ObjectiveTo uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage.MethodsWe performed RNA sequencing in 130 samples (n=35 and n=30 pairs for ...messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed differential expression (DE) analysis of miRNA and mRNAs. To build an OA-specific miRNA interactome, a prioritisation scheme was applied based on inverse Pearson’s correlations and inverse DE of miRNAs and mRNAs. Subsequently, these were filtered by those present in predicted (TargetScan/microT-CDS) and/or experimentally validated (miRTarBase/TarBase) public databases. Pathway enrichment analysis was applied to elucidate OA-related pathways likely mediated by miRNA regulatory mechanisms.ResultsWe found 142 miRNAs and 2387 mRNAs to be differentially expressed between lesioned and preserved OA articular cartilage. After applying prioritisation towards likely miRNA-mRNA targets, a regulatory network of 62 miRNAs targeting 238 mRNAs was created. Subsequent pathway enrichment analysis of these mRNAs (or genes) elucidated that genes within the ‘nervous system development’ are likely mediated by miRNA regulatory mechanisms (familywise error=8.4×10−5). Herein NTF3 encodes neurotrophin-3, which controls survival and differentiation of neurons and which is closely related to the nerve growth factor.ConclusionsBy an integrated approach of miRNA and mRNA sequencing data of OA cartilage, an OA miRNA interactome and related pathways were elucidated. Our functional data demonstrated interacting levels at which miRNA affects expression of genes in the cartilage and exemplified the complexity of functionally validating a network of genes that may be targeted by multiple miRNAs.
Purpose To compare breast cancer detection performance of radiologists reading mammographic examinations unaided versus supported by an artificial intelligence (AI) system. Materials and Methods An ...enriched retrospective, fully crossed, multireader, multicase, HIPAA-compliant study was performed. Screening digital mammographic examinations from 240 women (median age, 62 years; range, 39-89 years) performed between 2013 and 2017 were included. The 240 examinations (100 showing cancers, 40 leading to false-positive recalls, 100 normal) were interpreted by 14 Mammography Quality Standards Act-qualified radiologists, once with and once without AI support. The readers provided a Breast Imaging Reporting and Data System score and probability of malignancy. AI support provided radiologists with interactive decision support (clicking on a breast region yields a local cancer likelihood score), traditional lesion markers for computer-detected abnormalities, and an examination-based cancer likelihood score. The area under the receiver operating characteristic curve (AUC), specificity and sensitivity, and reading time were compared between conditions by using mixed-models analysis dof variance and generalized linear models for multiple repeated measurements. Results On average, the AUC was higher with AI support than with unaided reading (0.89 vs 0.87, respectively; P = .002). Sensitivity increased with AI support (86% 86 of 100 vs 83% 83 of 100; P = .046), whereas specificity trended toward improvement (79% 111 of 140) vs 77% 108 of 140; P = .06). Reading time per case was similar (unaided, 146 seconds; supported by AI, 149 seconds; P = .15). The AUC with the AI system alone was similar to the average AUC of the radiologists (0.89 vs 0.87). Conclusion Radiologists improved their cancer detection at mammography when using an artificial intelligence system for support, without requiring additional reading time. Published under a CC BY 4.0 license. See also the editorial by Bahl in this issue.
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.
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 (DgN) 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 DgN estimated for the proposed phantoms was concordant with that absorbed by the patient‐specific phantoms to within 5% (CC) and 4% (MLO). These DgN estimates were over 30% lower than those estimated with the homogeneous models, which overestimated the average DgN 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.
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.
Iodine quantification in limited angle tomography Michielsen, Koen; Rodríguez‐Ruiz, Alejandro; Reiser, Ingrid ...
Medical physics (Lancaster),
October 2020, Letnik:
47, Številka:
10
Journal Article
Recenzirano
Odprti dostop
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.
To characterize and develop a patient-based 3D model of the compressed breast undergoing mammography and breast tomosynthesis. During this IRB-approved, HIPAA-compliant study, 50 women were recruited ...to undergo 3D breast surface imaging with structured light (SL) during breast compression, along with simultaneous acquisition of a tomosynthesis image. A pair of SL systems were used to acquire 3D surface images by projecting 24 different patterns onto the compressed breast and capturing their reflection off the breast surface in approximately 12-16 s. The 3D surface was characterized and modeled via principal component analysis. The resulting surface model was combined with a previously developed 2D model of projected compressed breast shapes to generate a full 3D model. Data from ten patients were discarded due to technical problems during image acquisition. The maximum breast thickness (found at the chest-wall) had an average value of 56 mm, and decreased 13% towards the nipple (breast tilt angle of 5.2°). The portion of the breast not in contact with the compression paddle or the support table extended on average 17 mm, 18% of the chest-wall to nipple distance. The outermost point along the breast surface lies below the midline of the total thickness. A complete 3D model of compressed breast shapes was created and implemented as a software application available for download, capable of generating new random realistic 3D shapes of breasts undergoing compression. Accurate characterization and modeling of the breast curvature and shape was achieved and will be used for various image processing and clinical tasks.
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.
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.
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.
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).
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.
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