Search

Purpose Colitis refers to inflammation of the inner lining of the colon that is frequently associated with infection and allergic reactions. In this paper, we propose deep convolutional neural networks methods for lesion-level colitis detection and a support vector machine ( SVM) classifier for patient-level colitis diagnosis on routine abdominal CT scans. Methods The recently developed Faster Region-based Convolutional Neural Network (Faster RCNN) is utilized for lesion-level colitis detection. For each 2D slice, rectangular region proposals are generated by region proposal networks ( RPN). Then, each region proposal is jointly classified and refined by a softmax classifier and bounding-box regressor. Two convolutional neural networks, eight layers of ZF net and 16 layers of VGG net are compared for colitis detection. Finally, for each patient, the detections on all 2D slices are collected and a SVM classifier is applied to develop a patient-level diagnosis. We trained and evaluated our method with 80 colitis patients and 80 normal cases using 4 × 4-fold cross validation. Results For lesion-level colitis detection, with ZF net, the mean of average precisions ( mAP) were 48.7% and 50.9% for RCNN and Faster RCNN, respectively. The detection system achieved sensitivities of 51.4% and 54.0% at two false positives per patient for RCNN and Faster RCNN, respectively. With VGG net, Faster RCNN increased the m AP to 56.9% and increased the sensitivity to 58.4% at two false positive per patient. For patient-level colitis diagnosis, with ZF net, the average areas under the ROC curve ( AUC) were 0.978 ± 0.009 and 0.984 ± 0.008 for RCNN and Faster RCNN method, respectively. The difference was not statistically significant with P = 0.18. At the optimal operating point, the RCNN method correctly identified 90.4% (72.3/80) of the colitis patients and 94.0% (75.2/80) of normal cases. The sensitivity improved to 91.6% (73.3/80) and the specificity improved to 95.0% (76.0/80) for the Faster RCNN method. With VGG net, Faster RCNN increased the AUC to 0.986 ± 0.007 and increased the diagnosis sensitivity to 93.7% (75.0/80) and specificity was unchanged at 95.0% (76.0/80). Conclusion Colitis detection and diagnosis by deep convolutional neural networks is accurate and promising for future clinical application. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of lesion volumetry in hepatic CT as a function of various imaging acquisition parameters. Methods: An anthropomorphic abdominal phantom with removable liver inserts was designed for this study. Two liver inserts, each containing 19 synthetic lesions with varying diameter (6-40 mm), shape, contrast (10-65 HU), and both homogenous and mixed-density were designed to have background and lesion CT values corresponding to arterial and portal-venous phase imaging, respectively. The two phantoms were scanned using two commercial CT scanners (GE 750 HD and Siemens Biograph mCT) across a set of imaging protocols (four slice thicknesses, three effective mAs, two convolution kernels, two pitches). Two repeated scans were collected for each imaging protocol. All scans were analyzed using a matched-filter estimator for volume estimation, resulting in 6080 volume measurements across all of the synthetic lesions in the two liver phantoms. A subset of portal venous phase scans was also analyzed using a semi-automatic segmentation algorithm, resulting in about 900 additional volume measurements. Lesions associated with large measurement error (quantified by root mean square error) for most imaging protocols were considered not measurable by the volume estimation tools and excluded for the statistical analyses. Imaging protocols were grouped into distinct imaging conditions based on ANOVA analysis of factors for repeatability testing. Statistical analyses, including overall linearity analysis, grouped bias analysis with standard deviation evaluation, and repeatability analysis, were performed to assess the accuracy and precision of the liver lesion volume biomarker. Results: Lesions with lower contrast and size ≤10 mm were associated with higher measurement error and were excluded from further analysis. Lesion size, contrast, imaging slice thickness, dose, and scanner were found to be factors substantially influencing volume estimation. Twenty-four distinct repeatable imaging conditions were determined as protocols for each scanner with a fixed slice thickness and dose. For the matched-filter estimation approach, strong linearity was observed for all imaging data for lesions ≥20 mm. For the Siemens scanner with 50 mAs effective dose at 0.6 mm slice thickness, grouped bias was about -10%. For all other repeatable imaging conditions with both scanners, grouped biases were low (-3%-3%). There was a trend of increasing standard deviation with decreasing dose. For each fixed dose, the standard deviations were similar among the three larger slice thicknesses (1.25, 2.5, 5 mm for GE, 1.5, 3, 5 mm for Siemens). Repeatability coefficients ranged from about 8% to 75% and showed similar trend to grouped standard deviation. For the segmentation approach, the results led to similar conclusions for both lesion characteristic factors and imaging factors but with increasing magnitude in all the error metrics assessed. Conclusions: Results showed that liver lesion volumetry was strongly dependent on lesion size, contrast, acquisition dose, and their interactions. The overall performances were similar for images reconstructed with larger slice thicknesses, clinically used pitches, kernels, and doses. Conditions that yielded repeatable measurements were identified and they agreed with the Quantitative Imaging Biomarker Alliance's (QIBA) profile requirements in general. The authors' findings also suggest potential refinements to these guidelines for the tumor volume biomarker, especially for soft-tissue lesions. [ABSTRACT FROM AUTHOR]

The availability of large medical image datasets is critical in many applications, such as training and testing of computer-aided diagnosis systems, evaluation of segmentation algorithms, and conducting perceptual studies. However, collection of data and establishment of ground truth for medical images are both costly and difficult. To address this problem, we are developing an image blending tool that allows users to modify or supplement existing datasets by seamlessly inserting a lesion extracted from a source image into a target image. In this study, we focus on the application of this tool to pulmonary nodules in chest CT exams. We minimize the impact of user skill on the perceived quality of the composite image by limiting user involvement to two simple steps: the user first draws a casual boundary around a nodule in the source, and, then, selects the center of desired insertion area in the target. We demonstrate the performance of our system on clinical samples, and report the results of a reader study evaluating the realism of inserted nodules compared to clinical nodules. We further evaluate our image blending techniques using phantoms simulated under different noise levels and reconstruction filters. Specifically, we compute the area under the ROC curve of the Hotelling observer (HO) and noise power spectrum of regions of interest enclosing native and inserted nodules, and compare the detectability, noise texture, and noise magnitude of inserted and native nodules. Our results indicate the viability of our approach for insertion of pulmonary nodules in clinical CT images. [ABSTRACT FROM PUBLISHER]

Purpose: To determine inter-related factors that contribute substantially to measurement error of pulmonary nodule measurements with CT by assessing a large-scale dataset of phantom scans and to quantitatively validate the repeatability and reproducibility of a subset containing nodules and CT acquisitions consistent with the Quantitative Imaging Biomarker Alliance (QIBA) metrology recommendations. Methods: The dataset has about 40 000 volume measurements of 48 nodules (5-20 mm, four shapes, three radiodensities) estimated by a matched-filter estimator from CT images involving 72 imaging protocols. Technical assessment was performed under a framework suggested by QIBA, which aimed to minimize the inconsistency of terminologies and techniques used in the literature. Accuracy and precision of lung nodule volume measurements were examined by analyzing the linearity, bias, variance, root mean square error (RMSE), repeatability, reproducibility, and significant and substantial factors that contribute to the measurement error. Statistical methodologies including linear regression, analysis of variance, and restricted maximum likelihood were applied to estimate the aforementioned metrics. The analysis was performed on both the whole dataset and a subset meeting the criteria proposed in the QIBA Profile document. Results: Strong linearity was observed for all data. Size, slice thickness×collimation, and randomness in attachment to vessels or chest wall were the main sources of measurement error. Grouping the data by nodule size and slice thickness×collimation, the standard deviation (3.9%-28%), and RMSE (4.4%-68%) tended to increase with smaller nodule size and larger slice thickness. For 5, 8, 10, and 20 mm nodules with reconstruction slice thickness ≤0.8, 3, 3, and 5 mm, respectively, the measurements were almost unbiased (-3.0% to 3.0%). Repeatability coefficients (RCs) were from 6.2% to 40%. Pitch of 0.9, detail kernel, and smaller slice thicknesses yielded better (smaller) RCs than those from pitch of 1.2, medium kernel, and larger slice thicknesses. Exposure showed no impact on RC. The overall reproducibility coefficient (RDC) was 45%, and reduced to about 20%-30% when the slice thickness and collimation were fixed. For nodules and CT imaging complying with the QIBA Profile (QIBA Profile subset), the measurements were highly repeatable and reproducible in spite of variations in nodule characteristics and imaging protocols. The overall measurement error was small and mostly due to the randomness in attachment. The bias, standard deviation, and RMSE grouped by nodule size and slice thickness×collimation in the QIBA Profile subset were within ±3%, 4%, and 5%, respectively. RCs are within 11% and the overall RDC is equal to 11%. Conclusions: The authors have performed a comprehensive technical assessment of lung nodule volumetry with a matched-filter estimator from CT scans of synthetic nodules and identified the main sources of measurement error among various nodule characteristics and imaging parameters. The results confirm that the QIBA Profile set is highly repeatable and reproducible. These phantom study results can serve as a bound on the clinical performance achievable with volumetric CT measurements of pulmonary nodules. [ABSTRACT FROM AUTHOR]

The goal of this work is to design computerized image analysis techniques for automatically characterizing lung nodule subtlety in CT images. Automated subtlety estimation methods may help in computer-aided detection (CAD) assessment by quantifying dataset difficulty and facilitating comparisons among different CAD algorithms. A dataset containing 813 nodules from 499 patients was obtained from the Lung Image Database Consortium. Each nodule was evaluated by four radiologists regarding nodule subtlety using a 5-point rating scale (1: most subtle). We developed a 3D technique for segmenting lung nodules using a prespecified initial ROI. Texture and morphological features were automatically extracted from the segmented nodules and their margins. The dataset was partitioned into trainers and testers using a 1:1 ratio. An artificial neural network (ANN) was trained with average reader subtlety scores as the reference. Effective features for characterizing nodule subtlety were selected based on the training set using the ANN and a stepwise feature selection method. The performance of the classifier was evaluated using prediction probability (PK) as an agreement measure, which is considered a generalization of the area under the receiver operating characteristic curve when the reference standard is multi-level. Using an ANN classifier trained with a set of 2 features (selected from a total of 30 features), including compactness and average gray value, the test concordance between computer scores and the average reader scores was 0.789 ± 0.014. Our results show that the proposed method had strong agreement with the average of subtlety scores provided by radiologists. [ABSTRACT FROM AUTHOR]

Abstract: Computer-aided detection (CAD) systems have been shown to improve the diagnostic performance of CT colonography (CTC) in the detection of premalignant colorectal polyps. Despite the improvement, the overall system is not optimal. CAD annotations on true lesions are incorrectly dismissed, and false positives are misinterpreted as true polyps. Here, we conduct an observer performance study utilizing distributed human intelligence in the form of anonymous knowledge workers (KWs) to investigate human performance in classifying polyp candidates under different presentation strategies. We evaluated 600 polyp candidates from 50 patients, each case having at least one polyp ⩾6mm, from a large database of CTC studies. Each polyp candidate was labeled independently as a true or false polyp by 20KWs and an expert radiologist. We asked each labeler to determine whether the candidate was a true polyp after looking at a single 3D-rendered image of the candidate and after watching a video fly-around of the candidate. We found that distributed human intelligence improved significantly when presented with the additional information in the video fly-around. We noted that performance degraded with increasing interpretation time and increasing difficulty, but distributed human intelligence performed better than our CAD classifier for “easy” and “moderate” polyp candidates. Further, we observed numerous parallels between the expert radiologist and the KWs. Both showed similar improvement in classification moving from single-image to video interpretation. Additionally, difficulty estimates obtained from the KWs using an expectation maximization algorithm correlated well with the difficulty rating assigned by the expert radiologist. Our results suggest that distributed human intelligence is a powerful tool that will aid in the development of CAD for CTC. [Copyright &y& Elsevier]

Abstract: We investigated a Pareto front approach to improve polyp detection algorithms for CT colonography (CTC). A dataset of 56 CTC colon surfaces with 87 proven positive detections of 53 polyps sized 4–60mm was used to evaluate the performance of a one-step and a two-step curvature-based region growing algorithm. The algorithmic performance was statistically evaluated and compared based on the Pareto optimal solutions from 20 experiments by evolutionary algorithms. The false positive rate was lower (p <0.05) by the two-step algorithm than by the one-step for 63% of all possible operating points. While operating at a suitable sensitivity level such as 90.8% (79/87) or 88.5% (77/87), the false positive rate was reduced by 24.4% (95% confidence intervals 17.9–31.0%) or 45.8% (95% confidence intervals 40.1–51.0%), respectively. We demonstrated that, with a proper experimental design, the Pareto optimization process can effectively help in fine-tuning and redesigning polyp detection algorithms. [Copyright &y& Elsevier]

The future of artificial intelligence (AI) safety is expected to include bias mitigation methods from development to application. The complexity and integration of these methods could grow in conjunction with advances in AI and human-AI interactions. Numerous methods are being proposed to mitigate bias, but without a structured way to compare their strengths and weaknesses. In this work, we present two approaches to systematically amplify subgroup performance bias. These approaches allow for the evaluation and comparison of the effectiveness of bias mitigation methods on AI models by varying the degrees of bias, and can be applied to any classification model. We used these approaches to compare four off-the-shelf bias mitigation methods. Both amplification approaches promote the development of learning shortcuts in which the model forms associations between patient attributes and AI output. We demonstrate these approaches in a case study, evaluating bias in the determination of COVID status from chest x-rays. The maximum achieved increase in performance bias, measured as a difference in predicted prevalence, was 72% and 32% for bias between subgroups related to patient sex and race, respectively. These changes in predicted prevalence were not accompanied by substantial changes in the differences in subgroup area under the receiver operating characteristic curves, indicating that the increased bias is due to the formation of learning shortcuts, not a difference in ability to distinguish positive and negative patients between subgroups.

Purpose: Synthetic datasets hold the potential to offer cost-effective alternatives to clinical data, ensuring privacy protections and potentially addressing biases in clinical data. We present a method leveraging such datasets to train a machine learning algorithm applied as part of a computer-aided detection (CADe) system., Approach: Our proposed approach utilizes clinically acquired computed tomography (CT) scans of a physical anthropomorphic phantom into which manufactured lesions were inserted to train a machine learning algorithm. We treated the training database obtained from the anthropomorphic phantom as a simplified representation of clinical data and increased the variability in this dataset using a set of randomized and parameterized augmentations. Furthermore, to mitigate the inherent differences between phantom and clinical datasets, we investigated adding unlabeled clinical data into the training pipeline., Results: We apply our proposed method to the false positive reduction stage of a lung nodule CADe system in CT scans, in which regions of interest containing potential lesions are classified as nodule or non-nodule regions. Experimental results demonstrate the effectiveness of the proposed method; the system trained on labeled data from physical phantom scans and unlabeled clinical data achieves a sensitivity of 90% at eight false positives per scan. Furthermore, the experimental results demonstrate the benefit of the physical phantom in which the performance in terms of competitive performance metric increased by 6% when a training set consisting of 50 clinical CT scans was enlarged by the scans obtained from the physical phantom., Conclusions: The scalability of synthetic datasets can lead to improved CADe performance, particularly in scenarios in which the size of the labeled clinical data is limited or subject to inherent bias. Our proposed approach demonstrates an effective utilization of synthetic datasets for training machine learning algorithms., (© 2024 The Authors.)

Background: Positive and negative likelihood ratios (PLR and NLR) are important metrics of accuracy for diagnostic devices with a binary output. However, the properties of Bayesian and frequentist interval estimators of PLR/NLR have not been extensively studied and compared. In this study, we explore the potential use of the Bayesian method for interval estimation of PLR/NLR, and, more broadly, for interval estimation of the ratio of two independent proportions., Methods: We develop a Bayesian-based approach for interval estimation of PLR/NLR for use as a part of a diagnostic device performance evaluation. Our approach is applicable to a broader setting for interval estimation of any ratio of two independent proportions. We compare score and Bayesian interval estimators for the ratio of two proportions in terms of the coverage probability (CP) and expected interval width (EW) via extensive experiments and applications to two case studies. A supplementary experiment was also conducted to assess the performance of the proposed exact Bayesian method under different priors., Results: Our experimental results show that the overall mean CP for Bayesian interval estimation is consistent with that for the score method (0.950 vs. 0.952), and the overall mean EW for Bayesian is shorter than that for score method (15.929 vs. 19.724). Application to two case studies showed that the intervals estimated using the Bayesian and frequentist approaches are very similar., Discussion: Our numerical results indicate that the proposed Bayesian approach has a comparable CP performance with the score method while yielding higher precision (i.e. a shorter EW).

Innovation in medical imaging artificial intelligence (AI)/machine learning (ML) demands extensive data collection, algorithmic advancements, and rigorous performance assessments encompassing aspects such as generalizability, uncertainty, bias, fairness, trustworthiness, and interpretability. Achieving widespread integration of AI/ML algorithms into diverse clinical tasks will demand a steadfast commitment to overcoming issues in model design, development, and performance assessment. The complexities of AI/ML clinical translation present substantial challenges, requiring engagement with relevant stakeholders, assessment of cost-effectiveness for user and patient benefit, timely dissemination of information relevant to robust functioning throughout the AI/ML lifecycle, consideration of regulatory compliance, and feedback loops for real-world performance evidence. This commentary addresses several hurdles for the development and adoption of AI/ML technologies in medical imaging. Comprehensive attention to these underlying and often subtle factors is critical not only for tackling the challenges but also for exploring novel opportunities for the advancement of AI in radiology., Competing Interests: Ravi K. Samala – nothing to disclose. Karen Drukker – receives royalties from Hologic. Amita Shukla-Dave – nothing to disclose. Heang-Ping Chan – nothing to disclose. Berkman Sahiner – nothing to disclose. Nicholas Petrick – nothing to disclose. Hayit Greenspan - nothing to disclose. Usman Mahmood – nothing to disclose. Ronald M Summers – received royalties for patents or software licenses from iCAD, Philips, ScanMed, Translation Holdings, PingAn and MGB, received research support from PingAn through a Cooperative Research and Development Agreement, not related to this work. Georgia Tourassi – nothing to disclose. Thomas M. Deserno – nothing to disclose. Daniele Regge – nothing to disclose. Janne J. Näppi – has received royalties from Hologic and from MEDIAN Technologies, through the University of Chicago licensing, not related to this work. Hiroyuki Yoshida – has received royalties from licensing fees to Hologic and Medians Technologies through the University of Chicago licensing, not related to this work. Zhimin Huo – nothing to disclose. Quan Chen – has received compensations from Carina Medical LLC, not related to this work, pro-vides consulting services for Reflexion Medical, not related to this work. Daniel Vergara – nothing to disclose. Kenny Cha – nothing to disclose. Richard Mazurchuk – nothing to disclose. Kevin T. Grizzard – nothing to disclose. Henkjan Huisman – has received grant support from Siemens Healthineers and Canon Medical for a scientific research project, not related to this work. Lia Morra – has received funding from HealthTriagesrl, not related to this work. Kenji Suzuki – provides consulting services for Canon Medical, not related to this work. Samuel G. Armato III – has received royalties and licensing fees for computer-aided diagnosis through the University of Chicago, not related to this work., (Published by Oxford University Press on behalf of the British Institute of Radiology 2024.)

Background and Aims: The American Society for Gastrointestinal Endoscopy (ASGE) AI Task Force along with experts in endoscopy, technology space, regulatory authorities, and other medical subspecialties initiated a consensus process that analyzed the current literature, highlighted potential areas, and outlined the necessary research in artificial intelligence (AI) to allow a clearer understanding of AI as it pertains to endoscopy currently., Methods: A modified Delphi process was used to develop these consensus statements., Results: Statement 1: Current advances in AI allow for the development of AI-based algorithms that can be applied to endoscopy to augment endoscopist performance in detection and characterization of endoscopic lesions. Statement 2: Computer vision-based algorithms provide opportunities to redefine quality metrics in endoscopy using AI, which can be standardized and can reduce subjectivity in reporting quality metrics. Natural language processing-based algorithms can help with the data abstraction needed for reporting current quality metrics in GI endoscopy effortlessly. Statement 3: AI technologies can support smart endoscopy suites, which may help optimize workflows in the endoscopy suite, including automated documentation. Statement 4: Using AI and machine learning helps in predictive modeling, diagnosis, and prognostication. High-quality data with multidimensionality are needed for risk prediction, prognostication of specific clinical conditions, and their outcomes when using machine learning methods. Statement 5: Big data and cloud-based tools can help advance clinical research in gastroenterology. Multimodal data are key to understanding the maximal extent of the disease state and unlocking treatment options. Statement 6: Understanding how to evaluate AI algorithms in the gastroenterology literature and clinical trials is important for gastroenterologists, trainees, and researchers, and hence education efforts by GI societies are needed. Statement 7: Several challenges regarding integrating AI solutions into the clinical practice of endoscopy exist, including understanding the role of human-AI interaction. Transparency, interpretability, and explainability of AI algorithms play a key role in their clinical adoption in GI endoscopy. Developing appropriate AI governance, data procurement, and tools needed for the AI lifecycle are critical for the successful implementation of AI into clinical practice. Statement 8: For payment of AI in endoscopy, a thorough evaluation of the potential value proposition for AI systems may help guide purchasing decisions in endoscopy. Reliable cost-effectiveness studies to guide reimbursement are needed. Statement 9: Relevant clinical outcomes and performance metrics for AI in gastroenterology are currently not well defined. To improve the quality and interpretability of research in the field, steps need to be taken to define these evidence standards. Statement 10: A balanced view of AI technologies and active collaboration between the medical technology industry, computer scientists, gastroenterologists, and researchers are critical for the meaningful advancement of AI in gastroenterology., Conclusions: The consensus process led by the ASGE AI Task Force and experts from various disciplines has shed light on the potential of AI in endoscopy and gastroenterology. AI-based algorithms have shown promise in augmenting endoscopist performance, redefining quality metrics, optimizing workflows, and aiding in predictive modeling and diagnosis. However, challenges remain in evaluating AI algorithms, ensuring transparency and interpretability, addressing governance and data procurement, determining payment models, defining relevant clinical outcomes, and fostering collaboration between stakeholders. Addressing these challenges while maintaining a balanced perspective is crucial for the meaningful advancement of AI in gastroenterology., Competing Interests: Disclosure The following authors disclosed financial relationships: S. Parasa: Consultant for Medtronic and Microsoft Research; advisory board for the Allen Institute for Artificial Intelligence and Fujifilm; research support from Fujifilm. T. Berzin: Consultant for Medtronic, Wision AI, Magentiq Eye, RSIP Vision, and Docbot AI. C. Leggett: Consultant for Verily Life Sciences. S. Gross: Consultant for Medtronic and Iterative Scopes. A. Repici: Research support from Fujifilm, Boston Scientific Corporation, and Norgine; speaker for Boston Scientific Corporation and Norgine. O. F. Ahmad: Speaker for Olympus Corporation and Medtronic. A. Chiang: Employee at Medtronic. N. Coelho-Prabhu: Scientific advisory board for Iterative Health. J. Cohen: Consultant for Olympus and Micro-Tech; stock in GI Windows, Virtual Health Partners, and Rom-Tech; owner of MD Medical Navigators. E. Dekker: Research support from Fujifilm; consultant for Fujifilm, Olympus, Ambu, and InterVenn; speaker for Olympus, Fujifilm, GI Supply, IPSEN, PAION, and Norgine. R. N. Keswani: Consultant for Boston Scientific Corporation and Medtronic. C. E. Kahn: Travel compensation from Sectra USA; advisory council for Epic Corporation. C. Hassan: Consultant for Odin, Fujifilm, Olympus, and NEC. P. Mountney: Employment relationship with Odin Medical Limited and Olympus Medical. J. Ng: Chief executive officer and founder of Iterative Health. Y. Mori: Consultant for Olympus; speaker for Olympus; device loan from Olympus; royalties from Cybernet System. S. Thakkar: Consultant for Boston Scientific Corporation and Medtronic; advisor for Iterative Scopes. I. Waxman: Consultant for Medtronic, BSCI, and Cook Medical; advisory board for Magentiq Eye. M. B. Wallace: Consultant for Boston Scientific Corporation, Cosmo/Aries Pharmaceuticals, Verily, Endiatix, Intervenn, AlphaMed UAE, Fujifilm, and ClearNote; research support from Cosmo/Aries Pharmaceuticals and Boston Scientific Corporation; independent contractor for Olympus, Medtronic, and Ninepoint Medical; stock in Virgo Inc. P. Sharma: Consultant for Bausch, Boston Scientific Corporation, CDx Labs, Covidien LP, Exact Sciences, Fujifilm Medical Systems USA, Inc, Lucid, Lumendi, Medtronic, Olympus America, Inc, and Salix; research support from Cosmo Pharmaceuticals, Covidien, Docbot, Erbe USA Inc, Fujifilm Holdings America Corporation, Ironwood Pharmaceuticals, Inc, Medtronic USA, Inc, Olympus, Salix, and US Endoscopy. All other authors disclosed no financial relationships., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

In 2020, Novartis Pharmaceuticals Corporation and the U.S. Food and Drug Administration (FDA) started a 4-year scientific collaboration to approach complex new data modalities and advanced analytics. The scientific question was to find novel radio-genomics-based prognostic and predictive factors for HR+/HER- metastatic breast cancer under a Research Collaboration Agreement. This collaboration has been providing valuable insights to help successfully implement future scientific projects, particularly using artificial intelligence and machine learning. This tutorial aims to provide tangible guidelines for a multi-omics project that includes multidisciplinary expert teams, spanning across different institutions. We cover key ideas, such as "maintaining effective communication" and "following good data science practices," followed by the four steps of exploratory projects, namely (1) plan, (2) design, (3) develop, and (4) disseminate. We break each step into smaller concepts with strategies for implementation and provide illustrations from our collaboration to further give the readers actionable guidance., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The adoption of artificial intelligence (AI) tools in medicine poses challenges to existing clinical workflows. This commentary discusses the necessity of context-specific quality assurance (QA), emphasizing the need for robust QA measures with quality control (QC) procedures that encompass (1) acceptance testing (AT) before clinical use, (2) continuous QC monitoring, and (3) adequate user training. The discussion also covers essential components of AT and QA, illustrated with real-world examples. We also highlight what we see as the shared responsibility of manufacturers or vendors, regulators, healthcare systems, medical physicists, and clinicians to enact appropriate testing and oversight to ensure a safe and equitable transformation of medicine through AI., Competing Interests: U.M., A.S.-D., H.-P.C., R.K.S., D.V., H.G., N.P., B.S., Z.H., K.C., G.T., T.M.D., D.R., R.M., and L.H. have nothing to disclose. K.D. receives royalties from Hologic. Q.C. has received compensations from Carina Medical LLC, not related to this work, provides consulting services for Reflexion Medical, not related to this work. R.M.S. received royalties for patents or software licenses from iCAD, Philips, ScanMed, Translation Holdings, PingAn, and MGB, and received research support from PingAn through a Cooperative Research and Development Agreement, not related to this work. J.J.N. has received royalties from Hologic and from MEDIAN Technologies, through the University of Chicago licensing, not related to this work. H.Y. has received royalties from licensing fees to Hologic and Medians Technologies through the University of Chicago licensing, not related to this work. K.S. provides consulting services for Canon Medical, not related to this work. L.M. has received funding from HealthTriagesrl, not related to this work. H.H. has received funding from Siemens Healthineers for a scientific research project, not related to this work. SG.A. III has received royalties and licensing fees for computer-aided diagnosis through the University of Chicago Consultant, Novartis, not related to this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Purpose: Understanding an artificial intelligence (AI) model's ability to generalize to its target population is critical to ensuring the safe and effective usage of AI in medical devices. A traditional generalizability assessment relies on the availability of large, diverse datasets, which are difficult to obtain in many medical imaging applications. We present an approach for enhanced generalizability assessment by examining the decision space beyond the available testing data distribution., Approach: Vicinal distributions of virtual samples are generated by interpolating between triplets of test images. The generated virtual samples leverage the characteristics already in the test set, increasing the sample diversity while remaining close to the AI model's data manifold. We demonstrate the generalizability assessment approach on the non-clinical tasks of classifying patient sex, race, COVID status, and age group from chest x-rays., Results: Decision region composition analysis for generalizability indicated that a disproportionately large portion of the decision space belonged to a single "preferred" class for each task, despite comparable performance on the evaluation dataset. Evaluation using cross-reactivity and population shift strategies indicated a tendency to overpredict samples as belonging to the preferred class (e.g., COVID negative) for patients whose subgroup was not represented in the model development data., Conclusions: An analysis of an AI model's decision space has the potential to provide insight into model generalizability. Our approach uses the analysis of composition of the decision space to obtain an improved assessment of model generalizability in the case of limited test data., (© 2024 The Authors.)

Purpose: Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and atypical endometrial hyperplasia (AEH) is considered a high-risk precursor to EC. Hormone therapies and hysterectomy are practical treatment options for AEH and early-stage EC. Some patients prefer hormone therapies for reasons such as fertility preservation or being poor surgical candidates. However, accurate prediction of an individual patient's response to hormonal treatment would allow for personalized and potentially improved recommendations for these conditions. This study aims to explore the feasibility of using deep learning models on whole slide images (WSI) of endometrial tissue samples to predict the patient's response to hormonal treatment., Approach: We curated a clinical WSI dataset of 112 patients from two clinical sites. An expert pathologist annotated these images by outlining AEH/EC regions. We developed an end-to-end machine learning model with mixed supervision. The model is based on image patches extracted from pathologist-annotated AEH/EC regions. Either an unsupervised deep learning architecture (Autoencoder or ResNet50), or non-deep learning (radiomics feature extraction) is used to embed the images into a low-dimensional space, followed by fully connected layers for binary prediction, which was trained with binary responder/non-responder labels established by pathologists. We used stratified sampling to partition the dataset into a development set and a test set for internal validation of the performance of our models., Results: The autoencoder model yielded an AUROC of 0.80 with 95% CI [0.63, 0.95] on the independent test set for the task of predicting a patient with AEH/EC as a responder vs non-responder to hormonal treatment., Conclusions: These findings demonstrate the potential of using mixed supervised machine learning models on WSIs for predicting the response to hormonal treatment in AEH/EC patients., (© 2024 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: Bone health and fracture risk are known to be correlated with stiffness. Both micro-finite element analysis (μFEA) and mechanical testing of additive manufactured phantoms are useful approaches for estimating mechanical properties of trabecular bone-like structures. However, it is unclear if measurements from the two approaches are consistent. The purpose of this work is to evaluate the agreement between stiffness measurements obtained from mechanical testing of additive manufactured trabecular bone phantoms and μFEA modeling. Agreement between the two methods would suggest 3D printing is a viable method for validation of μFEA modeling., Methods: A set of 20 lumbar vertebrae regions of interests were segmented and the corresponding trabecular bone phantoms were produced using selective laser sintering. The phantoms were mechanically tested in uniaxial compression to derive their stiffness values. The stiffness values were also derived from in silico simulation, where linear elastic μFEA was applied to simulate the same compression and boundary conditions. Bland-Altman analysis was used to evaluate agreement between the mechanical testing and μFEA simulation values. Additionally, we evaluated the fidelity of the 3D printed phantoms as well as the repeatability of the 3D printing and mechanical testing process., Results: We observed good agreement between the mechanically tested stiffness and μFEA stiffness, with R 2 of 0.84 and normalized root mean square deviation of 8.1%. We demonstrate that the overall trabecular bone structures are printed in high fidelity (Dice score of 0.97 (95% CI, [0.96,0.98]) and that mechanical testing is repeatable (coefficient of variation less than 5% for stiffness values from testing of duplicated phantoms). However, we noticed some defects in the resin microstructure of the 3D printed phantoms, which may account for the discrepancy between the stiffness values from simulation and mechanical testing., Conclusion: Overall, the level of agreement achieved between the mechanical stiffness and μFEA indicates that our μFEA methods may be acceptable for assessing bone mechanics of complex trabecular structures as part of an analysis of overall bone health., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: To introduce developers to medical device regulatory processes and data considerations in artificial intelligence and machine learning (AI/ML) device submissions and to discuss ongoing AI/ML-related regulatory challenges and activities., Approach: AI/ML technologies are being used in an increasing number of medical imaging devices, and the fast evolution of these technologies presents novel regulatory challenges. We provide AI/ML developers with an introduction to U.S. Food and Drug Administration (FDA) regulatory concepts, processes, and fundamental assessments for a wide range of medical imaging AI/ML device types., Results: The device type for an AI/ML device and appropriate premarket regulatory pathway is based on the level of risk associated with the device and informed by both its technological characteristics and intended use. AI/ML device submissions contain a wide array of information and testing to facilitate the review process with the model description, data, nonclinical testing, and multi-reader multi-case testing being critical aspects of the AI/ML device review process for many AI/ML device submissions. The agency is also involved in AI/ML-related activities that support guidance document development, good machine learning practice development, AI/ML transparency, AI/ML regulatory research, and real-world performance assessment., Conclusion: FDA's AI/ML regulatory and scientific efforts support the joint goals of ensuring patients have access to safe and effective AI/ML devices over the entire device lifecycle and stimulating medical AI/ML innovation., (© 2023 The Authors.)

Endometrial cancer (EC) is the most common gynecologic malignancy in the US and complex atypical hyperplasia (CAH) is considered a high-risk precursor to EC. Treatment options for CAH and early-stage EC include hormone therapies and hysterectomy with the former preferred by certain patients, e.g., for fertility preservation or poor surgical candidates. Accurate prediction of response to hormonal treatment would allow for personalized and potentially improved recommendations for the treatment of these conditions. In this study, we investigate the feasibility of utilizing weakly supervised deep learning models on whole slide images of endometrial tissue samples for the prediction of patient response to hormonal treatment. We curated a clinical whole-slide-image (WSI) dataset of 112 patients from two clinical sites. We developed an end-to-end machine learning model using WSIs of endometrial specimens for the prediction of hormonal treatment response among women with CAH/EC. The model takes patches extracted from pathologist-annotated CAH/EC regions as input and utilizes an unsupervised deep learning architecture (Autoencoder or ResNet50) to embed the images into a low-dimensional space, followed by fully connected layers for binary prediction. Our autoencoder model yielded an AUC of 0.79 with 95% CI [0.61, 0.98] on a hold-out test set in the task of predicting a patient with CAH/EC as a responder vs non-responder to hormonal treatment. Our results, demonstrate the potential for using weakly supervised machine learning models on WSIs for predicting response to hormonal treatment of CAH/EC patients.

Importance: An accurate and robust artificial intelligence (AI) algorithm for detecting cancer in digital breast tomosynthesis (DBT) could significantly improve detection accuracy and reduce health care costs worldwide., Objectives: To make training and evaluation data for the development of AI algorithms for DBT analysis available, to develop well-defined benchmarks, and to create publicly available code for existing methods., Design, Setting, and Participants: This diagnostic study is based on a multi-institutional international grand challenge in which research teams developed algorithms to detect lesions in DBT. A data set of 22 032 reconstructed DBT volumes was made available to research teams. Phase 1, in which teams were provided 700 scans from the training set, 120 from the validation set, and 180 from the test set, took place from December 2020 to January 2021, and phase 2, in which teams were given the full data set, took place from May to July 2021., Main Outcomes and Measures: The overall performance was evaluated by mean sensitivity for biopsied lesions using only DBT volumes with biopsied lesions; ties were broken by including all DBT volumes., Results: A total of 8 teams participated in the challenge. The team with the highest mean sensitivity for biopsied lesions was the NYU B-Team, with 0.957 (95% CI, 0.924-0.984), and the second-place team, ZeDuS, had a mean sensitivity of 0.926 (95% CI, 0.881-0.964). When the results were aggregated, the mean sensitivity for all submitted algorithms was 0.879; for only those who participated in phase 2, it was 0.926., Conclusions and Relevance: In this diagnostic study, an international competition produced algorithms with high sensitivity for using AI to detect lesions on DBT images. A standardized performance benchmark for the detection task using publicly available clinical imaging data was released, with detailed descriptions and analyses of submitted algorithms accompanied by a public release of their predictions and code for selected methods. These resources will serve as a foundation for future research on computer-assisted diagnosis methods for DBT, significantly lowering the barrier of entry for new researchers.

Competing Interests: Competing interest statement: The authors do not have any competing interests to declare.

Purpose: Multiview two-dimensional (2D) convolutional neural networks (CNNs) and three-dimensional (3D) CNNs have been successfully used for analyzing volumetric data in many state-of-the-art medical imaging applications. We propose an alternative modular framework that analyzes volumetric data with an approach that is analogous to radiologists' interpretation, and apply the framework to reduce false positives that are generated in computer-aided detection (CADe) systems for pulmonary nodules in thoracic computed tomography (CT) scans., Methods: In our approach, a deep network consisting of 2D CNNs first processes slices individually. The features extracted in this stage are then passed to a recurrent neural network (RNN), thereby modeling consecutive slices as a sequence of temporal data and capturing the contextual information across all three dimensions in the volume of interest. Outputs of the RNN layer are weighed before the final fully connected layer, enabling the network to scale the importance of different slices within a volume of interest in an end-to-end training framework., Results: We validated the proposed architecture on the false positive reduction track of the lung nodule analysis (LUNA) challenge for pulmonary nodule detection in chest CT scans, and obtained competitive results compared to 3D CNNs. Our results show that the proposed approach can encode the 3D information in volumetric data effectively by achieving a sensitivity >0.8 with just 1/8 false positives per scan., Conclusions: Our experimental results demonstrate the effectiveness of temporal analysis of volumetric images for the application of false positive reduction in chest CT scans and show that state-of-the-art 2D architectures from the literature can be directly applied to analyzing volumetric medical data. As newer and better 2D architectures are being developed at a much faster rate compared to 3D architectures, our approach makes it easy to obtain state-of-the-art performance on volumetric data using new 2D architectures., (© 2020 American Association of Physicists in Medicine.)

Deep two-dimensional (2-D) convolutional neural networks (CNNs) have been remarkably successful in producing record-breaking results in a variety of computer vision tasks. It is possible to extend CNNs to three dimensions using 3-D kernels to make them suitable for volumetric medical imaging data such as CT or MRI, but this increases the processing time as well as the required number of training samples (due to the higher number of parameters that need to be learned). In this paper, we address both of these issues for a 3-D CNN implementation through the development of a two-stage computer-aided detection system for automatic detection of pulmonary nodules. The first stage consists of a 3-D fully convolutional network for fast screening and generation of candidate suspicious regions. The second stage consists of an ensemble of 3-D CNNs trained using extensive transformations applied to both the positive and negative patches to augment the training set. To enable the second stage classifiers to learn differently, they are trained on false positive patches obtained from the screening model using different thresholds on their associated scores as well as different augmentation types. The networks in the second stage are averaged together to produce the final classification score for each candidate patch. Using this procedure, our overall nodule detection system called DeepMed is fast and can achieve 91% sensitivity at 2 false positives per scan on cases from the LIDC dataset.

Advances in machine learning in medical imaging are occurring at a rapid pace in research laboratories both at academic institutions and in industry. Important artificial intelligence (AI) tools for diagnostic imaging include algorithms for disease detection and classification, image optimization, radiation reduction, and workflow enhancement. Although advances in foundational research are occurring rapidly, translation to routine clinical practice has been slower. In August 2018, the National Institutes of Health assembled multiple relevant stakeholders at a public meeting to discuss the current state of knowledge, infrastructure gaps, and challenges to wider implementation. The conclusions of that meeting are summarized in two publications that identify and prioritize initiatives to accelerate foundational and translational research in AI for medical imaging. This publication summarizes key priorities for translational research developed at the workshop including: (1) creating structured AI use cases, defining and highlighting clinical challenges potentially solvable by AI; (2) establishing methods to encourage data sharing for training and testing AI algorithms to promote generalizability to widespread clinical practice and mitigate unintended bias; (3) establishing tools for validation and performance monitoring of AI algorithms to facilitate regulatory approval; and (4) developing standards and common data elements for seamless integration of AI tools into existing clinical workflows. An important goal of the resulting road map is to grow an ecosystem, facilitated by professional societies, industry, and government agencies, that will allow robust collaborations between practicing clinicians and AI researchers to advance foundational and translational research relevant to medical imaging., (Copyright © 2019 American College of Radiology. All rights reserved.)

Rationale and Objectives: The quantitative assessment of volumetric CT for discriminating small changes in nodule size has been under-examined. This phantom study examined the effect of imaging protocol, nodule size, and measurement method on volume-based change discrimination across low and high object to background contrast tasks., Materials and Methods: Eight spherical objects ranging in diameter from 5.0 mm to 5.75 mm and 8.0 mm to 8.75 mm with 0.25 mm increments were scanned within an anthropomorphic phantom with either foam-background (high-contrast task, ∼1000 HU object to background difference)) or gelatin-background (low-contrast task, ∼50 to 100 HU difference). Ten repeat acquisitions were collected for each protocol with varying exposures, reconstructed slice thicknesses and reconstruction kernels. Volume measurements were obtained using a matched-filter approach (MF) and a publicly available 3D segmentation-based tool (SB). Discrimination of nodule sizes was assessed using the area under the ROC curve (AUC)., Results: Using a low-dose (1.3 mGy), thin-slice (≤1.5 mm) protocol, changes of 0.25 mm in diameter were detected with AU = 1.0 for all baseline sizes for the high-contrast task regardless of measurement method. For the more challenging low-contrast task and same protocol, MF detected changes of 0.25 mm from baseline sizes ≥5.25 mm and volume changes ≥9.4% with AUC≥0.81 whereas corresponding results for SB were poor (AUC within 0.49-0.60). Performance for SB was improved, but still inconsistent, when exposure was increased to 4.4 mGy., Conclusion: The reliable discrimination of small changes in pulmonary nodule size with low-dose, thin-slice CT protocols suitable for lung cancer screening was dependent on the inter-related effects of nodule to background contrast and measurement method., (Published by Elsevier Inc.)

Rationale and Objectives: To evaluate a new approach to establish compliance of segmentation tools with the computed tomography volumetry profile of the Quantitative Imaging Biomarker Alliance (QIBA); and determine the statistical exchangeability between real and simulated lesions through an international challenge., Materials and Methods: The study used an anthropomorphic phantom with 16 embedded physical lesions and 30 patient cases from the Reference Image Database to Evaluate Therapy Response with pathologically confirmed malignancies. Hybrid datasets were generated by virtually inserting simulated lesions corresponding to physical lesions into the phantom datasets using one projection-domain-based method (Method 1), two image-domain insertion methods (Methods 2 and 3), and simulated lesions corresponding to real lesions into the Reference Image Database to Evaluate Therapy Response dataset (using Method 2). The volumes of the real and simulated lesions were compared based on bias (measured mean volume differences between physical and virtually inserted lesions in phantoms as quantified by segmentation algorithms), repeatability, reproducibility, equivalence (phantom phase), and overall QIBA compliance (phantom and clinical phase)., Results: For phantom phase, three of eight groups were fully QIBA compliant, and one was marginally compliant. For compliant groups, the estimated biases were -1.8 ± 1.4%, -2.5 ± 1.1%, -3 ± 1%, -1.8 ± 1.5% (±95% confidence interval). No virtual insertion method showed statistical equivalence to physical insertion in bias equivalence testing using Schuirmann's two one-sided test (±5% equivalence margin). Differences in repeatability and reproducibility across physical and simulated lesions were largely comparable (0.1%-16% and 7%-18% differences, respectively). For clinical phase, 7 of 16 groups were QIBA compliant., Conclusion: Hybrid datasets yielded conclusions similar to real computed tomography datasets where phantom QIBA compliant was also compliant for hybrid datasets. Some groups deemed compliant for simulated methods, not for physical lesion measurements. The magnitude of this difference was small (<5.4%). While technical performance is not equivalent, they correlate, such that, volumetrically simulated lesions could potentially serve as practical proxies., (Copyright © 2018 The Association of University Radiologists. All rights reserved.)

We investigated effects of prevalence and case distribution on radiologist diagnostic performance as measured by area under the receiver operating characteristic curve (AUC) and sensitivity-specificity in lab-based reader studies evaluating imaging devices. Our retrospective reader studies compared full-field digital mammography (FFDM) to screen-film mammography (SFM) for women with dense breasts. Mammograms were acquired from the prospective Digital Mammographic Imaging Screening Trial. We performed five reader studies that differed in terms of cancer prevalence and the distribution of noncancers. Twenty radiologists participated in each reader study. Using split-plot study designs, we collected recall decisions and multilevel scores from the radiologists for calculating sensitivity, specificity, and AUC. Differences in reader-averaged AUCs slightly favored SFM over FFDM (biggest AUC difference: 0.047, SE = 0.023 , p = 0.047 ), where standard error accounts for reader and case variability. The differences were not significant at a level of 0.01 (0.05/5 reader studies). The differences in sensitivities and specificities were also indeterminate. Prevalence had little effect on AUC (largest difference: 0.02), whereas sensitivity increased and specificity decreased as prevalence increased. We found that AUC is robust to changes in prevalence, while radiologists were more aggressive with recall decisions as prevalence increased.

Extracting coronary artery calcium (CAC) scores from contrast-enhanced computed tomography (CT) images using dual-energy (DE) based material decomposition has been shown feasible, mainly through patient studies. However, the quantitative performance of such DE-based CAC scores, particularly per stenosis, is underexamined due to lack of reference standard and repeated scans. In this work we conducted a comprehensive quantitative comparative analysis of CAC scores obtained with DE and compare to conventional unenhanced single-energy (SE) CT scans through phantom studies. Synthetic vessels filled with iodinated blood mimicking material and containing calcium stenoses of different sizes and densities were scanned with a third generation dual-source CT scanner in a chest phantom using a DE coronary CT angiography protocol with three exposures/CTDIvol: auto-mAs/8 mGy (automatic exposure), 160 mAs/20 mGy and 260 mAs/34 mGy and 10 repeats. As a control, a set of vessel phantoms without iodine was scanned using a standard SE CAC score protocol (3 mGy). Calcium volume, mass and Agatston scores were estimated for each stenosis. For DE dataset, image-based three-material decomposition was applied to remove iodine before scoring. Performance of DE-based calcium scores were analyzed on a per-stenosis level and compared to SE-based scores. There was excellent correlation between the DE- and SE-based scores (correlation coefficient r: 0.92-0.98). Percent bias for the calcium volume and mass scores varied as a function of stenosis size and density for both modalities. Precision (coefficient of variation) improved with larger and denser stenoses for both DE- and SE-based calcium scores. DE-based scores (20 mGy and 34 mGy) provided comparable per-stenosis precision to SE-based (3 mGy). Our findings suggest that on a per-stenosis level, DE-based CAC scores from contrast-enhanced CT images can achieve comparable quantification performance to conventional SE-based scores. However, DE-based CAC scoring required more dose compared with SE for high per-stenosis precision so some caution is necessary with clinical DE-based CAC scoring.

Background: To assess the volumetric measurement of small (≤1 cm) nonsolid nodules with computed tomography (CT), focusing on the interaction of state of the art iterative reconstruction (IR) methods and dose with nodule densities, sizes, and shapes., Methods: Twelve synthetic nodules [5 and 10 mm in diameter, densities of -800, -630 and -10 Hounsfield units (HU), spherical and spiculated shapes] were scanned within an anthropomorphic phantom. Dose [computed tomography scan dose index (CTDI vol )] ranged from standard (4.1 mGy) to below screening levels (0.3 mGy). Data was reconstructed using filtered back-projection and two state-of-the-art IR methods (adaptive and model-based). Measurements were extracted with a previously validated matched filter-based estimator. Analysis of accuracy and precision was based on evaluation of percent bias (PB) and the repeatability coefficient (RC) respectively., Results: Density had the most important effect on measurement error followed by the interaction of density with nodule size. The nonsolid -630 HU nodules had high accuracy and precision at levels comparable to solid (-10 HU) nonsolid, regardless of reconstruction method and with CTDI vol as low as 0.6 mGy. PB was <5% and <11% for the 10- and 5-mm in nominal diameter -630 HU nodules respectively, and RC was <5% and <12% for the same nodules. For nonsolid -800 HU nodules, PB increased to <11% and <30% for the 10- and 5-mm nodules respectively, whereas RC increased slightly overall but varied widely across dose and reconstruction algorithms for the 5-mm nodules. Model-based IR improved measurement accuracy for the 5-mm, low-density (-800, -630 HU) nodules. For other nodules the effect of reconstruction method was small. Dose did not affect volumetric accuracy and only affected slightly the precision of 5-mm nonsolid nodules., Conclusions: Reasonable values of both accuracy and precision were achieved for volumetric measurements of all 10-mm nonsolid nodules, and for the 5-mm nodules with -630 HU or higher density, when derived from scans acquired with below screening dose levels as low as 0.6 mGy and regardless of reconstruction algorithm., Competing Interests: Conflicts of Interest: K Schultz is employed by Toshiba Medical Research Institute, Inc., USA (TMRU). Toshiba was responsible for performing the CT reconstructions from the Toshiba scanner. J Siegelman was partly funded by Toshiba through a research collaboration agreement and is currently employed by the Takeda Pharmaceutical Company.

The performance of a classifier is largely dependent on the size and representativeness of data used for its training. In circumstances where accumulation and/or labeling of training samples is difficult or expensive, such as medical applications, data augmentation can potentially be used to alleviate the limitations of small datasets. We have previously developed an image blending tool that allows users to modify or supplement an existing CT or mammography dataset by seamlessly inserting a lesion extracted from a source image into a target image. This tool also provides the option to apply various types of transformations to different properties of the lesion prior to its insertion into a new location. In this study, we used this tool to create synthetic samples that appear realistic in chest CT. We then augmented different size training sets with these artificial samples, and investigated the effect of the augmentation on training various classifiers for the detection of lung nodules. Our results indicate that the proposed lesion insertion method can improve classifier performance for small training datasets, and thereby help reduce the need to acquire and label actual patient data.

Deep convolutional neural networks (CNNs) form the backbone of many state-of-the-art computer vision systems for classification and segmentation of 2D images. The same principles and architectures can be extended to three dimensions to obtain 3D CNNs that are suitable for volumetric data such as CT scans. In this work, we train a 3D CNN for automatic detection of pulmonary nodules in chest CT images using volumes of interest extracted from the LIDC dataset. We then convert the 3D CNN which has a fixed field of view to a 3D fully convolutional network (FCN) which can generate the score map for the entire volume efficiently in a single pass. Compared to the sliding window approach for applying a CNN across the entire input volume, the FCN leads to a nearly 800-fold speed-up, and thereby fast generation of output scores for a single case. This screening FCN is used to generate difficult negative examples that are used to train a new discriminant CNN. The overall system consists of the screening FCN for fast generation of candidate regions of interest, followed by the discrimination CNN.

Rationale and Objectives: Different computed tomography imaging protocols and patient characteristics can impact the accuracy and precision of the calcium score and may lead to inconsistent patient treatment recommendations. The aim of this work was to determine the impact of reconstruction algorithm and gender characteristics on coronary artery calcium scoring based on a phantom study using computed tomography., Materials and Methods: Four synthetic heart vessels with vessel diameters corresponding to female and male left main and left circumflex arteries containing calcification-mimicking materials (200-1000 HU) were inserted into a thorax phantom and were scanned with and without female breast plates (male and female phantoms, respectively). Ten scans were acquired and were reconstructed at 3-mm slices using filtered-back projection (FBP) and iterative reconstruction with medium and strong denoising (IR3 and IR5) algorithms. Agatston and calcium volume scores were estimated for each vessel. Calcium scores for each vessel and the total calcium score (summation of all four vessels) were compared between the two phantoms to quantify the impact of the breast plates and reconstruction parameters. Calcium scores were also compared among vessels of different diameters to investigate the impact of the vessel size., Results: The calcium scores were significantly larger for FBP reconstruction (FBP > IR3>IR5). Agatston scores (calcium volume score) for vessels in the male phantom scans were on average 4.8% (2.9%), 8.2% (7.1%), and 10.5% (9.4%) higher compared to those in the female phantom with FBP, IR3, and IR5, respectively, when exposure was conserved across phantoms. The total calcium scores from the male phantom were significantly larger than those from the female phantom (P <0.05). In general, calcium volume scores were underestimated (up to about 50%) for smaller vessels, especially when scanned in the female phantom., Conclusions: Calcium scores significantly decreased with iterative reconstruction and tended to be underestimated for female anatomy (smaller vessels and presence of breast plates)., (Published by Elsevier Inc.)

Rationale and Objectives: Quantifying changes in lung tumor volume is important for diagnosis, therapy planning, and evaluation of response to therapy. The aim of this study was to assess the performance of multiple algorithms on a reference data set. The study was organized by the Quantitative Imaging Biomarker Alliance (QIBA)., Materials and Methods: The study was organized as a public challenge. Computed tomography scans of synthetic lung tumors in an anthropomorphic phantom were acquired by the Food and Drug Administration. Tumors varied in size, shape, and radiodensity. Participants applied their own semi-automated volume estimation algorithms that either did not allow or allowed post-segmentation correction (type 1 or 2, respectively). Statistical analysis of accuracy (percent bias) and precision (repeatability and reproducibility) was conducted across algorithms, as well as across nodule characteristics, slice thickness, and algorithm type., Results: Eighty-four percent of volume measurements of QIBA-compliant tumors were within 15% of the true volume, ranging from 66% to 93% across algorithms, compared to 61% of volume measurements for all tumors (ranging from 37% to 84%). Algorithm type did not affect bias substantially; however, it was an important factor in measurement precision. Algorithm precision was notably better as tumor size increased, worse for irregularly shaped tumors, and on the average better for type 1 algorithms. Over all nodules meeting the QIBA Profile, precision, as measured by the repeatability coefficient, was 9.0% compared to 18.4% overall., Conclusion: The results achieved in this study, using a heterogeneous set of measurement algorithms, support QIBA quantitative performance claims in terms of volume measurement repeatability for nodules meeting the QIBA Profile criteria., (Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

A major initiative of the Quantitative Imaging Biomarker Alliance is to develop standards-based documents called "Profiles," which describe one or more technical performance claims for a given imaging modality. The term "actor" denotes any entity (device, software, or person) whose performance must meet certain specifications for the claim to be met. The objective of this paper is to present the statistical issues in testing actors' conformance with the specifications. In particular, we present the general rationale and interpretation of the claims, the minimum requirements for testing whether an actor achieves the performance requirements, the study designs used for testing conformity, and the statistical analysis plan. We use three examples to illustrate the process: apparent diffusion coefficient in solid tumors measured by MRI, change in Perc 15 as a biomarker for the progression of emphysema, and percent change in solid tumor volume by computed tomography as a biomarker for lung cancer progression., (Copyright © 2016 The Association of University Radiologists. All rights reserved.)

Measurements of lung nodule volume with multi-detector computed tomography (MDCT) have been shown to be more accurate and precise compared to conventional lower dimensional measurements. Quantifying the size of lesions is potentially more difficult when the object-to-background contrast is low as with lesions in the liver. Physical phantom and simulation studies are often utilized to analyze the bias and variance of lesion size estimates because a ground truth or reference standard can be established. In addition, it may also be useful to derive theoretical bounds as another way of characterizing lesion sizing methods. The goal of this work was to study the performance of a MDCT system for a lesion volume estimation task with object-to-background contrast less than 50 HU, and to understand the relation among performances obtained from phantom study, simulation and theoretical analysis. We performed both phantom and simulation studies, and analyzed the bias and variance of volume measurements estimated by a matched-filter-based estimator. We further corroborated results with a theoretical analysis to estimate the achievable performance bound, which was the Cramer-Rao's lower bound (CRLB) of minimum variance for the size estimates. Results showed that estimates of non-attached solid small lesion volumes with object-to-background contrast of 31-46 HU can be accurate and precise, with less than 10.8% in percent bias and 4.8% in standard deviation of percent error (SPE), in standard dose scans. These results are consistent with theoretical (CRLB), computational (simulation) and empirical phantom bounds. The difference between the bounds is rather small (for SPE less than 1.9%) indicating that the theoretical- and simulation-based performance bounds can be good surrogates for physical phantom studies.

Purpose: To assess the diagnostic performance of distributed human intelligence for the classification of polyp candidates identified with computer-aided detection (CAD) for computed tomographic (CT) colonography., Materials and Methods: This study was approved by the institutional Office of Human Subjects Research. The requirement for informed consent was waived for this HIPAA-compliant study. CT images from 24 patients, each with at least one polyp of 6 mm or larger, were analyzed by using CAD software to identify 268 polyp candidates. Twenty knowledge workers (KWs) from a crowdsourcing platform labeled each polyp candidate as a true or false polyp. Two trials involving 228 KWs were conducted to assess reproducibility. Performance was assessed by comparing the area under the receiver operating characteristic curve (AUC) of KWs with the AUC of CAD for polyp classification., Results: The detection-level AUC for KWs was 0.845 ± 0.045 (standard error) in trial 1 and 0.855 ± 0.044 in trial 2. These were not significantly different from the AUC for CAD, which was 0.859 ± 0.043. When polyp candidates were stratified by difficulty, KWs performed better than CAD on easy detections; AUCs were 0.951 ± 0.032 in trial 1, 0.966 ± 0.027 in trial 2, and 0.877 ± 0.048 for CAD (P = .039 for trial 2). KWs who participated in both trials showed a significant improvement in performance going from trial 1 to trial 2; AUCs were 0.759 ± 0.052 in trial 1 and 0.839 ± 0.046 in trial 2 (P = .041)., Conclusion: The performance of distributed human intelligence is not significantly different from that of CAD for colonic polyp classification., (© RSNA.)

Multi-slice computed tomography (MSCT) scanners have become popular volumetric imaging tools. Deterministic and random properties of the resulting CT scans have been studied in the literature. Due to the large number of voxels in the three-dimensional (3D) volumetric dataset, full characterization of the noise covariance in MSCT scans is difficult to tackle. However, as usage of such datasets for quantitative disease diagnosis grows, so does the importance of understanding the noise properties because of their effect on the accuracy of the clinical outcome. The goal of this work is to study noise covariance in the helical MSCT volumetric dataset. We explore possible approximations to the noise covariance matrix with reduced degrees of freedom, including voxel-based variance, one-dimensional (1D) correlation, two-dimensional (2D) in-plane correlation and the noise power spectrum (NPS). We further examine the effect of various noise covariance models on the accuracy of a prewhitening matched filter nodule size estimation strategy. Our simulation results suggest that the 1D longitudinal, 2D in-plane and NPS prewhitening approaches can improve the performance of nodule size estimation algorithms. When taking into account computational costs in determining noise characterizations, the NPS model may be the most efficient approximation to the MSCT noise covariance matrix.

Purpose: The development of computer-aided diagnostic (CAD) methods for lung nodule detection, classification, and quantitative assessment can be facilitated through a well-characterized repository of computed tomography (CT) scans. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI) completed such a database, establishing a publicly available reference for the medical imaging research community. Initiated by the National Cancer Institute (NCI), further advanced by the Foundation for the National Institutes of Health (FNIH), and accompanied by the Food and Drug Administration (FDA) through active participation, this public-private partnership demonstrates the success of a consortium founded on a consensus-based process., Methods: Seven academic centers and eight medical imaging companies collaborated to identify, address, and resolve challenging organizational, technical, and clinical issues to provide a solid foundation for a robust database. The LIDC/IDRI Database contains 1018 cases, each of which includes images from a clinical thoracic CT scan and an associated XML file that records the results of a two-phase image annotation process performed by four experienced thoracic radiologists. In the initial blinded-read phase, each radiologist independently reviewed each CT scan and marked lesions belonging to one of three categories ("nodule > or =3 mm," "nodule <3 mm," and "non-nodule > or =3 mm"). In the subsequent unblinded-read phase, each radiologist independently reviewed their own marks along with the anonymized marks of the three other radiologists to render a final opinion. The goal of this process was to identify as completely as possible all lung nodules in each CT scan without requiring forced consensus., Results: The Database contains 7371 lesions marked "nodule" by at least one radiologist. 2669 of these lesions were marked "nodule > or =3 mm" by at least one radiologist, of which 928 (34.7%) received such marks from all four radiologists. These 2669 lesions include nodule outlines and subjective nodule characteristic ratings., Conclusions: The LIDC/IDRI Database is expected to provide an essential medical imaging research resource to spur CAD development, validation, and dissemination in clinical practice.

A number of interrelated factors can affect the precision and accuracy of lung nodule size estimation. To quantify the effect of these factors, we have been conducting phantom CT studies using an anthropomorphic thoracic phantom containing a vasculature insert to which synthetic nodules were inserted or attached. Ten repeat scans were acquired on different multi-detector scanners, using several sets of acquisition and reconstruction protocols and various nodule characteristics (size, shape, density, location). This study design enables both bias and variance analysis for the nodule size estimation task. The resulting database is in the process of becoming publicly available as a resource to facilitate the assessment of lung nodule size estimation methodologies and to enable comparisons between different methods regarding measurement error. This resource complements public databases of clinical data and will contribute towards the development of procedures that will maximize the utility of CT imaging for lung cancer screening and tumor therapy evaluation.

A multiobjective genetic algorithm is designed to optimize a computer-aided detection (CAD) system for identifying colonic polyps. Colonic polyps appear as elliptical protrusions on the inner surface of the colon. Curvature-based features for colonic polyp detection have proved to be successful in several CT colonography (CTC) CAD systems. Our CTC CAD program uses a sequential classifier to form initial polyp detections on the colon surface. The classifier utilizes a set of thresholds on curvature-based features to cluster suspicious colon surface regions into polyp candidates. The thresholds were previously chosen experimentally by using feature histograms. The chosen thresholds were effective for detecting polyps sized 10 mm or larger in diameter. However, many medium-sized polyps, 6-9 mm in diameter, were missed in the initial detection procedure. In this paper, the task of finding optimal thresholds as a multiobjective optimization problem was formulated, and a genetic algorithm to solve it was utilized by evolving the Pareto front of the Pareto optimal set. The new CTC CAD system was tested on 792 patients. The sensitivities of the optimized system improved significantly, from 61.68% to 74.71% with an increase of 13.03% (95% CI [6.57%, 19.5%], p = 7.78 x 10(-5)) for the size category of 6-9 mm polyps, from 65.02% to 77.4% with an increase of 12.38% (95% CI [6.23%, 18.53%], p = 7.95 x 10(-5)) for polyps 6 mm or larger, and from 82.2% to 90.58% with an increase of 8.38% (95% CI [0.75%, 16%], p = 0.03) for polyps 8 mm or larger at comparable false positive rates. The sensitivities of the optimized system are nearly equivalent to those of expert radiologists.

In this paper, we propose an automated method for colon registration from supine and prone scans. Four anatomical salient points on the colon are distinguished first. Then correlation optimized warping (COW) method is applied to the segments defined by the anatomical landmarks to find better global registration based on local correlation of segments. To utilize more features along the colon centerline, we extended the COW method by embedding canonical correlation analysis into it for correlation calculation of colon segments. To verify the effectiveness of the proposed method, we tested the algorithm on a CTC dataset of 19 patients with 23 polyps. Experimental results show that by using our method, the estimation error of polyp location could be reduced 68.5% (from 41.6mm to 13.1mm on average) compared to a traditional dynamic warping algorithm.