Imaging–Reporting and Data System (PI-RADS) of the index lesion and the International Society of Urological Pathology (ISUP) grade stratified according to prostate zone and region of index lesion at MRI. Multivariate logistic regression analysis was conducted to identify factors associated with PCa and csPCa in patients with discordant results between MRI-TB and SB. Results: FSA-TP-MRI-TB demonstrated higher detection rates of both ciPCa and csPCa in the anterior, apical, and intermediate zones when each of the three MRI-TB cores was analysed separately (p < 0.01). However, when all MRI-TB cores were combined, no significant differences were observed in detection rates across prostate zones (apex, mid, base; p = 0.57) or regions (anterior vs. posterior; p = 0.34). Concordance between radiologic and histopathologic findings, as measured by the intraclass correlation coefficient (ICC), was similar across all zones (apex ICC: 0.33; mid ICC: 0.34; base ICC: 0.38) and regions (anterior ICC: 0.42; posterior ICC: 0.26). Univariate analysis showed that in patients with PCa detected on SB but with negative MRI-TB, older age was the only significant predictor (p = 0.04). Multivariate analysis revealed that patients with PCa detected on MRI-TB but with negative SB, only PSA remained a significant predictor (OR 1.2, 95% CI 1.1–1.4; p = 0.01). In cases with csPCa detected on MRI-TB but with negative SB, age (OR: 1.0, 95% CI 1.0–1.1; p = 0.02), positive digital rectal examination (OR: 2.0, 95% CI 1.1–3.8; p = 0.03), PI-RADS score >3 (OR: 4.5, 95% CI 1.7–12.1; p < 0.01), and larger lesion size (OR: 1.1, 95% CI 1.1–1.2; p < 0.01) were significant predictors. Conclusions: FSA-TP using 14 SB cores and 3 MRI-TB cores ensures comprehensive sampling of all prostate regions, including anterior and apical zones, without significant differences in detection rates between nodules across different zones. Only in a small percentage of patients was csPCa detected exclusively by SB, highlighting the small but important complementary value of combining SB and MRI-TB. Full article
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14 pages, 354 KB  
Article
An Exploration of Discrepant Recalls Between AI and Human Readers of Malignant Lesions in Digital Mammography Screening
by Suzanne L. van Winkel, Ioannis Sechopoulos, Alejandro Rodríguez-Ruiz, Wouter J. H. Veldkamp, Gisella Gennaro, Margarita Chevalier, Thomas H. Helbich, Tianyu Zhang, Matthew G. Wallis and Ritse M. Mann
Diagnostics 2025, 15(12), 1566; https://doi.org/10.3390/diagnostics15121566 - 19 Jun 2025
Cited by 1 | Viewed by 1534
Abstract
Background: The integration of artificial intelligence (AI) in digital mammography (DM) screening holds promise for early breast cancer detection, potentially enhancing accuracy and efficiency. However, AI performance is not identical to that of human observers. We aimed to identify common morphological image characteristics [...] Read more.
Background: The integration of artificial intelligence (AI) in digital mammography (DM) screening holds promise for early breast cancer detection, potentially enhancing accuracy and efficiency. However, AI performance is not identical to that of human observers. We aimed to identify common morphological image characteristics of true cancers that are missed by either AI or human screening when their interpretations are discrepant. Methods: Twenty-six breast cancer-positive cases, identified from a large retrospective multi-institutional digital mammography dataset based on discrepant AI and human interpretations, were included in a reader study. Ground truth was confirmed by histopathology or ≥1-year follow-up. Fourteen radiologists assessed lesion visibility, morphological features, and likelihood of malignancy. AI performance was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). The reader study results were analyzed using interobserver agreement measures and descriptive statistics. Results: AI demonstrated high discriminative capability in the full dataset, with AUCs ranging from 0.903 (95% CI: 0.862–0.944) to 0.946 (95% CI: 0.896–0.996). Cancers missed by AI had a significantly smaller median size (9.0 mm, IQR 6.5–12.0) compared to those missed by human readers (21.0 mm, IQR 10.5–41.0) (p = 0.0014). Cancers in discrepant cases were often described as having ‘low visibility’, ‘indistinct margins’, or ‘irregular shape’. Calcifications were observed in 27% of human-missed cancers (42/154) versus 18% of AI-missed cancers (38/210). A very high likelihood of malignancy was assigned in 32.5% (50/154) of human-missed cancers compared to 19.5% (41/210) of AI-missed cancers. Overall inter-rater agreement was poor to fair (<0.40), indicating interpretation challenges of the selected images. Among the human-missed cancers, calcifications were more frequent (42/154; 27%) than among the AI-missed cancers (38/210; 18%) (p = 0.396). Furthermore, 50/154 (32.5%) human-missed cancers were deemed to have a very high likelihood of malignancy, compared to 41/210 (19.5%) AI-missed cancers (p = 0.8). Overall inter-rater agreement on the items assessed during the reader study was poor to fair (<0.40), suggesting that interpretation of the selected images was challenging. Conclusions: Lesions missed by AI were smaller and less often calcified than cancers missed by human readers. Cancers missed by AI tended to show lower levels of suspicion than those missed by human readers. While definitive conclusions are premature, the findings highlight the complementary roles of AI and human readers in mammographic interpretation. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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16 pages, 2065 KB  
Article
An Information-Extreme Algorithm for Universal Nuclear Feature-Driven Automated Classification of Breast Cancer Cells
by Taras Savchenko, Ruslana Lakhtaryna, Anastasiia Denysenko, Anatoliy Dovbysh, Sarah E. Coupland and Roman Moskalenko
Diagnostics 2025, 15(11), 1389; https://doi.org/10.3390/diagnostics15111389 - 30 May 2025
Viewed by 1060
Abstract
Background/Objectives: Breast cancer diagnosis heavily relies on histopathological assessment, which is prone to subjectivity and inefficiency, especially with whole-slide imaging (WSI). This study addressed these limitations by developing an automated breast cancer cell classification algorithm using an information-extreme machine learning approach and universal [...] Read more.
Background/Objectives: Breast cancer diagnosis heavily relies on histopathological assessment, which is prone to subjectivity and inefficiency, especially with whole-slide imaging (WSI). This study addressed these limitations by developing an automated breast cancer cell classification algorithm using an information-extreme machine learning approach and universal cytological features, aiming for objective and generalized histopathological diagnosis. Methods: Digitized histological images were processed to identify hyperchromatic cells. A set of 21 cytological features (10 geometric and 11 textural), chosen for their potential universality across cancers, were extracted from individual cells. These features were then used to classify cells as normal or malignant using an information-extreme algorithm. This algorithm optimizes an information criterion within a binary Hamming space to achieve robust recognition with minimal input features. The architectural innovation lies in the application of this information-extreme approach to cytological feature analysis for cancer cell classification. Results: The algorithm’s functional efficiency was evaluated on a dataset of 176 labeled cell images, yielding promising results: an accuracy of 89%, a precision of 85%, a recall of 84%, and an F1-score of 88%. These metrics demonstrate a balanced and effective model for automated breast cancer cell classification. Conclusions: The proposed information-extreme algorithm utilizing universal cytological features offers a potentially objective and computationally efficient alternative to traditional methods and may mitigate some limitations of deep learning in histopathological analysis. Future work will focus on validating the algorithm on larger datasets and exploring its applicability to other cancer types. Full article
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15 pages, 2410 KB  
Article
Multiple Instance Learning for the Detection of Lymph Node and Omental Metastases in Carcinoma of the Ovaries, Fallopian Tubes and Peritoneum
by Katie E. Allen, Jack Breen, Geoff Hall, Georgia Mappa, Kieran Zucker, Nishant Ravikumar and Nicolas M. Orsi
Cancers 2025, 17(11), 1789; https://doi.org/10.3390/cancers17111789 - 27 May 2025
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Abstract
Background/Objectives: Surgical pathology of tubo-ovarian and peritoneal cancer carries a well-recognised diagnostic workload, partly due to the large amount of non-primary tumour-related tissue requiring assessment for the presence of metastatic disease. The lymph nodes and omentum are almost universally included in such [...] Read more.
Background/Objectives: Surgical pathology of tubo-ovarian and peritoneal cancer carries a well-recognised diagnostic workload, partly due to the large amount of non-primary tumour-related tissue requiring assessment for the presence of metastatic disease. The lymph nodes and omentum are almost universally included in such resection cases and contribute considerably to this burden, principally due to volume rather than task complexity. To date, artificial intelligence (AI)-based studies have reported good success rates in identifying nodal spread in other malignancies, but the development of such time-saving assistive digital solutions has been neglected in ovarian cancer. This study aimed to detect the presence or absence of metastatic ovarian carcinoma in the lymph nodes and omentum. Methods: We used attention-based multiple-instance learning (ABMIL) with a vision-transformer foundation model to classify whole-slide images (WSIs) as either containing ovarian carcinoma metastases or not. Training and validation were conducted with a total of 855 WSIs of surgical resection specimens collected from 404 patients at Leeds Teaching Hospitals NHS Trust. Results: Ensembled classification from hold-out testing reached an AUROC of 0.998 (0.985–1.0) and a balanced accuracy of 100% (100.0–100.0%) in the lymph node set, and an AUROC of 0.963 (0.911–0.999) and a balanced accuracy of 98.0% (94.8–100.0%) in the omentum set. Conclusions: This model shows great potential in the identification of ovarian carcinoma nodal and omental metastases, and could provide clinical utility through its ability to pre-screen WSIs prior to histopathologist review. In turn, this could offer significant time-saving benefits and streamline clinical diagnostic workflows, helping to address the chronic staffing shortages in histopathology. Full article
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19 pages, 5211 KB  
Article
Alterations in the Temporal Variation and Spatial Distribution of Blood–Brain Barrier Permeability Following Electromagnetic Pulse Radiation: A Study Based on Dynamic Contrast-Enhanced MRI
by Kexian Wang, Haoyu Wang, Ji Dong, Li Zhao, Hui Wang, Jing Zhang, Xinping Xu, Binwei Yao, Yunfei Lai and Ruiyun Peng
Brain Sci. 2025, 15(6), 577; https://doi.org/10.3390/brainsci15060577 - 27 May 2025
Viewed by 1109
Abstract
Background: Previous studies have suggested that electromagnetic pulse (EMP) can induce openings in the blood–brain barrier (BBB). However, the temporal variation and spatial distribution of BBB permeability after EMP radiation are difficult to assess using conventional histopathological approaches. Dynamic contrast-enhanced magnetic resonance imaging [...] Read more.
Background: Previous studies have suggested that electromagnetic pulse (EMP) can induce openings in the blood–brain barrier (BBB). However, the temporal variation and spatial distribution of BBB permeability after EMP radiation are difficult to assess using conventional histopathological approaches. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a valuable tool for the in vivo evaluation of BBB permeability. The main purpose of this study was to investigate the temporal variation and spatial distribution of BBB permeability after EMP radiation in rats using DCE-MRI. Methods: The dose of EMP was estimated through simulations utilizing a digital rat model comprising 16 distinct brain regions. Then, the changes in BBB permeability of the different rat brain regions at different time points (3 h and 24 h) after EMP radiation were evaluated using quantitative DCE-MRI. Furthermore, the spatial difference in BBB permeability was assessed 3 h after exposure. Finally, the dose–effect relationship between the electric field strength and the BBB permeability was also investigated. Results: The results demonstrated that the changes in the values of volume transfer constant (ΔKtrans) significantly increased in several rat brain regions at 3 h after 400 kV/m EMP radiation. These changes vanished 24 h after exposure. Meanwhile, no significant spatial differences in BBB permeability were observed after EMP radiation. Moreover, Pearson’s correlation analysis showed that there was a significant positive linear relationship between BBB permeability and the electric field strength within an external electric field strength range of 0 to 400 kV/m at 3 h after EMP radiation. Conclusions: EMP radiation can induce a reversible increase in BBB permeability in rats. Moreover, no significant differences in BBB permeability were found across different brain regions. Additionally, the degree of BBB permeability was positively correlated with the regional electric field strength of EMP radiation within an external electric field strength range of 0 to 400 kV/m at 3 h after EMP radiation. These results indicate the promising potential of employing EMP for transient openings in the BBB, which could facilitate clinical pharmacological interventions via drug delivery into the brain. Full article
(This article belongs to the Special Issue Application of MRI in Brain Diseases)
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