Characterization of a Delivery System Based on a Hyaluronic Acid 3D Scaffold and Gelatin Microparticles.

The objective of this study was to develop and characterize a novel hyaluronic acid (HA) 3D scaffold integrated with gelatin microparticles for sustained-delivery applications. To achieve this goal, the delivery microparticles were synthesized and thoroughly characterized, focusing on their crosslinking mechanisms (vanillin and genipin), degradation profiles, and release kinetics. Additionally, the cytotoxicity of the system was assessed, and its impact on the cell adhesion and distribution using mouse fibroblasts was examined. The combination of both biomaterials offers a novel platform for the gradual release of various factors encapsulated within the microparticles while simultaneously providing cell protection, support, and controlled factor dispersion due to the HA 3D scaffold matrix. Hence, this system offers a platform for addressing injure repair by continuously releasing specific encapsulated factors for optimal tissue regeneration. Additionally, by leveraging the properties of HA conjugates with small drug molecules, we can enhance the solubility, targeting capabilities, and cellular absorption, as well as prolong the system stability and half-life. As a result, this integrated approach presents a versatile strategy for therapeutic interventions aimed at promoting tissue repair and regeneration.

Artificial Intelligence for breast cancer detection: Technology, challenges, and prospects.

PURPOSE: This review provides an overview of the current state of artificial intelligence (AI) technology for automated detection of breast cancer in digital mammography (DM) and digital breast tomosynthesis (DBT). It aims to discuss the technology, available AI systems, and the challenges faced by AI in breast cancer screening. METHODS: The review examines the development of AI technology in breast cancer detection, focusing on deep learning (DL) techniques and their differences from traditional computer-aided detection (CAD) systems. It discusses data pre-processing, learning paradigms, and the need for independent validation approaches. RESULTS: DL-based AI systems have shown significant improvements in breast cancer detection. They have the potential to enhance screening outcomes, reduce false negatives and positives, and detect subtle abnormalities missed by human observers. However, challenges like the lack of standardised datasets, potential bias in training data, and regulatory approval hinder their widespread adoption. CONCLUSIONS: AI technology has the potential to improve breast cancer screening by increasing accuracy and reducing radiologist workload. DL-based AI systems show promise in enhancing detection performance and eliminating variability among observers. Standardised guidelines and trustworthy AI practices are necessary to ensure fairness, traceability, and robustness. Further research and validation are needed to establish clinical trust in AI. Collaboration between researchers, clinicians, and regulatory bodies is crucial to address challenges and promote AI implementation in breast cancer screening.

Multi-vendor robustness analysis of a commercial artificial intelligence system for breast cancer detection.

Purpose: Population-based screening programs for the early detection of breast cancer have significantly reduced mortality in women, but they are resource intensive in terms of time, cost, and workload and still have limitations mainly due to the use of 2D imaging techniques, which may cause overlapping of tissues, and interobserver variability. Artificial intelligence (AI) systems may be a valuable tool to assist radiologist when reading and classifying mammograms based on the malignancy of the detected lesions. However, there are several factors that can influence the outcome of a mammogram and thus also the detection capability of an AI system. The aim of our work is to analyze the robustness of the diagnostic ability of an AI system designed for breast cancer detection. Approach: Mammograms from a population-based screening program were scored with the AI system. The sensitivity and specificity by means of the area under the receiver operating characteristic (ROC) curve were obtained as a function of the mammography unit manufacturer, demographic characteristics, and several factors that may affect the image quality (age, breast thickness and density, compression applied, beam quality, and delivered dose). Results: The area under the curve (AUC) from the scoring ROC curve was 0.92 (95% confidence interval = 0.89 - 0.95). It showed no dependence with any of the parameters considered, as the differences in the AUC for different interval values were not statistically significant. Conclusion: The results suggest that the AI system analyzed in our work has a robust diagnostic capability, and that its accuracy is independent of the studied parameters.

Multi-modal artificial intelligence for the combination of automated 3D breast ultrasound and mammograms in a population of women with predominantly dense breasts.

OBJECTIVES: To assess the stand-alone and combined performance of artificial intelligence (AI) detection systems for digital mammography (DM) and automated 3D breast ultrasound (ABUS) in detecting breast cancer in women with dense breasts. METHODS: 430 paired cases of DM and ABUS examinations from a Asian population with dense breasts were retrospectively collected. All cases were analyzed by two AI systems, one for DM exams and one for ABUS exams. A selected subset (n = 152) was read by four radiologists. The performance of AI systems was based on analysis of the area under the receiver operating characteristic curve (AUC). The maximum Youden's index and its associated sensitivity and specificity were also reported for each AI systems. Detection performance of human readers in the subcohort of the reader study was measured in terms of sensitivity and specificity. RESULTS: The performance of the AI systems in a multi-modal setting was significantly better when the weights of AI-DM and AI-ABUS were 0.25 and 0.75, respectively, than each system individually in a single-modal setting (AUC-AI-Multimodal = 0.865; AUC-AI-DM = 0.832, p = 0.026; AUC-AI-ABUS = 0.841, p = 0.041). The maximum Youden's index for AI-Multimodal was 0.707 (sensitivity = 79.4%, specificity = 91.2%). In the subcohort that underwent human reading, the panel of four readers achieved a sensitivity of 93.2% and specificity of 32.7%. AI-multimodal achieves superior or equal sensitivity as single human readers at the same specificity operating points on the ROC curve. CONCLUSION: Multimodal (ABUS + DM) AI systems for detecting breast cancer in women with dense breasts are a potential solution for breast screening in radiologist-scarce regions.

Patient-derived heterogeneous breast phantoms for advanced dosimetry in mammography and tomosynthesis.

BACKGROUND: Understanding the magnitude and variability of the radiation dose absorbed by the breast fibroglandular tissue during mammography and digital breast tomosynthesis (DBT) is of paramount importance to assess risks versus benefits. Although homogeneous breast models have been proposed and used for decades for this purpose, they do not accurately reflect the actual heterogeneous distribution of the fibroglandular tissue in the breast, leading to biases in the estimation of dose from these modalities. PURPOSE: To develop and validate a method to generate patient-derived, heterogeneous digital breast phantoms for breast dosimetry in mammography and DBT. METHODS: The proposed phantoms were developed starting from patient-based models of compressed breasts, generated for multiple thicknesses and representing the two standard views acquired in mammography and DBT, that is, cranio-caudal (CC) and medio-lateral-oblique (MLO). Internally, the breast phantoms were defined as consisting of an adipose/fibroglandular tissue mixture, with a nonspatially uniform relative concentration. The parenchyma distributions were obtained from a previously described model based on patient breast computed tomography data that underwent simulated compression. Following these distributions, phantoms with any glandular fraction (1%-100%) and breast thickness (12-125 mm) can be generated, for both views. The phantoms were validated, in terms of their accuracy for average normalized glandular dose (Dg N) estimation across samples of patient breasts, using 88 patient-specific phantoms involving actual patient distribution of the fibroglandular tissue in the breast, and compared to that obtained using a homogeneous model similar to those currently used for breast dosimetry. RESULTS: The average Dg N estimated for the proposed phantoms was concordant with that absorbed by the patient-specific phantoms to within 5% (CC) and 4% (MLO). These Dg N estimates were over 30% lower than those estimated with the homogeneous models, which overestimated the average Dg N by 43% (CC), and 32% (MLO) compared to the patient-specific phantoms. CONCLUSIONS: The developed phantoms can be used for dosimetry simulations to improve the accuracy of dose estimates in mammography and DBT.

An Artificial Intelligence-based Mammography Screening Protocol for Breast Cancer: Outcome and Radiologist Workload.

Background Developments in artificial intelligence (AI) systems to assist radiologists in reading mammograms could improve breast cancer screening efficiency. Purpose To investigate whether an AI system could detect normal, moderate-risk, and suspicious mammograms in a screening sample to safely reduce radiologist workload and evaluate across Breast Imaging Reporting and Data System (BI-RADS) densities. Materials and Methods This retrospective simulation study analyzed mammographic examination data consecutively collected from January 2014 to December 2015 in the Danish Capital Region breast cancer screening program. All mammograms were scored from 0 to 10, representing the risk of malignancy, using an AI tool. During simulation, normal mammograms (score < 5) would be excluded from radiologist reading and suspicious mammograms (score > recall threshold [RT]) would be recalled. Two radiologists read the remaining mammograms. The RT was fitted using another independent cohort (same institution) by matching to the radiologist sensitivity. This protocol was further applied to each BI-RADS density. Screening outcomes were measured using the sensitivity, specificity, workload, and false-positive rate. The AI-based screening was tested for noninferiority sensitivity compared with radiologist screening using the Farrington-Manning test. Specificities were compared using the McNemar test. Results The study sample comprised 114 421 screenings for breast cancer in 114 421 women, resulting in 791 screen-detected, 327 interval, and 1473 long-term cancers and 2107 false-positive screenings. The mean age of the women was 59 years ± 6 (SD). The AI-based screening sensitivity was 69.7% (779 of 1118; 95% CI: 66.9, 72.4) and was noninferior (P = .02) to the radiologist screening sensitivity of 70.8% (791 of 1118; 95% CI: 68.0, 73.5). The AI-based screening specificity was 98.6% (111 725 of 113 303; 95% CI: 98.5, 98.7), which was higher (P < .001) than the radiologist specificity of 98.1% (111 196 of 113 303; 95% CI: 98.1, 98.2). The radiologist workload was reduced by 62.6% (71 585 of 114 421), and 25.1% (529 of 2107) of false-positive screenings were avoided. Screening results were consistent across BI-RADS densities, although not significantly so for sensitivity. Conclusion Artificial intelligence (AI)-based screening could detect normal, moderate-risk, and suspicious mammograms in a breast cancer screening program, which may reduce the radiologist workload. AI-based screening performed consistently across breast densities. © RSNA, 2022 Online supplemental material is available for this article.

Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization.

OBJECTIVES: To study the mechanism by which the readthrough mutation in TNFRSF11B, encoding osteoprotegerin (OPG) with additional 19 amino acids at its C-terminus (OPG-XL), causes the characteristic bidirectional phenotype of subchondral bone turnover accompanied by cartilage mineralization in chondrocalcinosis patients. METHODS: OPG-XL was studied by human induced pluripotent stem cells expressing OPG-XL and two isogenic CRISPR/Cas9-corrected controls in cartilage and bone organoids. Osteoclastogenesis was studied with monocytes from OPG-XL carriers and matched healthy controls followed by gene expression characterization. Dual energy X-ray absorptiometry scans and MRI analyses were used to characterize the phenotype of carriers and non-carriers of the mutation. RESULTS: Human OPG-XL carriers relative to sex- and age-matched controls showed, after an initial delay, large active osteoclasts with high number of nuclei. By employing hiPSCs expressing OPG-XL and isogenic CRISPR/Cas9-corrected controls to established cartilage and bone organoids, we demonstrated that expression of OPG-XL resulted in excessive fibrosis in cartilage and high mineralization in bone accompanied by marked downregulation of MGP, encoding matrix Gla protein, and upregulation of DIO2, encoding type 2 deiodinase, gene expression, respectively. CONCLUSIONS: The readthrough mutation at CCAL1 locus in TNFRSF11B identifies an unknown role for OPG-XL in subchondral bone turnover and cartilage mineralization in humans via DIO2 and MGP functions. Previously, OPG-XL was shown to affect binding between RANKL and heparan sulphate (HS) resulting in loss of immobilized OPG-XL. Therefore, effects may be triggered by deficiency in the immobilization of OPG-XL Since the characteristic bidirectional pathophysiology of articular cartilage calcification accompanied by low subchondral bone mineralization is also a hallmark of OA pathophysiology, our results are likely extrapolated to common arthropathies.

Interval Cancer Detection Using a Neural Network and Breast Density in Women with Negative Screening Mammograms.

Background Inclusion of mammographic breast density (BD) in breast cancer risk models improves accuracy, but accuracy remains modest. Interval cancer (IC) risk prediction may be improved by combining assessments of BD and an artificial intelligence (AI) cancer detection system. Purpose To evaluate the performance of a neural network (NN)-based model that combines the assessments of BD and an AI system in the prediction of risk of developing IC among women with negative screening mammography results. Materials and Methods This retrospective nested case-control study performed with screening examinations included women who developed IC and women with normal follow-up findings (from January 2011 to January 2015). An AI cancer detection system analyzed all studies yielding a score of 1-10, representing increasing likelihood of malignancy. BD was automatically computed using publicly available software. An NN model was trained by combining the AI score and BD using 10-fold cross-validation. Bootstrap analysis was used to calculate the area under the receiver operating characteristic curve (AUC), sensitivity at 90% specificity, and 95% CIs of the AI, BD, and NN models. Results A total of 2222 women with IC and 4661 women in the control group were included (mean age, 61 years; age range, 49-76 years). AUC of the NN model was 0.79 (95% CI: 0.77,0.81), which was higher than AUC of the AI cancer detection system or BD alone (AUC, 0.73 [95% CI: 0.71, 0.76] and 0.69 [95% CI: 0.67, 0.71], respectively; P < .001 for both). At 90% specificity, the NN model had a sensitivity of 50.9% (339 of 666 women; 95% CI: 45.2, 56.3) for prediction of IC, which was higher than that of the AI system (37.5%; 250 of 666 women; 95% CI: 33.0, 43.7; P < .001) or BD percentage alone (22.4%; 149 of 666 women; 95% CI: 17.9, 28.5; P < .001). Conclusion The combined assessment of an artificial intelligence detection system and breast density measurements enabled identification of a larger proportion of women who would develop interval cancer compared with either method alone. Published under a CC BY 4.0 license.

The role of TNFRSF11B in development of osteoarthritic cartilage.

OBJECTIVES: OA is a complex genetic disease with different risk factors contributing to its development. One of the genes, TNFRSF11B, previously identified with gain-of-function mutation in a family with early-onset OA with chondrocalcinosis, is among the highest upregulated genes in lesioned OA cartilage (RAAK-study). Here, we determined the role of TNFRSF11B overexpression in development of OA. METHODS: Human primary articular chondrocytes (9 donors RAAK study) were transduced using lentiviral particles with or without TNFRSF11B. Cells were cultured for 1 week in a 3 D in-vitro chondrogenic model. TNFRSF11B overexpression was confirmed by RT-qPCR, immunohistochemistry and ELISA. Effects of TNFRSF11B overexpression on cartilage matrix deposition, matrix mineralization, and genes highly correlated to TNFRSF11B in RNA-sequencing dataset (r >0.75) were determined by RT-qPCR. Additionally, glycosaminoglycans and collagen deposition were visualized with Alcian blue staining and immunohistochemistry (COL1 and COL2). RESULTS: Overexpression of TNFRSF11B resulted in strong upregulation of MMP13, COL2A1 and COL1A1. Likewise, mineralization and osteoblast characteristic markers RUNX2, ASPN and OGN showed a consistent increase. Among 30 genes highly correlated to TNFRSF11B, expression of only eight changed significantly, with BMP6 showing the highest increase (9-fold) while expression of RANK and RANKL remained unchanged indicating previously unknown downstream pathways of TNFRSF11B in cartilage. CONCLUSION: Results of our 3D in vitro chondrogenesis model indicate that upregulation of TNFRSF11B in lesioned OA cartilage may act as a direct driving factor for chondrocyte to osteoblast transition observed in OA pathophysiology. This transition does not appear to act via the OPG/RANK/RANKL triad common in bone remodeling.

Using deep learning to assist readers during the arbitration process: a lesion-based retrospective evaluation of breast cancer screening performance.

OBJECTIVES: To evaluate if artificial intelligence (AI) can discriminate recalled benign from recalled malignant mammographic screening abnormalities to improve screening performance. METHODS: A total of 2257 full-field digital mammography screening examinations, obtained 2011-2013, of women aged 50-69 years which were recalled for further assessment of 295 malignant out of 305 truly malignant lesions and 2289 benign lesions after independent double-reading with arbitration, were included in this retrospective study. A deep learning AI system was used to obtain a score (0-95) for each recalled lesion, representing the likelihood of breast cancer. The sensitivity on the lesion level and the proportion of women without false-positive ratings (non-FPR) resulting under AI were estimated as a function of the classification cutoff and compared to that of human readers. RESULTS: Using a cutoff of 1, AI decreased the proportion of women with false-positives from 89.9 to 62.0%, non-FPR 11.1% vs. 38.0% (difference 26.9%, 95% confidence interval 25.1-28.8%; p < .001), preventing 30.1% of reader-induced false-positive recalls, while reducing sensitivity from 96.7 to 91.1% (5.6%, 3.1-8.0%) as compared to human reading. The positive predictive value of recall (PPV-1) increased from 12.8 to 16.5% (3.7%, 3.5-4.0%). In women with mass-related lesions (n = 900), the non-FPR was 14.2% for humans vs. 36.7% for AI (22.4%, 19.8-25.3%) at a sensitivity of 98.5% vs. 97.1% (1.5%, 0-3.5%). CONCLUSION: The application of AI during consensus conference might especially help readers to reduce false-positive recalls of masses at the expense of a small sensitivity reduction. Prospective studies are needed to further evaluate the screening benefit of AI in practice. KEY POINTS: • Integrating the use of artificial intelligence in the arbitration process reduces benign recalls and increases the positive predictive value of recall at the expense of some sensitivity loss. • Application of the artificial intelligence system to aid the decision to recall a woman seems particularly beneficial for masses, where the system reaches comparable sensitivity to that of the readers, but with considerably reduced false-positives. • About one-fourth of all recalled malignant lesions are not automatically marked by the system such that their evaluation (AI score) must be retrieved manually by the reader. A thorough reading of screening mammograms by readers to identify suspicious lesions therefore remains mandatory.

Stand-Alone Use of Artificial Intelligence for Digital Mammography and Digital Breast Tomosynthesis Screening: A Retrospective Evaluation.

Background Use of artificial intelligence (AI) as a stand-alone reader for digital mammography (DM) or digital breast tomosynthesis (DBT) breast screening could ease radiologists' workload while maintaining quality. Purpose To retrospectively evaluate the stand-alone performance of an AI system as an independent reader of DM and DBT screening examinations. Materials and Methods Consecutive screening-paired and independently read DM and DBT images acquired between January 2015 and December 2016 were retrospectively collected from the Tomosynthesis Cordoba Screening Trial. An AI system computed a cancer risk score (range, 1-100) for DM and DBT examinations independently. AI stand-alone performance was measured using the area under the receiver operating characteristic curve (AUC) and sensitivity and recall rate at different operating points selected to have noninferior sensitivity compared with the human readings (noninferiority margin, 5%). The recall rate of AI and the human readings were compared using a McNemar test. Results A total of 15 999 DM and DBT examinations (113 breast cancers, including 98 screen-detected and 15 interval cancers) from 15 998 women (mean age, 58 years ± 6 [standard deviation]) were evaluated. AI achieved an AUC of 0.93 (95% CI: 0.89, 0.96) for DM and 0.94 (95% CI: 0.91, 0.97) for DBT. For DM, AI achieved noninferior sensitivity as a single (58.4%; 66 of 113; 95% CI: 49.2, 67.1) or double (67.3%; 76 of 113; 95% CI: 58.2, 75.2) reader, with a reduction in recall rate (P < .001) of up to 2% (95% CI: -2.4, -1.6). For DBT, AI achieved noninferior sensitivity as a single (77%; 87 of 113; 95% CI: 68.4, 83.8) or double (81.4%; 92 of 113; 95% CI: 73.3, 87.5) reader, but with a higher recall rate (P < .001) of up to 12.3% (95% CI: 11.7, 12.9). Conclusion Artificial intelligence could replace radiologists' readings in breast screening, achieving a noninferior sensitivity, with a lower recall rate for digital mammography but a higher recall rate for digital breast tomosynthesis. Published under a CC BY 4.0 license. See also the editorial by Fuchsjäger and Adelsmayr in this issue.

High-impact FN1 mutation decreases chondrogenic potential and affects cartilage deposition via decreased binding to collagen type II.

Osteoarthritis is the most prevalent joint disease worldwide, yet progress in development of effective disease-modifying treatments is slow because of lack of insight into the underlying disease pathways. Therefore, we aimed to identify the causal pathogenic mutation in an early-onset osteoarthritis family, followed by functional studies in human induced pluripotent stem cells (hiPSCs) in an in vitro organoid cartilage model. We demonstrated that the identified causal missense mutation in the gelatin-binding domain of the extracellular matrix protein fibronectin resulted in significant decreased binding capacity to collagen type II. Further analyses of formed hiPSC-derived neo-cartilage tissue highlighted that mutated fibronectin affected chondrogenic capacity and propensity to a procatabolic osteoarthritic state. Together, we demonstrate that binding of fibronectin to collagen type II is crucial for fibronectin downstream gene expression of chondrocytes. We advocate that effective treatment development should focus on restoring or maintaining proper binding between fibronectin and collagen type II.

Impact of Artificial Intelligence Decision Support Using Deep Learning on Breast Cancer Screening Interpretation with Single-View Wide-Angle Digital Breast Tomosynthesis.

Background The high volume of data in digital breast tomosynthesis (DBT) and the lack of agreement on how to best implement it in screening programs makes its use challenging. Purpose To compare radiologist performance when reading single-view wide-angle DBT images with and without an artificial intelligence (AI) system for decision and navigation support. Materials and Methods A retrospective observer study was performed with bilateral mediolateral oblique examinations and corresponding synthetic two-dimensional images acquired between June 2016 and February 2018 with a wide-angle DBT system. Fourteen breast screening radiologists interpreted 190 DBT examinations (90 normal, 26 with benign findings, and 74 with malignant findings), with the reference standard being verified by using histopathologic analysis or at least 1 year of follow-up. Reading was performed in two sessions, separated by at least 4 weeks, with a random mix of examinations being read with and without AI decision and navigation support. Forced Breast Imaging Reporting and Data System (categories 1-5) and level of suspicion (1-100) scores were given per breast by each reader. The area under the receiver operating characteristic curve (AUC) and the sensitivity and specificity were compared between conditions by using the public-domain iMRMC software. The average reading times were compared by using the Wilcoxon signed rank test. Results The 190 women had a median age of 54 years (range, 48-63 years). The examination-based reader-averaged AUC was higher when interpreting results with AI support than when reading unaided (0.88 [95% CI: 0.84, 0.92] vs 0.85 [95% CI: 0.80, 0.89], respectively; P = .01). The average sensitivity increased with AI support (64 of 74, 86% [95% CI: 80%, 92%] vs 60 of 74, 81% [95% CI: 74%, 88%]; P = .006), whereas no differences in the specificity (85 of 116, 73.3% [95% CI: 65%, 81%] vs 83 of 116, 71.6% [95% CI: 65%, 78%]; P = .48) or reading time (48 seconds vs 45 seconds; P = .35) were detected. Conclusion Using a single-view digital breast tomosynthesis (DBT) and artificial intelligence setup could allow for a more effective screening program with higher performance, especially in terms of an increase in cancers detected, than using single-view DBT alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Chan and Helvie in this issue.

Cartilage from human-induced pluripotent stem cells: comparison with neo-cartilage from chondrocytes and bone marrow mesenchymal stromal cells.

Cartilage has little intrinsic capacity for repair, so transplantation of exogenous cartilage cells is considered a realistic option for cartilage regeneration. We explored whether human-induced pluripotent stem cells (hiPSCs) could represent such unlimited cell sources for neo-cartilage comparable to human primary articular chondrocytes (hPACs) or human bone marrow-derived mesenchymal stromal cells (hBMSCs). For this, chondroprogenitor cells (hiCPCs) and hiPSC-derived mesenchymal stromal cells (hiMSCs) were generated from two independent hiPSC lines and characterized by morphology, flow cytometry, and differentiation potential. Chondrogenesis was compared to hBMSCs and hPACs by histology, immunohistochemistry, and RT-qPCR, while similarities were estimated based on Pearson correlations using a panel of 20 relevant genes. Our data show successful differentiations of hiPSC into hiMSCs and hiCPCs. Characteristic hBMSC markers were shared between hBMSCs and hiMSCs, with the exception of CD146 and CD45. However, neo-cartilage generated from hiMSCs showed low resemblances when compared to hBMSCs (53%) and hPACs (39%) characterized by lower collagen type 2 and higher collagen type 1 expression. Contrarily, hiCPC neo-cartilage generated neo-cartilage more similar to hPACs (65%), with stronger expression of matrix deposition markers. Our study shows that taking a stepwise approach to generate neo-cartilage from hiPSCs via chondroprogenitor cells results in strong similarities to neo-cartilage of hPACs within 3 weeks following chondrogenesis, making them a potential candidate for regenerative therapies. Contrarily, neo-cartilage deposited by hiMSCs seems more prone to hypertrophic characteristics compared to hPACs. We therefore compared chondrocytes derived from hiMSCs and hiCPCs with hPACs and hBMSCs to outline similarities and differences between their neo-cartilage and establish their potential suitability for regenerative medicine and disease modelling.

Impact of artificial intelligence support on accuracy and reading time in breast tomosynthesis image interpretation: a multi-reader multi-case study.

OBJECTIVES: Digital breast tomosynthesis (DBT) increases sensitivity of mammography and is increasingly implemented in breast cancer screening. However, the large volume of images increases the risk of reading errors and reading time. This study aims to investigate whether the accuracy of breast radiologists reading wide-angle DBT increases with the aid of an artificial intelligence (AI) support system. Also, the impact on reading time was assessed and the stand-alone performance of the AI system in the detection of malignancies was compared to the average radiologist. METHODS: A multi-reader multi-case study was performed with 240 bilateral DBT exams (71 breasts with cancer lesions, 70 breasts with benign findings, 339 normal breasts). Exams were interpreted by 18 radiologists, with and without AI support, providing cancer suspicion scores per breast. Using AI support, radiologists were shown examination-based and region-based cancer likelihood scores. Area under the receiver operating characteristic curve (AUC) and reading time per exam were compared between reading conditions using mixed-models analysis of variance. RESULTS: On average, the AUC was higher using AI support (0.863 vs 0.833; p = 0.0025). Using AI support, reading time per DBT exam was reduced (p < 0.001) from 41 (95% CI = 39-42 s) to 36 s (95% CI = 35- 37 s). The AUC of the stand-alone AI system was non-inferior to the AUC of the average radiologist (+0.007, p = 0.8115). CONCLUSIONS: Radiologists improved their cancer detection and reduced reading time when evaluating DBT examinations using an AI reading support system. KEY POINTS: • Radiologists improved their cancer detection accuracy in digital breast tomosynthesis (DBT) when using an AI system for support, while simultaneously reducing reading time. • The stand-alone breast cancer detection performance of an AI system is non-inferior to the average performance of radiologists for reading digital breast tomosynthesis exams. • The use of an AI support system could make advanced and more reliable imaging techniques more accessible and could allow for more cost-effective breast screening programs with DBT.

AI-based Strategies to Reduce Workload in Breast Cancer Screening with Mammography and Tomosynthesis: A Retrospective Evaluation.

Background The workflow of breast cancer screening programs could be improved given the high workload and the high number of false-positive and false-negative assessments. Purpose To evaluate if using an artificial intelligence (AI) system could reduce workload without reducing cancer detection in breast cancer screening with digital mammography (DM) or digital breast tomosynthesis (DBT). Materials and Methods Consecutive screening-paired and independently read DM and DBT images acquired from January 2015 to December 2016 were retrospectively collected from the Córdoba Tomosynthesis Screening Trial. The original reading settings were single or double reading of DM or DBT images. An AI system computed a cancer risk score for DM and DBT examinations independently. Each original setting was compared with a simulated autonomous AI triaging strategy (the least suspicious examinations for AI are not human-read; the rest are read in the same setting as the original, and examinations not recalled by radiologists but graded as very suspicious by AI are recalled) in terms of workload, sensitivity, and recall rate. The McNemar test with Bonferroni correction was used for statistical analysis. Results A total of 15 987 DM and DBT examinations (which included 98 screening-detected and 15 interval cancers) from 15 986 women (mean age ± standard deviation, 58 years ± 6) were evaluated. In comparison with double reading of DBT images (568 hours needed, 92 of 113 cancers detected, 706 recalls in 15 987 examinations), AI with DBT would result in 72.5% less workload (P < .001, 156 hours needed), noninferior sensitivity (95 of 113 cancers detected, P = .38), and 16.7% lower recall rate (P < .001, 588 recalls in 15 987 examinations). Similar results were obtained for AI with DM. In comparison with the original double reading of DM images (222 hours needed, 76 of 113 cancers detected, 807 recalls in 15 987 examinations), AI with DBT would result in 29.7% less workload (P < .001), 25.0% higher sensitivity (P < .001), and 27.1% lower recall rate (P < .001). Conclusion Digital mammography and digital breast tomosynthesis screening strategies based on artificial intelligence systems could reduce workload up to 70%. Published under a CC BY 4.0 license.

A Novel Deep Learning Based Computer-Aided Diagnosis System Improves the Accuracy and Efficiency of Radiologists in Reading Biparametric Magnetic Resonance Images of the Prostate: Results of a Multireader, Multicase Study.

OBJECTIVE: The aim of this study was to evaluate the effect of a deep learning based computer-aided diagnosis (DL-CAD) system on radiologists' interpretation accuracy and efficiency in reading biparametric prostate magnetic resonance imaging scans. MATERIALS AND METHODS: We selected 100 consecutive prostate magnetic resonance imaging cases from a publicly available data set (PROSTATEx Challenge) with and without histopathologically confirmed prostate cancer. Seven board-certified radiologists were tasked to read each case twice in 2 reading blocks (with and without the assistance of a DL-CAD), with a separation between the 2 reading sessions of at least 2 weeks. Reading tasks were to localize and classify lesions according to Prostate Imaging Reporting and Data System (PI-RADS) v2.0 and to assign a radiologist's level of suspicion score (scale from 1-5 in 0.5 increments; 1, benign; 5, malignant). Ground truth was established by consensus readings of 3 experienced radiologists. The detection performance (receiver operating characteristic curves), variability (Fleiss κ), and average reading time without DL-CAD assistance were evaluated. RESULTS: The average accuracy of radiologists in terms of area under the curve in detecting clinically significant cases (PI-RADS ≥4) was 0.84 (95% confidence interval [CI], 0.79-0.89), whereas the same using DL-CAD was 0.88 (95% CI, 0.83-0.94) with an improvement of 4.4% (95% CI, 1.1%-7.7%; P = 0.010). Interreader concordance (in terms of Fleiss κ) increased from 0.22 to 0.36 (P = 0.003). Accuracy of radiologists in detecting cases with PI-RADS ≥3 was improved by 2.9% (P = 0.10). The median reading time in the unaided/aided scenario was reduced by 21% from 103 to 81 seconds (P < 0.001). CONCLUSIONS: Using a DL-CAD system increased the diagnostic accuracy in detecting highly suspicious prostate lesions and reduced both the interreader variability and the reading time.

Can artificial intelligence reduce the interval cancer rate in mammography screening?

OBJECTIVES: To investigate whether artificial intelligence (AI) can reduce interval cancer in mammography screening. MATERIALS AND METHODS: Preceding screening mammograms of 429 consecutive women diagnosed with interval cancer in Southern Sweden between 2013 and 2017 were analysed with a deep learning-based AI system. The system assigns a risk score from 1 to 10. Two experienced breast radiologists reviewed and classified the cases in consensus as true negative, minimal signs or false negative and assessed whether the AI system correctly localised the cancer. The potential reduction of interval cancer was calculated at different risk score thresholds corresponding to approximately 10%, 4% and 1% recall rates. RESULTS: A statistically significant correlation between interval cancer classification groups and AI risk score was observed (p < .0001). AI scored one in three (143/429) interval cancer with risk score 10, of which 67% (96/143) were either classified as minimal signs or false negative. Of these, 58% (83/143) were correctly located by AI, and could therefore potentially be detected at screening with the aid of AI, resulting in a 19.3% (95% CI 15.9-23.4) reduction of interval cancer. At 4% and 1% recall thresholds, the reduction of interval cancer was 11.2% (95% CI 8.5-14.5) and 4.7% (95% CI 3.0-7.1). The corresponding reduction of interval cancer with grave outcome (women who died or with stage IV disease) at risk score 10 was 23% (8/35; 95% CI 12-39). CONCLUSION: The use of AI in screen reading has the potential to reduce the rate of interval cancer without supplementary screening modalities. KEY POINTS: • Retrospective study showed that AI detected 19% of interval cancer at the preceding screening exam that in addition showed at least minimal signs of malignancy. Importantly, these were correctly localised by AI, thus obviating supplementary screening modalities. • AI could potentially reduce a proportion of particularly aggressive interval cancers. • There was a correlation between AI risk score and interval cancer classified as true negative, minimal signs or false negative.

Iodine quantification in limited angle tomography.

PURPOSE: To develop and test the feasibility of a two-pass iterative reconstruction algorithm with material decomposition designed to obtain quantitative iodine measurements in digital breast tomosynthesis. METHODS: Contrast-enhanced mammography has shown promise as a cost-effective alternative to magnetic resonance imaging for imaging breast cancer, especially in dense breasts. However, one limitation is the poor quantification of iodine contrast since the true three-dimensional lesion shape cannot be inferred from the two-dimensional (2D) projection. Use of limited angle tomography can potentially overcome this limitation by segmenting the iodine map generated by the first-pass reconstruction using a convolutional neural network, and using this segmentation to restrict the iodine distribution in the second pass of the reconstruction. To evaluate the performance of the algorithms, a set of 2D digital breast phantoms containing targets with varying iodine concentration was used. In each breast phantom, a single simulated lesion with a random size (4 to 8 mm) was placed in a random location within each phantom, with the iodine distribution defined as either homogeneous or rim-enhanced and blood iodine concentration set between 1.4 and 5.6 mg/mL. Limited angle projection data of these phantoms were simulated for wide and narrow angle geometries, and the proposed reconstruction and segmentation algorithms were applied. RESULTS: The median Dice similarity coefficient of the segmented masks was 0.975 for the wide angle data and 0.926 for the narrow angle data. Using these segmentations during the second reconstruction pass resulted in an improvement in the concentration estimates (mean estimated-to-true concentration ratio, before and after second pass: 48% to 73% for wide angle; 30% to 73% for narrow angle), and a reduction in the coefficient of variation of the estimates (55% to 27% for wide angle; 54% to 35% for narrow angle). CONCLUSION: We demonstrate that the proposed two-pass reconstruction can potentially improve accuracy and precision of iodine quantification in contrast-enhanced tomosynthesis.

Artificial intelligence for breast cancer detection in mammography: experience of use of the ScreenPoint Medical Transpara system in 310 Japanese women.

BACKGROUND: To compare the breast cancer detection performance in digital mammograms of a panel of three unaided human readers (HR) versus a stand-alone artificial intelligence (AI)-based Transpara system in a population of Japanese women. METHODS: The subjects were 310 Japanese female outpatients who underwent digital mammographic examinations between January 2018 and October 2018. A panel of three HR provided a Breast Imaging Reporting and Data System (BI-RADS) score, and Transpara system provided an interactive decision support score and an examination-based cancer likelihood score. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared under each of reading conditions. RESULTS: The AUC was higher for human readers than with stand-alone Transpara system (human readers 0.816; Transpara system 0.706; difference 0.11; P < 0.001). The sensitivity of the unaided HR for diagnosis was 89% and specificity was 86%. The sensitivity of stand-alone Transpara system for cutoff scores of 4 and 7 were 93% and 85%, and specificities were 45% and 67%, respectively. CONCLUSIONS: Although the diagnostic performance of Transpara system was statistically lower than that of HR, the recent advances in AI algorithms are expected to reduce the difference between computers and human experts in detecting breast cancer.