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Diagnostic systems designed to detect possibly multiple lesions per patient (e.g. multiple polyps during CT colonoscopy) are often evaluated in "free-response" studies that allow for diagnostic responses unconstrained in their number and locations. Analysis of free-response studies requires extensions of the traditional receiver operating characteristic (ROC) analysis, which are termed free-response ROC (FROC) methodology. Despite substantial developments in this area, FROC tools and approaches are much more cumbersome than traditional ROC methods. Alternative approaches that use well-known ROC tools (e.g. ROI-ROC) require defining and physically delineating regions of interest (ROI) and combine FROC data within ROIs. We propose an approach that allows analyzing FROC data using conventional ROC tools without delineating the actual ROIs or reducing data. The design parameters of FROC study are used to make FROC data analyzable using ROC tools and to calibrate the corresponding FROC and ROC curves on both conceptual and numerical levels. Differences in the performance indices of the nonparametric FROC and the new approach are shown to be asymptotically negligible and typically rather small in practice. Data from a large multi-reader study of colon cancer detection are used to illustrate the new approach.

OBJECTIVE. The purpose of this study was to test the hypothesis whether two-view wide-angle digital breast tomosynthesis (DBT) can replace full-field digital mammography (FFDM) for breast cancer detection. SUBJECTS AND METHODS. In a multireader multicase study, bilateral two-view FFDM and bilateral two-view wide-angle DBT images were independently viewed for breast cancer detection in two reading sessions separated by more than 1 month. From a pool of 764 patients undergoing screening and diagnostic mammography, 330 patient-cases were selected. The endpoints were the mean ROC AUC for the reader per breast (breast level), ROC AUC per patient (subject level), noncancer recall rates, sensitivity, and specificity. RESULTS. Twenty-nine of 31 readers performed better with DBT than FFDM regardless of breast density. There was a statistically significant improvement in readers' mean diagnostic accuracy with DBT. The subject-level AUC increased from 0.765 (standard error [SE], 0.027) for FFDM to 0.835 (SE, 0.027) for DBT ( p = 0.002). Breast-level AUC increased from 0.818 (SE, 0.019) for FFDM to 0.861 (SE, 0.019) for DBT ( p = 0.011). The noncancer recall rate per patient was reduced by 19% with DBT ( p < 0.001). Masses and architectural distortions were detected more with DBT ( p < 0.001); calcifications trended lower ( p = 0.136). Accuracy for detection of invasive cancers was significantly greater with DBT ( p < 0.001). CONCLUSION. Reader performance in breast cancer detection is significantly higher with wide-angle two-view DBT independent of FFDM, verifying the robustness of DBT as a sole view. However, results of perception studies in the vision sciences support the inclusion of an overview image.

Physiological properties of tumors can be measured both in vivo and noninvasively by diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging. Although these techniques have been used for more than two decades to study tumor diffusion, perfusion, and/or permeability, the methods and studies on how to reduce measurement error and bias in the derived imaging metrics is still lacking in the literature. This is of paramount importance because the objective is to translate these quantitative imaging biomarkers (QIBs) into clinical trials, and ultimately in clinical practice. Standardization of the image acquisition using appropriate phantoms is the first step from a technical performance standpoint. The next step is to assess whether the imaging metrics have clinical value and meet the requirements for being a QIB as defined by the Radiological Society of North America's Quantitative Imaging Biomarkers Alliance (QIBA). The goal and mission of QIBA and the National Cancer Institute Quantitative Imaging Network (QIN) initiatives are to provide technical performance standards (QIBA profiles) and QIN tools for producing reliable QIBs for use in the clinical imaging community. Some of QIBA's development of quantitative diffusion-weighted imaging and dynamic contrast-enhanced QIB profiles has been hampered by the lack of literature for repeatability and reproducibility of the derived QIBs. The available research on this topic is scant and is not in sync with improvements or upgrades in MRI technology over the years. This review focuses on the need for QIBs in oncology applications and emphasizes the importance of the assessment of their reproducibility and repeatability. Level of Evidence: 5 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;49:e101-e121., (© 2018 International Society for Magnetic Resonance in Medicine.)

The aim of this study was to establish the repeatability measures of quantitative Gaussian and non-Gaussian diffusion metrics using diffusion-weighted imaging (DWI) data from phantoms and patients with head-and-neck and papillary thyroid cancers. The Quantitative Imaging Biomarker Alliance (QIBA) DWI phantom and a novel isotropic diffusion kurtosis imaging phantom were scanned at 3 different sites, on 1.5T and 3T magnetic resonance imaging systems, using standardized multiple b-value DWI acquisition protocol. In the clinical component of this study, a total of 60 multiple b-value DWI data sets were analyzed for test-retest, obtained from 14 patients (9 head-and-neck squamous cell carcinoma and 5 papillary thyroid cancers). Repeatability of quantitative DWI measurements was assessed by within-subject coefficient of variation (wCV%) and Bland-Altman analysis. In isotropic diffusion kurtosis imaging phantom vial with 2% ceteryl alcohol and behentrimonium chloride solution, the mean apparent diffusion (D app × 10 -3 mm 2 /s) and kurtosis (K app , unitless) coefficient values were 1.02 and 1.68 respectively, capturing in vivo tumor cellularity and tissue microstructure. For the same vial, D app and K app mean wCVs (%) were ≤1.41% and ≤0.43% for 1.5T and 3T across 3 sites. For pretreatment head-and-neck squamous cell carcinoma, apparent diffusion coefficient, D, D*, K, and f mean wCVs (%) were 2.38%, 3.55%, 3.88%, 8.0%, and 9.92%, respectively; wCVs exhibited a higher trend for papillary thyroid cancers. Knowledge of technical precision and bias of quantitative imaging metrics enables investigators to properly design and power clinical trials and better discern between measurement variability versus biological change.

As imaging technologies and treatment options continue to advance, imaging outcome measures are becoming increasingly utilized as the basis of making major decisions in new drug development and clinical practice. Quantitative imaging biomarkers (QIBs) are now commonly used for subject selection, response assessment, and safety monitoring. Although quantitative measurements can have many advantages compared with subjective, qualitative endpoints, it is important to recognize that QIBs are measured with error. This study uses Monte Carlo simulation to examine the impact of measurement error on a variety of clinical trial designs as well as to test proposed adjustments for measurement error. The focus is on some of the QIBs currently being studied by the Quantitative Imaging Biomarkers Alliance. The results show that the ability of QIBs to discriminate between health states and predict patient outcome is attenuated by measurement error; however, the known technical performance characteristics of QIBs can be used to adjust study sample size, control the misinterpretation rate of imaging findings, and establish statistically valid decision thresholds. We conclude that estimates of the precision and bias of a QIB are important for properly designing clinical trials and establishing the level of imaging standardization required.

Background The prognostic impact of jeopardized myocardium ( JM ) in patients with advanced ischemic cardiomyopathy ( ICM ) is unclear. We hypothesized that JM is an independent predictor of mortality in patients with advanced ICM . Methods and Results Patients with ICM who underwent cardiac magnetic resonance imaging between January 2002 and January 2013 were included in our study. JM was identified as a vascular territory with <50% myocardial scarring on cardiac magnetic resonance imaging and with >70% stenosis in a major coronary vessel that was not subsequently revascularized. A propensity score was developed for revascularization. A multivariable Cox proportional hazards model was used to evaluate the association of JM with all-cause mortality. We evaluated 631 patients over a mean follow-up of 5.1 years. Overall, 336 patients underwent subsequent revascularization during the follow-up period, among whom 23% had remaining JM , while 295 patients were medically treated (57% with JM ). There were 204 deaths (32%). On multivariable analysis, JM (hazard ratio, 1.88; 95% confidence interval, 1.38-2.55 [ P<0.001]) was independently associated with all-cause mortality after adjusting for multiple other factors. The risk associated with the presence of JM increased by 5% for every 10-unit increase in left ventricular end-systolic volume index. Conclusions JM is an independent and incremental predictor of mortality in patients with advanced ICM . Patients undergoing revascularization with residual JM had similar risk of mortality compared with medically treated patients with JM . The risk associated with JM significantly increased in the presence of worsening adverse left ventricular remodeling. Cardiac magnetic resonance viability assessment may provide important risk stratification in patients with ICM .

Background: Current decisions on cellular therapies for osteoarthritis are based primarily on clinical experience or on assumptions about preferred cell sourcing. They have not been informed by rigorous standardized measurements of the chondrogenic connective-tissue progenitors (CTP-Cs) or their intrinsic diversity of chondrogenic potential. The goal of this study was to quantitatively define the CTP-Cs resident in cartilage of different grades of osteoarthritis and to compare their concentration, prevalence, and biological potential., Methods: Twenty-three patients who had varus malalignment of the knee and were scheduled to undergo elective total knee arthroplasty for idiopathic osteoarthritis and who had grade 1-2 osteoarthritis on the lateral femoral condyle and grade 3-4 osteoarthritis on the medial femoral condyle were recruited for study of the cartilage removed during surgery. CTP-Cs were assayed by a standardized colony-forming-unit assay using automated image-analysis software based on ASTM standard test method F2944-12., Results: Cell concentration was significantly greater (p < 0.001) in grade 3-4 cartilage than in grade 1-2 cartilage. The prevalence of CTP-Cs varied widely, but it trended lower in grade 3-4 cartilage than in grade 1-2 samples (p = 0.078). The biological performance of CTP-Cs from grade 1-2 and grade 3-4 cartilage was comparable. Increased cell concentration was a significant predictor of decreased CTP-C prevalence (p = 0.002)., Conclusions: Although grade 3-4 cartilage showed fewer CTP-Cs than grade 1-2 cartilage, the range of biological performance was comparable, which suggests that either may be used as a source for potent CTP-Cs. However, the biological reason for the heterogeneity of CTP-Cs in cartilage and the biological implications of that heterogeneity are not well understood and require further study., Clinical Relevance: In order to improve the efficacy of cartilage cell therapy procedures, it is key to characterize the quality and quantity of the cells and progenitors being administered. Additionally, understanding the heterogeneity in order to select appropriate subsets of populations will improve the rigor of decisions concerning cell sourcing and targeting for pharmacological and cellular therapies.

Introduction Quantitative imaging biomarkers (QIBs) are being increasingly used in medical practice and clinical trials. An essential first step in the adoption of a quantitative imaging biomarker is the characterization of its technical performance, i.e. precision and bias, through one or more performance studies. Then, given the technical performance, a confidence interval for a new patient's true biomarker value can be constructed. Estimating bias and precision can be problematic because rarely are both estimated in the same study, precision studies are usually quite small, and bias cannot be measured when there is no reference standard. Methods A Monte Carlo simulation study was conducted to assess factors affecting nominal coverage of confidence intervals for a new patient's quantitative imaging biomarker measurement and for change in the quantitative imaging biomarker over time. Factors considered include sample size for estimating bias and precision, effect of fixed and non-proportional bias, clustered data, and absence of a reference standard. Results Technical performance studies of a quantitative imaging biomarker should include at least 35 test-retest subjects to estimate precision and 65 cases to estimate bias. Confidence intervals for a new patient's quantitative imaging biomarker measurement constructed under the no-bias assumption provide nominal coverage as long as the fixed bias is <12%. For confidence intervals of the true change over time, linearity must hold and the slope of the regression of the measurements vs. true values should be between 0.95 and 1.05. The regression slope can be assessed adequately as long as fixed multiples of the measurand can be generated. Even small non-proportional bias greatly reduces confidence interval coverage. Multiple lesions in the same subject can be treated as independent when estimating precision. Conclusion Technical performance studies of quantitative imaging biomarkers require moderate sample sizes in order to provide robust estimates of bias and precision for constructing confidence intervals for new patients. Assumptions of linearity and non-proportional bias should be assessed thoroughly.

Study Design: Cross-sectional analysis., Objectives: Given the lack of strong evidence/guidelines on appropriate treatment for lumbar spine disease, substantial variability exists among surgical treatments utilized, which is associated with differences in costs to treat a given pathology. Our goal was to investigate the variability in costs among spine surgeons nationally for the same pathology in similar patients., Methods: Four hundred forty-five spine surgeons completed a survey of clinical and radiographic case scenarios on patients with recurrent lumbar disc herniation, low back pain, and spondylolisthesis. Those surveyed were asked to provide various details including their geographical location, specialty, and fellowship training. Treatment options included no surgery, anterior lumbar interbody fusion, posterolateral fusion, and transforaminal/posterior lumbar interbody fusion. Costs were estimated via Medicare national payment amounts., Results: For recurrent lumbar disc herniation, no difference in costs existed for patients undergoing their first revision microdiscectomy. However, for patients undergoing another microdiscectomy, surgeons who operated <100 times/year had significantly lower costs than those who operated >200 times/year ( P < .001) and those with 5-15 years of experience had significantly higher costs than those with >15 years ( P < .001). For the treatment of low back pain, academic surgeons kept costs about 55% lower than private practice surgeons ( P < .001). In the treatment of spondylolisthesis, there was significant treatment variability without significant differences in costs., Conclusions: Significant variability in surgical treatment paradigms exists for different pathologies. Understanding why variability in treatment selection exists in similar clinical contexts across practices is important to ensure the most cost-effective delivery of care among spine surgeons., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cell-based therapies development for the treatment of osteoarthritis (OA) requires an understanding of the disease progression and attributes of the cells resident in cartilage. This study focused on quantitative assessment of the concentration and biological potential of stem and progenitor cells resident in different zones of cartilage displaying macroscopic Outerbridge grade 1-2 OA, and their correlation with OA progression based on established histologic scoring system. Lateral femoral condyles were collected from 15 patients with idiopathic OA and varus knees undergoing total knee arthroplasty. Superficial(C sp , top ∼ 500 µm) and deep cartilage(C dp ) was separated. Chondrogenic Connective Tissue Progenitors (CTP-C) were assayed by standardized Colony-Forming-Unit assay using automated image analysis (Colonyze TM ) based on ASTM standard F-2944-12. Cell concentration (cells/mg) was significantly greater in C sp (median: 7,000; range: 3,440-17,600) than C dp (median: 5,340; range: 3,393-9,660), p = 0.039. Prevalence (CTPs/million cells) was not different between C sp (median: 1,274; range: 0-3,898) and C dp (median:1,365; range:0-6,330), p = 0.42. In vitro performance of CTP-C progeny varied widely within and between patients, manifest by variation in colony size and morphology. Mean histopathological Mankin score was 4.7 (SD = 1.2), representing mild to moderate OA. Tidemark breach by blood vessels was associated with lower C sp cell concentration (p = 0.02). Matrix degradation was associated with lower C dp cell and CTP-C concentration (p = 0.015 and p = 0.095, respectively), independent of articular surface changes. These findings suggest that the initiation of OA may occur in either superficial or deep zones. The pathological changes affect CTP-Cs in C sp and C dp cartilage zones differently. The heterogeneity among the available CTP-Cs in C sp and C dp suggests performance-based selection to optimize cell-sourcing strategies for therapy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1728-1738, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background and purpose - A better understanding of the patterns and variation in initiation and progression of osteoarthritis (OA) in the knee may influence the design of therapies to prevent or slow disease progression. By studying cartilage from the human lateral femoral condyle (LFC), we aimed to: (1) assess specimen distribution into early, mild, moderate, and severe OA as per the established histopathological scoring systems (HHGS and OARSI); and (2) evaluate whether these 2 scoring systems provide sufficient tools for characterizing all the features and variation in patterns of OA. Patients and methods - 2 LFC osteochondral specimens (4 x 4 x 8 mm) were collected from 50 patients with idiopathic OA varus knee and radiographically preserved lateral compartment joint space undergoing total knee arthroplasty. These were fixed, sectioned, and stained with HE and Safranin O-Fast Green (SafO). Results - The histopathological OA severity distribution of the 100 specimens was: 6 early, 62 mild, 30 moderate, and 2 severe. Overall, 45/100 specimens were successfully scored by both HHGS and OARSI: 12 displayed low OA score and 33 displayed cartilage surface changes associated with other histopathological features. However, 55/100 samples exhibited low surface structure scores, but were deemed to be inadequately scored by HHGS and OARSI because of anomalous features in the deeper zones not accounted for by these systems: 27 exhibited both SafO and tidemark abnormal features, 16 exhibited only SafO abnormal features, and 12 exhibited tidemark abnormal features. Interpretation - LFC specimens were scored as mild to moderate OA by HHGS and OARSI. Yet, several specimens exhibited deep zone anomalies while maintaining good surface structure, inconsistent with mild OA. Overall, a better classification of these anomalous histopathological features could help better understand idiopathic OA and potentially recognize different subgroups of disease.

Receiver operating characteristic (ROC) analysis is a tool used to describe the discrimination accuracy of a diagnostic test or prediction model. While sensitivity and specificity are the basic metrics of accuracy, they have many limitations when characterizing test accuracy, particularly when comparing the accuracies of competing tests. In this article we review the basic study design features of ROC studies, illustrate sample size calculations, present statistical methods for measuring and comparing accuracy, and highlight commonly used ROC software. We include descriptions of multi-reader ROC study design and analysis, address frequently seen problems of verification and location bias, discuss clustered data, and provide strategies for testing endpoints in ROC studies. The methods are illustrated with a study of transmission ultrasound for diagnosing breast lesions.

Purpose To compare the diagnostic yield and complication rates of electromagnetic navigational bronchoscopic (ENB)-guided and computed tomography (CT)-guided percutaneous tissue sampling of lung nodules. Materials and Methods Retrospectively identified were 149 patients sampled percutaneously with CT guidance and 146 patients who underwent ENB with transbronchial biopsy of a lung lesion between 2013 and 2015. Clinical data, incidence of complications, and nodule pathologic analyses were assessed through electronic medical record review. Lung nodule characteristics were reviewed through direct image analysis. Molecular marker studies and pathologic analyses from surgical excision were reviewed when available. Multiple-variable logistic regression models were built to compare the diagnostic yield and complication rates for each method and for different patient and disease characteristics. Results CT-guided sampling was more likely to be diagnostic than ENB-guided biopsy (86.0% [129 of 150] vs 66.0% [99 of 150], respectively), and this difference remained significant even after adjustments were made for patient and nodule characteristics (P < .001). Age, American Society of Anesthesiologists class, emphysema grade, nodule size, and distance from pleura were not significant predictors of increased diagnostic yield. Intraprocedural time for physicians was significantly lower with CT-guided sampling (P < .001). Similar yield for molecular analyses was noted with the two approaches (ENB-guided sampling, 88.9% [32 of 36]; CT-guided sampling, 82.0% [41 of 50]). The two groups had similar rates of major complications (symptomatic hemorrhage, P > .999; pneumothorax requiring chest tube and/or admission, P = .417). Conclusion CT-guided transthoracic biopsy provided higher diagnostic yield in the assessment of peripheral pulmonary nodules than navigational bronchoscopy with a similar rate of clinically relevant complications. © RSNA, 2017 Online supplemental material is available for this article.

Background: We sought to determine whether there are ultrasound parameters that differ between knees with symptomatic fat pad synovial impingement and asymptomatic knees., Methods: A prospective study was performed in patients with clinical signs and symptoms of fat pad synovial impingement and asymptomatic controls. Eleven symptomatic knees and 10 asymptomatic controls were evaluated. Ultrasound imaging was performed before and after exercise. Evaluated parameters included largest fat lobule compressibility, subjective assessment of vascularity, largest vessel diameter, and subjective assessment of dynamic fat pad motion during flexion and extension. Receiver operating characteristic (ROC) curve analysis was used to assess whether changes in these parameters were different between symptomatic and asymptomatic knees., Results: Change in the largest vessel diameter was greater and trended toward dilation in asymptomatic knees compared to symptomatic knees (mean: 0.83 vs. -0.02; P<0.001). No significant differences were observed between symptomatic and asymptomatic knees with respect to pre-exercise versus post-exercise states in subjective assessment of vascularity (P=0.131), fat pad motion (P=0.115), or percent change of the largest fat lobule (P=0.241). However, overall compressibility of the fat pad lobule was significantly diminished in the pre-exercise state in symptomatic knees compared to asymptomatic controls., Conclusions: This study demonstrated a statistically significant change in the largest vessel diameter from pre- to post-exercise states between symptomatic and asymptomatic knees, as well as abnormal pre-exercise fat lobule compressibility in symptomatic knees. These findings show promise that with further research, ultrasound could have clinical utility in diagnosing infrapatellar fat pad impingement., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Anterior cruciate ligament (ACL) reconstruction can effectively return athletes to the playing field, but they are still at risk of developing posttraumatic osteoarthritis (PTOA). No studies have used multivariable analysis to evaluate the predictors of radiographic PTOA in the lateral compartment of the knee at short-term follow-up after ACL reconstruction., Purpose: To determine the predictors of radiographic joint space narrowing in the lateral compartment 2 to 3 years after ACL reconstruction in a young, active cohort., Study Design: Cohort study; Level of evidence, 2., Methods: A nested cohort of 358 patients from the Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort who were aged ≤33 years, were injured playing a sport, and had never undergone surgery on the contralateral knee were followed up 2 years after ACL reconstruction with questionnaires and with weightbearing knee radiographs using the metatarsophalangeal (MTP) joint technique. The joint space width in the lateral compartment was measured using a semiautomatic computerized method, and multivariable predictive modeling was used to evaluate the relationship between meniscus treatment, cartilage injury, graft type, and joint space while adjusting for age, sex, body mass index, and Marx activity score., Results: The mean lateral joint space width was 0.11 mm narrower on the ACL-reconstructed knee compared with the contralateral healthy knee (7.69 mm vs 7.80 mm, respectively; P < .01). Statistically significant predictors of a narrower joint space width on the ACL-reconstructed knee included lateral meniscectomy ( P < .001) and a Marx activity score less than 16 points ( P < .001)., Conclusion: This study identifies lateral meniscectomy and a lower baseline Marx activity score to be predictors of radiographic joint space narrowing in the lateral compartment 2 to 3 years after ACL reconstruction in young, active patients without a prior knee injury.

Background: There are a multitude of treatments for low-grade lumbar spondylolisthesis. There are no clear guidelines for the optimal approach., Objective: To identify the surgical treatment patterns for spondylolisthesis among United States spine surgeons., Methods: 445 spine surgeons in the United States completed a survey of clinical/radiographic case scenarios on patients with lumbar spondylolisthesis with neurogenic claudication with (S+BP) or without (S-BP) associated mechanical back pain. Treatment options included decompression, laminectomy with posterolateral fusion, posterior lumbar interbody fusion, or none of the above. The primary outcome measure was the probability of 2 randomly chosen surgeons disagreeing on the treatment method., Results: There was 64% disagreement (36% agreement) among surgeons for treatment of spondylolisthesis with mechanical back pain (S+BP) and 71% disagreement (29% agreement) for spondylolisthesis without mechanical back pain (S-BP). For S+BP, disagreement was 52% for those practicing 5 to 10 years versus 70% among those practicing more than 20 years. Orthopedic surgeons had greater disagreement than did neurosurgeons (76% vs. 56%) for S+BP. Greater clinical equipoise was seen for S-BP than for S+BP regardless of surgeon characteristics. For spondylolisthesis without mechanical back pain, neurosurgeons were significantly more likely to select decompression-only than were orthopedic surgeons, who more commonly selected fusion., Conclusions: Clinical equipoise exists for the treatment of spondylolisthesis. Differences are greater when the patient presents without associated back pain. Surgeon case volume, practice duration, and specialty training influence operative decisions for a given pathologic condition. Recognizing this practice variation will hopefully lead to better evidence and practice guidelines for the optimal and most cost-effective treatment paradigms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to compare reader accuracy detecting lesions near hardware in a CT phantom model at different radiation exposures using an advanced metal artifact reduction (MAR) algorithm and standard filtered back projection (FBP) techniques and to determine if radiation exposure could be decreased using MAR without compromising lesion detectability., Materials and Methods: A CT phantom manufactured with spherical lesions of various sizes (10-20 mm) and attenuations (20-50 HU) embedded around cobalt-chromium spheres attached to titanium rods, simulating an arthroplasty, was scanned on a single CT scanner (FLASH, Siemens Healthcare) at 140 kVp and 0.6-mm collimation using clinical-dose (300 Quality Reference mAs [Siemens Healthcare]), low-dose (150 Quality Reference mAs), and high-dose (600 Quality Reference mAs) protocols. Images reconstructed with iterative MAR, advanced modeled iterative reconstruction (ADMIRE), and FBP with identical parameters were anonymized and independently reviewed by three radiologists. Accuracies for detecting lesions, measured as AUC, sensitivity, and specificity, were compared., Results: Accuracy using MAR was significantly higher than that using FBP at all exposures (p values ranged from < 0.001 to 0.021). Sensitivity was also higher for MAR than for FBP at all exposures. Specificity was very high for both reconstruction techniques at all exposures with no significant differences. Accuracy of low-dose MAR was higher than and not inferior to standard-dose and high-dose FBP. MAR was significantly more sensitive than FBP in detecting smaller lesions (p = 0.021) and lesions near high streak artifact (p < 0.001)., Conclusion: MAR improves reader accuracy to detect lesions near hardware and allows significant reductions in radiation exposure without compromising accuracy compared with FBP in a CT phantom model.

Rationale and Objectives: Quantitative imaging biomarkers (QIBs) are becoming increasingly adopted into clinical practice to monitor changes in patients' conditions. The repeatability coefficient (RC) is the clinical cut-point used to discern between changes in a biomarker's measurements due to measurement error and changes that exceed measurement error, thus indicating real change in the patient. Imaging biomarkers have characteristics that make them difficult for estimating the repeatability coefficient, including nonconstant error, non-Gaussian distributions, and measurement error that must be estimated from small studies., Methods: We conducted a Monte Carlo simulation study to investigate how well three statistical methods for estimating the repeatability coefficient perform under five settings common for QIBs., Results: When the measurement error is constant and replicates are normally distributed, all of the statistical methods perform well. When the measurement error is proportional to the true value, approaches that use the log transformation or coefficient of variation perform similarly. For other common settings, none of the methods for estimating the repeatability coefficient perform adequately., Conclusion: Many of the common approaches to estimating the repeatability coefficient perform well for only limited scenarios. The optimal approach depends strongly on the pattern of the within-subject variability; thus, a precision profile is critical in evaluating the technical performance of QIBs. Asymmetric bounds for detecting regression vs progression can be implemented and should be used when clinically appropriate., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose To determine the linearity, bias, and precision of hepatic proton density fat fraction (PDFF) measurements by using magnetic resonance (MR) imaging across different field strengths, imager manufacturers, and reconstruction methods. Materials and Methods This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search identified studies that evaluated the linearity and/or bias of hepatic PDFF measurements by using MR imaging (hereafter, MR imaging-PDFF) against PDFF measurements by using colocalized MR spectroscopy (hereafter, MR spectroscopy-PDFF) or the precision of MR imaging-PDFF. The quality of each study was evaluated by using the Quality Assessment of Studies of Diagnostic Accuracy 2 tool. De-identified original data sets from the selected studies were pooled. Linearity was evaluated by using linear regression between MR imaging-PDFF and MR spectroscopy-PDFF measurements. Bias, defined as the mean difference between MR imaging-PDFF and MR spectroscopy-PDFF measurements, was evaluated by using Bland-Altman analysis. Precision, defined as the agreement between repeated MR imaging-PDFF measurements, was evaluated by using a linear mixed-effects model, with field strength, imager manufacturer, reconstruction method, and region of interest as random effects. Results Twenty-three studies (1679 participants) were selected for linearity and bias analyses and 11 studies (425 participants) were selected for precision analyses. MR imaging-PDFF was linear with MR spectroscopy-PDFF (R 2 = 0.96). Regression slope (0.97; P < .001) and mean Bland-Altman bias (-0.13%; 95% limits of agreement: -3.95%, 3.40%) indicated minimal underestimation by using MR imaging-PDFF. MR imaging-PDFF was precise at the region-of-interest level, with repeatability and reproducibility coefficients of 2.99% and 4.12%, respectively. Field strength, imager manufacturer, and reconstruction method each had minimal effects on reproducibility. Conclusion MR imaging-PDFF has excellent linearity, bias, and precision across different field strengths, imager manufacturers, and reconstruction methods. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 2, 2017.

Purpose To (a) evaluate whether plaque tissue characteristics determined with conventional computed tomographic (CT) angiography could be quantitated at higher levels of accuracy by using image processing algorithms that take characteristics of the image formation process coupled with biologic insights on tissue distributions into account by comparing in vivo results and ex vivo histologic findings and (b) assess reader variability. Materials and Methods Thirty-one consecutive patients aged 43-85 years (average age, 64 years) known to have or suspected of having atherosclerosis who underwent CT angiography and were referred for endarterectomy were enrolled. Surgical specimens were evaluated with histopathologic examination to serve as standard of reference. Two readers used lumen boundary to determine scanner blur and then optimized component densities and subvoxel boundaries to best fit the observed image by using semiautomatic software. The accuracy of the resulting in vivo quantitation of calcification, lipid-rich necrotic core (LRNC), and matrix was assessed with statistical estimates of bias and linearity relative to ex vivo histologic findings. Reader variability was assessed with statistical estimates of repeatability and reproducibility. Results A total of 239 cross sections obtained with CT angiography and histologic examination were matched. Performance on held-out data showed low levels of bias and high Pearson correlation coefficients for calcification (-0.096 mm 2 and 0.973, respectively), LRNC (1.26 mm 2 and 0.856), and matrix (-2.44 mm 2 and 0.885). Intrareader variability was low (repeatability coefficient ranged from 1.50 mm 2 to 1.83 mm 2 among tissue characteristics), as was interreader variability (reproducibility coefficient ranged from 2.09 mm 2 to 4.43 mm 2 ). Conclusion There was high correlation and low bias between the in vivo software image analysis and ex vivo histopathologic quantitative measures of atherosclerotic plaque tissue characteristics, as well as low reader variability. Software algorithms can mitigate the blurring and partial volume effects of routine CT angiography acquisitions to produce accurate quantification to enhance current clinical practice. Clinical trial registration no. NCT02143102 © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on September 15, 2017.

Purpose: To compare diagnostic performance of a 5-min knee MRI protocol to that of a standard knee MRI., Materials and Methods: One hundred 3 T (100 patients, mean 38.8 years) and 50 1.5 T (46 patients, mean 46.4 years) MRIs, consisting of 5 fast, 2D multi-planar fast-spin-echo (FSE) sequences and five standard multiplanar FSE sequences, from two academic centers (1/2015-1/2016), were retrospectively reviewed by four musculoskeletal radiologists. Agreement between fast and standard (interprotocol agreement) and between standard (intraprotocol agreement) readings for meniscal, ligamentous, chondral, and bone pathology was compared for interchangeability. Frequency of major findings, sensitivity, and specificity was also tested for each protocol., Results: Interprotocol agreement using fast MRI was similar to intraprotocol agreement with standard MRI (83.0-99.5%), with no excess disagreement (≤ 1.2; 95% CI, -4.2 to 3.8%), across all structures. Frequency of major findings (1.1-22.4% across structures) on fast and standard MRI was not significantly different (p ≥ 0.215), except more ACL tears on fast MRI (p = 0.021) and more cartilage defects on standard MRI (p < 0.001). Sensitivities (59-100%) and specificities (73-99%) of fast and standard MRI were not significantly different for meniscal and ligament tears (95% CI for difference, -0.08-0.08). For cartilage defects, fast MRI was slightly less sensitive (95% CI for difference, -0.125 to -0.01) but slightly more specific (95% CI for difference, 0.01-0.5) than standard MRI., Conclusion: A fast 5-min MRI protocol is interchangeable with and has similar accuracy to a standard knee MRI for evaluating internal derangement of the knee.

Background: Venous sinus stenting for dural sinus stenoses is an emerging alternative to cerebrospinal fluid diversion in cases of medically refractory idiopathic intracranial hypertension. Juxta-stent 're-stenoses' have been reported and managed alternatively with ventricular shunting or stent revision. Identification of factors that might predispose patients to recurrent narrowing may help to select or exclude patients with idiopathic intracranial hypertension for venous sinus stenting., Methods: We retrospectively reviewed a prospectively maintained database spanning December 2011 to May 2015 of all patients with idiopathic intracranial hypertension who were screened for possible venous sinus stenting, including only patients who received a stent, noting symptomatic improvements, changes in opening lumbar puncture pressure, demographic characteristics, and any subsequent intervention after stent placement. Fisher's exact test and logistic regression were used to test each of seven potential predictors for retreatment., Results: There were eight revisions in 31 patients (25.8%). Among Caucasians, 8.0% required a revision compared with 100% of African-Americans (p<0.001). The c-index for race was 0.857. Body mass index (BMI) was also a significant predictor of revision (p=0.031): among class III obese patients the revision rate was 46.2% compared with 16.7% among class I and II obese patients and 0% among overweight to normal weight patients., Conclusions: BMI was a significant predictor of revision, suggesting that higher BMI may have a higher risk of revision. The small number of African-Americans in the study makes interpretation of the practical significance of the revision rate in these patients uncertain. None of the other studied factors was statistically significant., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Ischemic mitral regurgitation is associated with substantial risk of death. Although surgical mitral valve intervention (MVi) may improve symptoms, it has not been shown to improve survival. The aim of this study was to identify predictors of mortality in patients with ischemic mitral regurgitation and MVi., Methods and Results: We evaluated 117 consecutive patients (age, 65±10 years) with advanced ischemic cardiomyopathy who underwent cardiac magnetic resonance and subsequent MVi between January 1, 2002 and January 1, 2012. Cardiac magnetic resonance was used to assess left ventricular remodeling and myocardial scarring. The effective regurgitant orifice area was calculated from the proximal isovelocity surface area by echocardiography. There were 43 deaths (37%) during follow-up (median, 62 months). On multivariable analysis, age ≥70 years ( P =0.013), diabetes mellitus ( P =0.001), dyslipidemia ( P =0.012), papillary muscle scar ( P =0.010), incomplete revascularization ( P =0.001), and total scar %×effective regurgitant orifice area ≥0.20 cm 2 ( P =0.005) were each independently associated with all-cause mortality. Although patients with effective regurgitant orifice area <0.2 cm 2 at baseline demonstrated an increased hazard ratio of 3.3 for every 10% increase in scar, the hazard ratio increased to 9 for every 10% increase in scar in those with baseline effective regurgitant orifice area ≥0.20 cm 2 . Mortality also was significantly higher in patients with incomplete revascularization compared with those with vascularized viable myocardium (61% versus 28%; P <0.001)., Conclusions: Increased total scar burden and the presence of incomplete revascularization are powerful predictors of mortality in patients with advanced ischemic cardiomyopathy undergoing MVi. Viability assessment with cardiac magnetic resonance imaging can identify which patients with ischemic mitral regurgitation are at highest risk for mortality after surgical MVi., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: The two main objectives of the study include (1) Test the hypothesis that the lateral femoral condyle (LFC) in patients with primary OA and varus knees undergoing total knee arthroplasty (TKA) can be used as a model to better characterize varying histological features of human OA, (2) Correlate characteristic OA features using the established histopathological scoring systems (HHGS and OARSI) to understand potential histopathological patterns of OA initiation., Design: Two osteochondral specimens (4×4×8mm) were collected from fifty patient's LFC at the time of TKA (total 100 specimens), who presented preserved lateral knee compartment with joint space width>2mm. Three independent readers graded the sections on three different occasions using HHGS and OARSI systems. The correlation between individual parameters of the two scoring systems and their inter- and intra-reader variability, reliability and reproducibility were estimated., Results: All samples in this cohort showed abnormal histopathological features. Total histopathological scores of the LFC ranged from HHGS median=4.6 (range=0 to 11), and OARSI median=5.2 (range=0 to 19.5). The four individual sub-items of HHGS scoring system (structure, cells, safraninO staining, tidemark) were weakly correlated, with the correlation between structure and cellularity being the strongest (r=0.40). Both the scoring systems had similar repeatability and reproducibility coefficients of<21%., Conclusions: OA changes in the LFC are not confined to any one region, and maybe seen in different regions of cartilage, tidemark, subchondral bone, and/or the marrow space vascularity. These variations may point to the possibility of several potential patterns of initiation in OA., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose To perform a meta-analysis to generate an estimate of the repeatability coefficient (RC) for magnetic resonance (MR) elastography of the liver. Materials and Methods A systematic search of databases was performed for publications on MR elastography during the 10-year period between 2006 and 2015. The identified studies were screened independently and were verified reciprocally by all authors. Two reviewers independently determined the percentage RC and effective sample size from each article. A forest plot was constructed of the percentage RC estimates from the 12 studies. Bootstrap 95% confidence intervals (CIs) were constructed for the summary percentage RCs. Results Twelve studies comprising 274 patients met the eligibility criteria and were included for analysis. A flow diagram of studies included according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was prepared for the inclusion and exclusion criteria. All studies included in the meta-analysis fulfilled four or more of the seven categories of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. The estimated summary RC was 22% (95% CI: 16.1%, 28.2%). The three main sources for this heterogeneity were the trained versus untrained operator drawing contours to choose regions of interest, the time between two replicate examinations, and, finally, the field strength of the MR imaging unit. The RC estimates tended to be higher for studies that did not use a well-trained operator, those with 1.5-T field strength imaging units, and those with longer time intervals between examinations. Conclusion The meta-analysis results provide the basis for the following draft longitudinal Quantitative Imaging Biomarkers Alliance MR elastography claim: A measured change in hepatic stiffness of 22% or greater, at the same site and with use of the same equipment and acquisition sequence, indicates that a true change in stiffness has occurred with 95% confidence. © RSNA, 2017.

Rationale and Objectives: The purpose of this study was to characterize analytic performance of software-aided arterial vessel structure measurements across a range of scanner settings for computed tomography angiography where ground truth is known. We characterized performance for measurands that may be efficiently measured for clinical cases without use of software, as well as those that may be done manually but which is generally not done due to the effort level required unless software is employed., Materials and Methods: Four measurands (lumen area, stenosis, wall area, wall thickness) were evaluated using tissue-mimicking phantoms to estimate bias, heteroscedasticity, and limits of quantitation both pooled across scanner settings and individually for eight different settings. Reproducibility across scanner settings was also estimated., Results: Measurements of lumen area have a near constant bias of +1.3 mm for measurements ranging from 3 mm 2 to 40 mm 2 ; stenosis bias is +7% across a 30%-70% range; wall area bias is +14% across a 50-450 mm 2 range; and wall thickness bias is +1.2 mm across a 3-9 mm range. All measurements possess properties that make them suitable for measuring longitudinal change. Lumen area demonstrates the most sensitivity to scanner settings (bias from as low as +.1 mm to as high as +2.7 mm); wall thickness demonstrates negligible sensitivity., Conclusions: Variability across scanner settings for lumen measurands was generally higher than bias for a given setting. The converse was true for the wall measurands, where variability due to scanner settings was very low. Both bias and variability due to scanner settings of vessel structure were within clinically useful levels., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Rational and Objectives: This study aims to evaluate the diagnostic utility of breast imaging using transmission ultrasound. We present readers' accuracy in determining whether a breast lesion is a cyst versus a solid using transmission ultrasound as an adjunct to mammography., Materials and Methods: This retrospective multi-reader, multi-case receiver operating characteristic study included 37 lesions seen on mammography and transmission ultrasound. Cyst cases were confirmed as cysts using their appearance on handheld ultrasound. Solid cases were confirmed as solids with pathology results. Fourteen readers performed blinded, randomized reads with mammography + quantitative transmission scan images, assigning both a confidence score (0-100) and a binary classification of cyst or solid. A 95% percentile bootstrap confidence interval (CI) was computed for the readers' mean receiver operating characteristic area, sensitivity, and specificity., Results: Using the readers' binary classification of cyst or solid lesions, the mean sensitivity and specificity were 0.933 [95% CI: 0.837, 0.995] and 0.858 [95% CI: 0.701, 0.985], respectively. When the readers' confidence scores were used to distinguish a cyst versus solid, the mean receiver operating characteristic area was 0.920 [95% CI: 0.827, 0.985]., Conclusions: Transmission ultrasound can provide an accurate assessment of a cyst versus a solid lesion in the breast. Prospective clinical trials will further delineate the role of transmission ultrasound as an adjunct to mammography to increase specificity in breast evaluation., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Reversibility of left ventricular (LV) dysfunction in high-risk aortic stenosis patient and its impact on survival after transcatheter aortic valve replacement (TAVR) are unclear. We aimed to evaluate longitudinal changes of LV structure and function after TAVR and their impact on survival., Methods and Results: We studied 209 patients with aortic stenosis who underwent TAVR from May 2006 to December 2012. Echocardiograms were used to calculate LV end-diastolic volume index (LVEDVi), LV ejection fraction, LV mass index (LVMi), and global longitudinal strain before, immediately (<10 days), late (1-3 months), and yearly after TAVR. During a median follow-up of 1345 days, 118 patients died, with 26 dying within 1 year. Global longitudinal strain, LVEDVi, LV ejection fraction, and LVMi improved during follow-up. In patients who died during the first year, death was preceded by LVEDVi and LVMi increase. Multivariable longitudinal data analysis showed that aortic regurgitation at baseline, aortic regurgitation at 30 days, and initial LVEDVi were independent predictors of subsequent LVEDVi. In a joint analysis of longitudinal and survival data, baseline Society of Thoracic Surgeons score was predictive of survival, with no additive effect of longitudinal changes in LVEDVi, LVMi, global longitudinal strain, or LV ejection fraction. Presence of aortic regurgitation at 1 month after TAVR was the only predictor of 1-year survival., Conclusions: LV reverse remodeling was observed after TAVR, whereas lack of LVEDVi and LVMi improvement was observed in patients who died during the first year after TAVR. Post-TAVR, aortic regurgitation blocks reverse remodeling and is associated with poor 1-year survival after TAVR., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: The purpose of this study was to compare the diagnostic performance of a 5-minute shoulder MRI protocol consisting of multiplanar 2D fast spin-echo (FSE) sequences with parallel imaging to that of a standard shoulder MRI protocol., Materials and Methods: A retrospective review of 151 3-T MRI examinations of shoulders of 147 patients (mean age, 46.95 years) and 50 1.5-T MRI examinations of shoulders of 50 patients (mean age, 53.74 years) with four fast and five standard sequences from two academic centers between January 2014 and April 2015 was performed by three musculoskeletal radiologists. Interchangeability of fast and standard MRI was tested by comparing interprotocol (fast vs standard) interreader agreement with standard MRI interreader agreement. Interreader agreement was also compared using kappa statistics. The frequency of major findings was compared using an adjusted McNemar test. Sensitivity and specificity of MRI were measured for 51 patients who underwent surgery., Results: Interprotocol reader agreement was essentially equal to reader agreement on standard MRI (mean difference ≤ 1%; 95% CI, -3.8% to 3.9%; 61-96% across structures). Interprotocol kappa values (0.373-0.645) were similar to standard MRI kappa values (0.320-0.726). Frequencies of major findings on fast and standard MRI were similar (0.7-19.6% across structures; p ≥ 0.08). Sensitivities of fast MRI for tendon and labral tears (33-92%) were equivalent or higher than those of standard MRI with similar specificities (77-98%)., Conclusion: Fast 5-minute shoulder MRI with multiplanar 2D FSE sequences using parallel imaging is interchangeable, with similar interreader agreement and accuracy, with standard shoulder MRI for evaluating shoulder injuries.

Background: Accurate and consistent regional lymph node classification is an important element in the staging and multidisciplinary management of lung cancer. Regional lymph node definition sets-lymph node maps-have been created to standardize regional lymph node classification. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a lymph node map to supersede all preexisting lymph node maps. Our aim was to study if and how lung cancer specialists apply the IASLC lymph node map when classifying thoracic lymph nodes encountered on CT scans during lung cancer staging., Methods: From April 2013 through July 2013, invitations were distributed to all members of the Fleischner Society, Society of Thoracic Radiology, General Thoracic Surgical Club, and the American Association of Bronchology and Interventional Pulmonology to participate in an anonymous online image-based and text-based 20-question survey regarding lymph node classification for lung cancer staging on CT imaging., Results: Three hundred thirty-seven people responded (approximately 25% participation). Respondents consisted of self-reported thoracic radiologists (n = 158), thoracic surgeons (n = 102), and pulmonologists who perform endobronchial ultrasonography (n = 77). Half of the respondents (50%; 95% CI, 44%-55%) reported using the IASLC lymph node map in daily practice, with no significant differences between subspecialties. A disparity was observed between the IASLC definition sets and their interpretation and application on CT scans, in particular for lymph nodes near the thoracic inlet, anterior to the trachea, anterior to the tracheal bifurcation, near the ligamentum arteriosum, between the bronchus intermedius and esophagus, in the internal mammary space, and adjacent to the heart., Conclusions: Use of older lymph node maps and inconsistencies in interpretation and application of definitions in the IASLC lymph node map may potentially lead to misclassification of stage and suboptimal management of lung cancer in some patients., (Published by Elsevier Inc.)

Background: Optimal imaging triage for intervention for large vessel occlusions remains unclear. MR-based imaging provides ischemic core volumes at the cost of increased imaging time. CT Alberta Stroke Program Early CT Score (ASPECTS) estimates are faster, but may be less sensitive., Objective: To assesses the rate at which MRI changed management in comparison with CT imaging alone., Methods: Retrospective analysis of patients with acute ischemic stroke undergoing imaging triage for endovascular therapy was performed between 2008 and 2013. Univariate and multivariate analyses were performed. Multivariate logistic regression was used to evaluate the effect of time on disagreement in MRI and CT ASPECTS scores., Results: A total of 241 patients underwent both diffusion-weighted imaging (DWI) and CT. Six patients with DWI ASPECTS ≥6 and CT ASPECTS <6 were omitted, leaving 235 patients. For 47 patients, disagreement between the two modalities resulted in different treatment recommendations. The estimated probability of disagreement was 20.0% (95% CI 15.4% to 25.6%). In a multivariate logistic regression, CT ASPECTS >7 (p=0.004) and admission National Institutes of Health Stroke Scale (NIHSS) score <16 (p=0.008) were simultaneously significant predictors of agreement in ASPECTS. The time between modalities was a marginally significant predictor (p=0.080)., Conclusions: The study suggests that patients with NIHSS scores at admission of <16 and patients with CT ASPECTS >7 have a higher likelihood of agreement between CT and DWI based on an ASPECTS cut-off value of 6. Additional MRI for triage in patients with NIHSS at admission of >16, and ASPECTS of 6 or 7 may be more likely to change management. Unsurprisingly, patients with low CT ASPECTS had good correlation with MRI ASPECTS., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Biostatistics is an essential component in most original research studies in imaging. In this article we discuss five key statistical concepts for study design and analyses in modern imaging research: statistical hypothesis testing, particularly focusing on noninferiority studies; imaging outcomes especially when there is no reference standard; dealing with the multiplicity problem without spending all your study power; relevance of confidence intervals in reporting and interpreting study results; and finally tools for assessing quantitative imaging biomarkers. These concepts are presented first as examples of conversations between investigator and biostatistician, and then more detailed discussions of the statistical concepts follow. Three skeletal radiology examples are used to illustrate the concepts., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: Although positron emission tomography PET-MR imaging is emerging into clinical practice, many aspects of this imaging technique such as attenuation correction have yet to be validated for myocardial imaging. Thus, it is uncertain whether PET-MR FDG images provide clinical information which is comparable to PET-CT FDG images. The study goal was to systematically compare relative myocardial FDG concentrations obtained from cardiac PET-MR images to those derived from same day PET-CT images., Methods: Myocardial FDG images of 27 patients undergoing PET-CT imaging, followed by PET-MR imaging 42 ± 13 minutes later as part of a prospective oncology study were analyzed. Mean segmental standardized uptake measurements (SUVmean) were obtained in each of the 17 standard myocardial segments and normalized to the brightest segment., Results: Normalized segmental SUVmean values did not differ significantly between the PET-MR and PET-CT images (mean difference 0.002, P = .826). The specific segment was a marginally significant predictor of the differences (P = .057), with the largest difference in the anteroseptal basal segment., Conclusions: PET-MR, vis-à-vis PET-CT, does not significantly raise segmental uptake relative to the brightest segment, suggesting that PET-MR can be used similarly to PET-CT for applications where relative uptake is important.

Objective: The purpose of this study was to compare iterative metal artifact reduction (iMAR), a new single-energy metal artifact reduction technique, with filtered back projection (FBP) in terms of attenuation values, qualitative image quality, and streak artifacts near shoulder and hip arthroplasties and observer ability with these techniques to detect pathologic lesions near an arthroplasty in a phantom model., Materials and Methods: Preoperative and postoperative CT scans of 40 shoulder and 21 hip arthroplasties were reviewed. All postoperative scans were obtained using the same technique (140 kVp, 300 quality reference mAs, 128 × 0.6 mm detector collimation) on one of three CT scanners and reconstructed with FBP and iMAR. The attenuation differences in bones and soft tissues between preoperative and postoperative scans at the same location were compared; image quality and streak artifact for both reconstructions were qualitatively graded by two blinded readers. Observer ability and confidence to detect lesions near an arthroplasty in a phantom model were graded., Results: For both readers, iMAR had more accurate attenuation values (p < 0.001), qualitatively better image quality (p < 0.001), and less streak artifact (p < 0.001) in all locations near arthroplasties compared with FBP. Both readers detected more lesions (p ≤ 0.04) with higher confidence (p ≤ 0.01) with iMAR than with FBP in the phantom model., Conclusion: The iMAR technique provided more accurate attenuation values, better image quality, and less streak artifact near hip and shoulder arthroplasties than FBP; iMAR also increased observer ability and confidence to detect pathologic lesions near arthroplasties in a phantom model.

Purpose To assess image noise, contrast-to-noise ratio (CNR) and detectability of low-contrast, low-attenuation liver lesions in a semianthropomorphic phantom by using either a discrete circuit (DC) detector and filtered back projection (FBP) or an integrated circuit (IC) detector and iterative reconstruction (IR) with changes in radiation exposure and phantom size. Materials and Methods An anthropomorphic phantom without or with a 5-cm-thick fat-mimicking ring (widths, 30 and 40 cm) containing liver inserts with four spherical lesions was scanned with five exposure settings on each of two computed tomography scanners, one equipped with a DC detector and the other with an IC detector. Images from the DC and IC detector scanners were reconstructed with FBP and IR, respectively. Image noise and lesion CNR were measured. Four radiologists evaluated lesion presence on a five-point diagnostic confidence scale. Data analyses included receiver operating characteristic (ROC) curve analysis and noninferiority analysis. Results The combination of IC and IR significantly reduced image noise (P < .001) (with the greatest reduction in the 40-cm phantom and at lower exposures) and improved lesion CNR (P < .001). There was no significant difference in area under the ROC curve between detector-reconstruction combinations at fixed exposure for either phantom. Reader accuracy with IC-IR was noninferior at 50% (100 mAs [effective]) and 25% (300 mAs [effective]) exposure reduction for the 30- and 40-cm phantoms, respectively (adjusted P < .001 and .04 respectively). IC-IR improved readers' confidence in the presence of a lesion (P = .029) independent of phantom size or exposure level. Conclusion IC-IR improved objective image quality and lesion detection confidence but did not result in superior diagnostic accuracy when compared with DC-FBP. Moderate exposure reductions maintained comparable diagnostic accuracy for both detector-reconstruction combinations. Lesion detection in the 40-cm phantom was inferior at smaller exposure reduction than in the 30-cm phantom. (©) RSNA, 2016 Online supplemental material is available for this article.

Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all half-dose reconstructions than with full-dose FBP (mean proportion: 0.117 for half-dose FBP, 0.054 for half-dose SAFIRE 3, 0.054 for half-dose SAFIRE 4, and 0.017 for full-dose FBP; P < .001). Conclusion The diagnostic accuracy of half-dose CT enterography with FBP and SAFIRE is statistically noninferior to that of full-dose CT enterography for active inflammatory terminal ileal Crohn disease, despite an inferior subjective image quality. (©) RSNA, 2016 Online supplemental material is available for this article.

Objectives: To retrospectively investigate the role of Doppler sonography in the early detection of splenic steal syndrome., Methods: Fifty cases of splenic steal syndrome after orthotopic liver transplantation were identified. A control group was matched to the splenic steal syndrome group. Information was collected about the clinical presentation, liver enzyme levels, Doppler sonographic results, and follow-up after patients underwent splenic artery embolization., Results: A persistent hepatic arterial diastolic reversal waveform was observed in 25 patients with splenic steal syndrome versus 0 control patients. The mean hepatic arterial resistive index (RI) values ± SD were 0.95 ± 0.09 in patients with splenic steal syndrome and 0.80 ± 0.10 in control patients (P < .0001). One week after orthotopic liver transplantation, the area under the receiver operating characteristic curve for the RI was 0.884 (95% confidence interval, 0.793-0.975; P = .001) for splenic steal syndrome diagnosis. After splenic artery embolization, there was normalization of the reversal waveform, with an average RI of 0.77 ± 0.11 (P < .0001)., Conclusions: Dynamic changes in the hepatic arterial waveform and RI are keys to detecting splenic steal syndrome with Doppler sonography.

Background: Ischemic mitral regurgitation (IMR) is associated with poor outcomes. It is unknown what factors contribute to progression of IMR and how progressive IMR affects outcomes. We sought to determine imaging predictors of IMR progression and to determine if progressive IMR is an independent predictor of survival in patients with advanced ischemic cardiomyopathy., Methods and Results: Consecutive advanced ischemic cardiomyopathy patients who underwent cardiac magnetic resonance and echocardiograms at baseline with echocardiographic follow-up were studied. Cardiac magnetic resonance was used to assess left ventricular volumes, infarct size, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. Repeated measures mixed effects and Cox proportional hazards regression models were built to identify predictors of IMR progression and survival. We evaluated 336 patients (age, 62±11 years) over a median follow-up time of 54 months: 154 patients were subsequently revascularized, and 182 patients were medically treated. Ninety-eight patients (29%) demonstrated an increase in EROA values of ≥0.1 cm(2). There were 87 adverse events (death or transplant). On multivariable analysis, infarct size (P<0.001), progression in IMR (P=0.008), age (P=0.003), and baseline EROA (P=0.010) were independently associated with adverse events. Independent predictors of IMR progression were as follows: baseline EROA (P<0.001), left ventricular end-systolic volume index (P=0.014), and total scar (P=0.036)., Conclusions: IMR frequently increases in severity, and progression is independently associated with adverse left ventricular remodeling and infarct size, as assessed by cardiac magnetic resonance. Furthermore, IMR progression is a powerful independent predictor of adverse events, even after controlling for the severity of IMR at baseline., (© 2016 American Heart Association, Inc.)

Study Design: Electronic survey., Objective: To identify the surgical treatment patterns for low back pain (LBP), among U.S. spine surgeons. Specifically determine (1) differences in surgical treatment responses based on various demographic variables; (2) probability of disagreement based on surgeon subgroups., Summary of Background Data: Multiple surgical and nonsurgical treatments exist for LBP. Without strong evidence or clear guidelines for the indications and optimal treatments, there is substantial variability in surgical treatments used., Methods: A total of 445 U.S. spine surgeons completed a survey of clinical and radiographic case scenarios on patients with mechanical LBP, no leg pain, and concordant discograms. Surgical treatment options included no surgery, anterior lumbar interbody fusion (ALIF), posterolateral fusion with pedicle screws, transforaminal/posterior lumbar interbody fusion (TLIF/PLIF), etc. Statistical significance was set at 0.01 to account for multiple comparisons., Results: There was substantial clinical equipoise (∼75% disagreement) among surgeons on the approach to treat patients with LBP. Disagreement was highest in the southwest and lowest in the Midwest (82% vs. 69%, respectively); there was significantly lower disagreement among those in academic practices versus those in private/hybrid practices (56% vs.79%, respectively). Those in academic practices had approximately four times greater odds of choosing no surgery as compared to those in hybrid and private practices, who were more likely to choose ALIF or PLIF/TLIF. Those with fellowship training had approximately two times greater odds of selecting no surgery and four times greater odds of selecting ALIF as compared to those without fellowship training who were more likely to select TLIF/PLIF., Conclusion: Significant differences exist among U.S. spine surgeons in the treatment of LBP. These differences stem from geographical location of the practice, specialty, practice type, and fellowship training. Recognizing the substantial variability underlies the importance of additional studies aimed at identifying the proper indications and most cost-effective treatments for LBP., Level of Evidence: 3.

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.)

Objectives . This study presents correlations between cross-sectional anatomy of human female breasts and Quantitative Transmission (QT) Ultrasound, does discriminate classifier analysis to validate the speed of sound correlations, and does a visual grading analysis comparing QT Ultrasound with mammography. Materials and Methods . Human cadaver breasts were imaged using QT Ultrasound, sectioned, and photographed. Biopsies confirmed microanatomy and areas were correlated with QT Ultrasound images. Measurements were taken in live subjects from QT Ultrasound images and values of speed of sound for each identified anatomical structure were plotted. Finally, a visual grading analysis was performed on images to determine whether radiologists' confidence in identifying breast structures with mammography (XRM) is comparable to QT Ultrasound. Results . QT Ultrasound identified all major anatomical features of the breast, and speed of sound calculations showed specific values for different breast tissues. Using linear discriminant analysis overall accuracy is 91.4%. Using visual grading analysis readers scored the image quality on QT Ultrasound as better than on XRM in 69%-90% of breasts for specific tissues. Conclusions . QT Ultrasound provides accurate anatomic information and high tissue specificity using speed of sound information. Quantitative Transmission Ultrasound can distinguish different types of breast tissue with high resolution and accuracy., Competing Interests: This study was supported by QT Ultrasound Labs and by Grant 1RO1CA138536 from the National Cancer Institute. Nancy A. Obuchowski is a consultant for and the other authors are employees of QT Ultrasound Labs.

Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies.

Rationale and Objectives: Tumor volume change has potential as a biomarker for diagnosis, therapy planning, and treatment response. Precision was evaluated and compared among semiautomated lung tumor volume measurement algorithms from clinical thoracic computed tomography data sets. The results inform approaches and testing requirements for establishing conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Computed Tomography Volumetry Profile., Materials and Methods: Industry and academic groups participated in a challenge study. Intra-algorithm repeatability and inter-algorithm reproducibility were estimated. Relative magnitudes of various sources of variability were estimated using a linear mixed effects model. Segmentation boundaries were compared to provide a basis on which to optimize algorithm performance for developers., Results: Intra-algorithm repeatability ranged from 13% (best performing) to 100% (least performing), with most algorithms demonstrating improved repeatability as the tumor size increased. Inter-algorithm reproducibility was determined in three partitions and was found to be 58% for the four best performing groups, 70% for the set of groups meeting repeatability requirements, and 84% when all groups but the least performer were included. The best performing partition performed markedly better on tumors with equivalent diameters greater than 40 mm. Larger tumors benefitted by human editing but smaller tumors did not. One-fifth to one-half of the total variability came from sources independent of the algorithms. Segmentation boundaries differed substantially, not ony in overall volume but also in detail., Conclusions: Nine of the 12 participating algorithms pass precision requirements similar to what is indicated in the QIBA Profile, with the caveat that the present study was not designed to explicitly evaluate algorithm profile conformance. Change in tumor volume can be measured with confidence to within ±14% using any of these nine algorithms on tumor sizes greater than 10 mm. No partition of the algorithms was able to meet the QIBA requirements for interchangeability down to 10 mm, although the partition comprising best performing algorithms did meet this requirement for a tumor size of greater than approximately 40 mm., (Copyright © 2015 AUR. All rights reserved.)

Background: Cerebral angiography remains the gold standard for the detection of mycotic aneurysms, and it has been estimated that ruptured mycotic aneurysms result in 5% of the neurological complications of patients with infective endocarditis (IE)., Objective: To determine the diagnostic yield of cerebral angiography in the above patient population and to assess patient factors that might suggest greater or lesser utility., Methods: We retrospectively reviewed 168 patients who underwent cerebral angiography with a diagnosis of IE or infected left ventricular assist device at the Cleveland Clinic between January 2003 and March 2010 in accordance with institutional review board guidelines. Chart and imaging review was performed., Results: 15/168 patients (8.9%) had mycotic aneurysms; 93.3% (14/15) of the patients with mycotic aneurysms presented with CNS hemorrhage and 66.7% (10/15) had acute ischemic findings. Of the 15 patients with mycotic aneurysms on angiography, seven underwent CT angiography and six underwent MR angiography, which showed mycotic aneurysms in three (42.9%) and two cases (one of which was questionable; 33.3%), respectively., Conclusions: Patients with IE or similar sources of central bacterial emboli are prone to neurovascular complications. Approximately 9% of patients with IE at our institution who undergo cerebral angiography have mycotic aneurysms. Presentation with hemorrhage appears to be more predictive of aneurysm, as approximately 22% of patients with IE and hemorrhage were found to have an aneurysm compared with only 1% when hemorrhage was absent. Thus, patients with IE presenting with intracranial hemorrhage should undergo vascular imaging, preferably with cerebral angiography., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The goal of the study was to determine the effects of guideline implementation strategy using 2 commercial radiology clinical decision support (CDS) systems., Methods: The appropriateness and insurance dispositions of MRI and CT orders were evaluated using the Medicalis SmartReq and Nuance RadPort CDS systems during 2 different 3-month periods. Logistic regression was used to compare these outcomes between the 2 systems, after adjusting for patient-mix differences., Results: Approximately 2,000 consecutive outpatient MRI and CT orders were evaluated over 2 periods of 3 months each. Medicalis scored 60% of exams as "indeterminate" (insufficient information) or "not validated" (no guidelines). Excluding these cases, Nuance scored significantly more exams as appropriate than did Medicalis (80% versus 51%, P < .001) and predicted insurance outcome significantly more often (76% versus 58%, P < .001). Only when the Medicalis "indeterminate" and "not validated" categories were combined with the high- or moderate-utility categories did the 2 CDS systems have similar performance. Overall, 19% of examinations with low-utility ratings were reimbursed. Conversely, 0.8% of examinations with high- or moderate-utility ratings were denied reimbursement., Conclusions: The chief difference between the 2 CDS systems, and the strongest influence on outcomes, was how exams without relevant guidelines or with insufficient information were handled. Nuance augmented published guidelines with clinical best practice; Medicalis requested additional information utilizing pop-up windows. Thus, guideline implementation choices contributed to decision making and outcomes. User interface, specifically, the number of screens and completeness of indication choices, controlled CDS interactions and, coupled with guidance implementation, influenced willingness to use the CDS system., (Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort., Methods: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors., Results: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference., Conclusion: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study., (Copyright © 2015. Published by Elsevier Ltd.)

Quantitative imaging biomarkers are being used increasingly in medicine to diagnose and monitor patients' disease. The computer algorithms that measure quantitative imaging biomarkers have different technical performance characteristics. In this paper we illustrate the appropriate statistical methods for assessing and comparing the bias, precision, and agreement of computer algorithms. We use data from three studies of pulmonary nodules. The first study is a small phantom study used to illustrate metrics for assessing repeatability. The second study is a large phantom study allowing assessment of four algorithms' bias and reproducibility for measuring tumor volume and the change in tumor volume. The third study is a small clinical study of patients whose tumors were measured on two occasions. This study allows a direct assessment of six algorithms' performance for measuring tumor change. With these three examples we compare and contrast study designs and performance metrics, and we illustrate the advantages and limitations of various common statistical methods for quantitative imaging biomarker studies., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons. We first review and compare various study designs, including designs with the true value (e.g. phantoms, digital reference images, and zero-change studies), designs with a reference standard (e.g. studies testing equivalence with a reference standard), and designs without a reference standard (e.g. agreement studies and studies of algorithm precision). The statistical methods for comparing QIB algorithms are then presented for various study types using both aggregate and disaggregate approaches. We propose a series of steps for establishing the performance of a QIB algorithm, identify limitations in the current statistical literature, and suggest future directions for research., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)