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Accurate energy calibration is critical for the application of energy-resolved photon-counting detectors in spectral imaging. The aim of this study is to investigate the feasibility of energy response calibration and characterization of a photon-counting detector using x-ray fluorescence. A comprehensive Monte Carlo simulation study was performed using Geant4 Application for Tomographic Emission (GATE) to investigate the optimal technique for x-ray fluorescence calibration. Simulations were conducted using a 100 kVp tungsten-anode spectra with 2.7 mm Al filter for a single pixel cadmium telluride (CdTe) detector with 3 × 3 mm(2) in detection area. The angular dependence of x-ray fluorescence and scatter background was investigated by varying the detection angle from 20° to 170° with respect to the beam direction. The effects of the detector material, shape, and size on the recorded x-ray fluorescence were investigated. The fluorescent material size effect was considered with and without the container for the fluorescent material. In order to provide validation for the simulation result, the angular dependence of x-ray fluorescence from five fluorescent materials was experimentally measured using a spectrometer. Finally, eleven of the fluorescent materials were used for energy calibration of a CZT-based photon-counting detector. The optimal detection angle was determined to be approximately at 120° with respect to the beam direction, which showed the highest fluorescence to scatter ratio (FSR) with a weak dependence on the fluorescent material size. The feasibility of x-ray fluorescence for energy calibration of photon-counting detectors in the diagnostic x-ray energy range was verified by successfully calibrating the energy response of a CZT-based photon-counting detector. The results of this study can be used as a guideline to implement the x-ray fluorescence calibration method for photon-counting detectors in a typical imaging laboratory.

Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) applied to CAC scans can predict non-CHD events, including heart failure, atrial fibrillation, and stroke. We applied AI-enabled automated cardiac chambers volumetry and calcified plaque characterization to CAC scans (AI-CAC) of 5830 asymptomatic individuals (52.2% women, age 61.7 ± 10.2 years) in the multi-ethnic study of atherosclerosis during 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow-up for AI-CAC vs. Agatston score was (0.784 vs. 0.701), (0.771 vs. 0.709), (0.789 vs. 0.712) and (0.816 vs. 0.729) (p < 0.0001 for all), respectively. AI-CAC plaque characteristics, including number, location, density, plus number of vessels, significantly improved CHD prediction in the CAC 1-100 cohort vs. Agatston Score. AI-CAC significantly improved the Agatston score for predicting all CVD events., (© 2024. The Author(s).)

Background: We prospectively assessed the reproducibility of a novel low-dose single-volume dynamic computed tomography (CT) myocardial blood flow measurement technique., Methods: Thirty-four pairs of measurements were made under rest and stress conditions in 13 swine (54.3 ± 12.3 kg). One or two acquisition pairs were acquired in each animal with a 10-min delay between each pair. Contrast (370 mgI/mL; 0.5 mL/kg) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70 contrast/saline) were injected peripherally at 5 mL/s, followed by bolus tracking and acquisition of a single volume scan (100 kVp; 200 mA) with a 320-slice CT scanner. Bolus tracking and single volume scan data were used to derive perfusion in mL/min/g using a first-pass analysis model; the coronary perfusion territories of the left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) were automatically assigned using a previously validated minimum-cost path technique. The reproducibility of CT myocardial perfusion measurement within the LAD, LCx, RCA, and the whole myocardium was assessed via regression analysis. The average CT dose index (CTDI) of perfusion measurement was recorded., Results: The repeated first (P myo1 ) and second (P myo2 ) single-volume CT perfusion measurements were related by P myo2 = 1.01P myo1 - 0.03(ρ = 0.96; RMSE = 0.08 mL/min/g; RMSE = 0.07 mL/min/g) for the whole myocardium, and by P reg2 = 0.86P reg1 + 0.13(ρ = 0.87; RMSE = 0.31 mL/min/g; RMSE = 0.29 mL/min/g) for the LAD, LCx, and RCA perfusion territories. The average CTDI of the single-volume CT perfusion measurement was 10.5 mGy., Conclusion: The single-volume CT blood flow measurement technique provides reproducible low-dose myocardial perfusion measurement using only bolus tracking data and a single whole-heart volume scan., Relevance Statement: The single-volume CT blood flow measurement technique is a noninvasive tool that reproducibly measures myocardial perfusion and provides coronary CT angiograms, allowing for simultaneous anatomic-physiologic assessment of myocardial ischemia., Key Points: A low-dose single-volume dynamic CT myocardial blood flow measurement technique is reproducible. Motion misregistration artifacts are eliminated using a single-volume CT perfusion technique. This technique enables combined anatomic-physiologic assessment of coronary artery disease., (© 2024. The Author(s).)

Background: To evaluate the reproducibility of a vessel-specific minimum cost path (MCP) technique used for lobar segmentation on noncontrast computed tomography (CT)., Methods: Sixteen Yorkshire swine (49.9 ± 4.7 kg, mean ± standard deviation) underwent a total of 46 noncontrast helical CT scans from November 2020 to May 2022 using a 320-slice scanner. A semiautomatic algorithm was employed by three readers to segment the lung tissue and pulmonary arterial tree. The centerline of the arterial tree was extracted and partitioned into six subtrees for lobar assignment. The MCP technique was implemented to assign lobar territories by assigning lung tissue voxels to the nearest arterial tree segment. MCP-derived lobar mass and volume were then compared between two acquisitions, using linear regression, root mean square error (RMSE), and paired sample t-tests. An interobserver and intraobserver analysis of the lobar measurements was also performed., Results: The average whole lung mass and volume was 663.7 ± 103.7 g and 1,444.22 ± 309.1 mL, respectively. The lobar mass measurements from the initial (MLobe1) and subsequent (MLobe2) acquisitions were correlated by MLobe1 = 0.99 MLobe2 + 1.76 (r = 0.99, p = 0.120, RMSE = 7.99 g). The lobar volume measurements from the initial (VLobe1) and subsequent (VLobe2) acquisitions were correlated by VLobe1 = 0.98VLobe2 + 2.66 (r = 0.99, p = 0.160, RSME = 15.26 mL)., Conclusions: The lobar mass and volume measurements showed excellent reproducibility through a vessel-specific assignment technique. This technique may serve for automated lung lobar segmentation, facilitating clinical regional pulmonary analysis., Relevance Statement: Assessment of lobar mass or volume in the lung lobes using noncontrast CT may allow for efficient region-specific treatment strategies for diseases such as pulmonary embolism and chronic thromboembolic pulmonary hypertension., Key Points: • Lobar segmentation is essential for precise disease assessment and treatment planning. • Current methods for segmentation using fissure lines are problematic. • The minimum-cost-path technique here is proposed and a swine model showed excellent reproducibility for lobar mass measurements. • Interobserver agreement was excellent, with intraclass correlation coefficients greater than 0.90., (© 2024. The Author(s).)

Rationale and Objectives: To improve the image quality of CT pulmonary angiography (CTPA) using a patient-specific timing protocol., Material and Methods: A total of 24 swine (48.5 ± 14.3 kg) underwent continuous contrast-enhanced dynamic CT acquisition over 30 s to capture the pulmonary arterial input function (AIF). Multiple contrast injections were made under different cardiac outputs (1.4-5.1 L/min), resulting in a total of 154 AIF curves. The volume scans with maximal enhancement in these AIF curves were retrospectively selected as the reference standard (group A). Two prospective CTPA protocols with bolus-tracking were then simulated using these AIF curves: one used a fixed delay of 5 s between triggering and CTPA acquisition (group B), while the other used a specific delay based on one-half of the contrast injection duration (group C). The mean attenuation, signal-to-noise (SNR) and contrast-to-noise ratios (CNR) between the three groups were then compared using independent sample t -test. Subjective image quality scores were also compared using Wilcoxon-Mann-Whitney test., Results: The mean attenuation of pulmonary arteries for group A, B and C (expressed in [HU]) were 870.1 ± 242.5 HU, 761.1 ± 246.7 HU and 825.2 ± 236.8 HU, respectively. The differences in the mean SNR and CNR between Group A and Group C were not significant (SNR: 65.2 vs. 62.4, CNR: 59.6 vs. 56.4, both p > 0.05), while Group B was significantly lower than Group A ( p < 0.05)., Conclusion: The image quality of CT pulmonary angiography is significantly improved with a timing protocol determined using contrast injection delivery time, as compared with a standard timing protocol with a fixed delay between bolus triggering and image acquisition., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sabee Molloi reports financial support was provided by Canon America Medical Systems., (© 2023 The Author(s).)

Swine are commonly used for research on the respiratory system, but various anatomic features of the tracheobronchial tree of swine are poorly defined. The purpose of our study was to acquire normative measurements of the tracheobronchial tree of swine by using chest CT scans, thus laying a foundation for treating or studying airway disorders in this species. In our study, 33 male swine underwent thoracic CT scans; we measured anatomic features of the tracheobronchial tree, including the diameter, length, and angle of various airway structures. We further analyzed the relationships among selected principal parameters. Our data revealed several similarities and differences in anatomy between swine and humans. This information may be useful in future research.

Purpose: Agatston scoring does not detect all the calcium present in computed tomography scans of the heart. A technique that removes the need for thresholding and quantifies calcium mass more accurately and reproducibly is needed., Approach: Integrated intensity and volume fraction techniques were evaluated for accurate quantification of calcium mass. Integrated intensity calcium mass, volume fraction calcium mass, Agatston scoring, and spatially weighted calcium scoring were compared with known calcium mass in simulated and physical phantoms. The simulation was created to match a 320-slice CT scanner. Fat rings were added to the simulated phantoms, which resulted in small ( 30 × 20    cm 2 ), medium ( 35 × 25    cm 2 ), and large ( 40 × 30    cm 2 ) phantoms. Three calcification inserts of different diameters and hydroxyapatite densities were placed within the phantoms. All the calcium mass measurements were repeated across different beam energies, patient sizes, insert sizes, and densities. Physical phantom images from a previously reported study were then used to evaluate the accuracy and reproducibility of the techniques., Results: Both integrated intensity calcium mass and volume fraction calcium mass yielded lower root mean squared error (RMSE) and deviation (RMSD) values than Agatston scoring in all the measurements in the simulated phantoms. Specifically, integrated calcium mass (RMSE: 0.49 mg, RMSD: 0.49 mg) and volume fraction calcium mass (RMSE: 0.58 mg, RMSD: 0.57 mg) were more accurate for the low-density stationary calcium measurements than Agatston scoring (RMSE: 3.70 mg, RMSD: 2.30 mg). Similarly, integrated calcium mass (15.74%) and volume fraction calcium mass (20.37%) had fewer false-negative (CAC = 0) measurements than Agatston scoring (75.00%) and spatially weighted calcium scoring (26.85%), on the low-density stationary calcium measurements., Conclusion: The integrated calcium mass and volume fraction calcium mass techniques can potentially improve risk stratification for patients undergoing calcium scoring and further improve risk assessment compared with Agatston scoring., (© 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: Computed tomography pulmonary angiography (CTPA) is the primary modality for the detection and diagnosis of pulmonary embolism (PE) while the stratification of PE severity remains challenging using angiography. Hence, an automated minimum-cost path (MCP) technique was validated to quantify the subtended lung tissue distal to emboli using CTPA., Methods: A Swan-Ganz catheter was placed in the pulmonary artery of seven swine (body weight: 42.6±9.6 kg) to produce different PE severities. A total of 33 embolic conditions were generated, where the PE location was adjusted under fluoroscopic guidance. Each PE was induced by balloon inflation followed by computed tomography (CT) pulmonary angiography and dynamic CT perfusion scans using a 320-slice CT scanner. Following image acquisition, the CTPA and the MCP technique were used to automatically assign the ischemic perfusion territory distal to the balloon. Dynamic CT perfusion was used as the reference standard (REF) where the low perfusion territory was designated as the ischemic territory. The accuracy of the MCP technique was then evaluated by quantitatively comparing the MCP-derived distal territories to the perfusion-derived reference distal territories by mass correspondence using linear regression, Bland-Altman analysis, and paired sample t -test. The spatial correspondence was also assessed., Results: The MCP-derived distal territory masses ( Mass MCP , g) and the reference standard ischemic territory masses ( Mass REF , g) were related by Mass MCP =1.02 Mass REF - 0.62 g (r=0.99, paired t -test P=0.51). The mean Dice similarity coefficient was 0.84±0.08., Conclusions: The MCP technique enables accurate assessment of lung tissue at risk distal to a PE using CTPA. This technique can potentially be used to quantify the fraction of lung tissue at risk distal to PE to further improve the risk stratification of PE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-791/coif). S Molloi has previously received grants from Canon America Medical Systems. The other authors have no conflicts of interest to declare, (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aims: The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women., Methods and Results: We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing. Among 4908 women, 354 incident cases of AF (7%) were ascertained after a mean (standard deviation) of 7 (2) years of follow-up. In Cox regression adjusting for a propensity score for BAC, BAC presence vs. absence was not significantly associated with AF [hazard ratio (HR) = 1.12; 95% confidence interval (CI), 0.89-1.42; P = 0.34]. However, a significant (a priori hypothesized) age by BAC interaction was found ( P = 0.02) such that BAC presence was not associated with incident AF in women aged 60-69 years (HR = 0.83; 95% CI, 0.63-1.15; P = 0.26) but was significantly associated with incident AF in women aged 70-79 years (HR = 1.75; 95% CI, 1.21-2.53; P = 0.003). No evidence of dose-response relationship between BAC gradation and AF was noted in the entire cohort or in age groups separately., Conclusion: Our results demonstrate, for the first time, an independent association between BAC and AF in women over age 70 years., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown., Methods: Cohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Pre-specified endpoints were incident coronary heart disease (CHD), ischemic stroke, heart failure and its subtypes and all CVD., Results: After 7.4 (SD = 1.7) years of follow-up, 51 CHD, 30 ischemic stroke and 46 heart failure events were ascertained. At a limit of detection of 1.6 ng/L, 98.3 of the cohort had measurable hsTnI concentration. HsTnI in the 4-10 ng/L range were independently associated of CHD (adjusted hazard ratio[aHR] = 2.78; 95% CI, 1.48-5.22; p = 0.002) and all CVD (aHR = 2.06; 95% CI, 1.37-3.09; p = 0.0005) and hsTnI over 10 ng/L was independently associated with CHD (aHR = 4.75; 95% CI, 1.83-12.3; p = 0.001), ischemic stroke (aHR = 3.81; 95% CI, 1.22-11.9; p = 0.02), heart failure (aHR = 3.29; 95% CI, 1.33-8.13; p = 0.01) and all CVD (aHR = 4.78; 95% CI, 2.66-8.59; p < 0.0001). No significant association was found between hsTnI and BAC. Adding hsTnI to a model containing the Pooled Cohorts Equation resulted in significant and clinical important improved calibration, discrimination (Δ C index  = 6.5; p = 0.02) and reclassification (bias-corrected clinical NRI = 0.18; 95% CI, -0.13-0.49 after adding hsTnI categories)., Conclusions: Our results support the consideration of hsTnI as a risk enhancing factor for CVD in asymptomatic women that could drive preventive or therapeutic decisions., Competing Interests: C.I. is a consultant for Abbott Diagnostics. 10.13039/100014386Abbott Diagnostics performed the ARCHITECT assays for hs-cTn I and BNP and provided financial support to the MINERVA Biomarkers Study., (© 2022 The Authors.)

The aim of this study was to validate a motion-immune (MI) solution to dynamic CT myocardial perfusion measurement, in the presence of motion without image registration. The MI perfusion technique was retrospectively validated in six swine (37.3 ± 7.5 kg) with a motion-susceptible (MS) perfusion technique performed for comparison. In each swine, varying severities of stenoses were generated in the left anterior descending (LAD) coronary artery using a balloon under intracoronary adenosine stress, followed by contrast-enhanced imaging with 20 consecutive volume scans per stenosis. Two volume scans were then systematically selected from each acquisition for both MI and MS perfusion measurement, where the resulting LAD and left circumflex (LCx) measurements were compared to reference microsphere perfusion measurements using regression and diagnostic performance analysis. The MI (P MI ) and microsphere (P MICRO ) perfusion measurements were related through regression by P MI  = 0.98 P MICRO  + 0.03 (r = 0.97), while the MS (P MS ) and microsphere (P MICRO ) perfusion measurements were related by P MS  = 0.62 P MICRO  + 0.15 (r = 0.89). The accuracy of the MI and MS techniques in detecting functionally significant stenosis was 93% and 84%, respectively. The motion-immune (MI) perfusion technique provides accurate myocardial perfusion measurement in the presence of motion without image registration., (© 2022. The Author(s).)

The purpose of this study is to develop and validate an optimal timing protocol for a low-radiation-dose CT pulmonary perfusion technique using only two volume scans. A total of 24 swine (48.5 ± 14.3 kg) underwent contrast-enhanced dynamic CT. Multiple contrast injections were made under different pulmonary perfusion conditions, resulting in a total of 141 complete pulmonary arterial input functions (AIFs). Using all the AIF curves, an optimal contrast timing protocol was developed for a first-pass, two-volume dynamic CT perfusion technique (one at the base and the other at the peak of AIF curve). A subset of swine was used to validate the prospective two-volume pulmonary perfusion technique. The prospective two-volume perfusion measurements were quantitatively compared to the previously validated retrospective perfusion measurements with t-test, linear regression, and Bland-Altman analysis. As a result, the pulmonary artery time-to-peak ([Formula: see text]) was related to one-half of the contrast injection duration ([Formula: see text]) by [Formula: see text] (r = 0.95). The prospective two-volume perfusion measurements (P PRO ) were related to the retrospective measurements (P RETRO ) by P PRO  = 0.87P RETRO  + 0.56 (r = 0.88). The CT dose index and size-specific dose estimate of the two-volume CT technique were estimated to be 28.4 and 47.0 mGy, respectively. The optimal timing protocol can enable an accurate, low-radiation-dose two-volume dynamic CT perfusion technique., (© 2022. The Author(s).)

Background: Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD., Methods: A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD., Results: Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P =0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P =0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P =0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P =0.04) after adding BAC status., Conclusions: Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.

Purpose: To evaluate the accuracy of a low-dose first-pass analysis (FPA) CT pulmonary perfusion technique in comparison to fluorescent microsphere measurement as the reference standard., Method: The first-pass analysis CT perfusion technique was validated in six swine (41.7 ± 10.2 kg) for a total of 39 successful perfusion measurements. Different perfusion conditions were generated in each animal using serial balloon occlusions in the pulmonary artery. For each occlusion, over 20 contrast-enhanced CT images were acquired within one breath (320 x 0.5mm collimation, 100kVp, 200mA or 400mA, 350ms gantry rotation time). All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for the FPA measurement. Both MSM and FPA perfusion measurements were then compared to the reference fluorescent microsphere measurements., Results: The mean lung perfusion of MSM, FPA, and microsphere measurements were 6.21 ± 3.08 (p = 0.008), 6.59 ± 3.41 (p = 0.44) and 6.68 ± 3.89 ml/min/g, respectively. The MSM (PMSM) and FPA (PFPA) perfusion measurements were related to the corresponding reference microsphere measurement (PMIC) by PMSM = 0.51PMIC + 2.78 (r = 0.64) and PFPA = 0.79PMIC + 1.32 (r = 0.90). The root-mean-square-error for the MSM and FPA techniques were 3.09 and 1.72 ml/min/g, respectively. The root-mean-square-deviation for the MSM and FPA techniques were 2.38 and 1.50 ml/min/g, respectively. The CT dose index for MSM and FPA techniques were 138.7 and 8.4mGy, respectively., Conclusions: The first-pass analysis technique can accurately measure regional pulmonary perfusion and has the potential to reduce the radiation dose associated with dynamic CT perfusion for assessment of pulmonary disease., Competing Interests: The authors have declared that no competing interests exist.

Context: The association between bone mineral density (BMD) and breast arterial calcification (BAC) remains poorly understood and controversial., Objective: The objective of this article is to examine the association between BMD and BAC in a large cohort of postmenopausal women undergoing routine mammography., Design: A cross-sectional analysis of baseline data from a multiethnic cohort was performed., Setting: The setting for this analysis is an integrated health care delivery system in Northern California in the United States., Patients: A total of 1273 women age 60 to 79 years (mean age, 67 years) were recruited within 12 months of screening mammography., Main Outcome Measure: A BAC score (mg) was obtained from digital mammograms using a novel densitometry method. BAC presence was defined as a BAC score greater than 0 mg, and severe BAC as a BAC score greater than 20 mg., Results: Overall, 53% of women had osteopenia and 21% had osteoporosis. The prevalence of BAC greater than 0 mg was 29%, 30%, and 29% among women with normal BMD, osteopenia, and osteoporosis, respectively ( P  = 0.98). The prevalence of BAC greater than 20 mg was 5%, 3%, and 5% among women with normal BMD, osteopenia and osteoporosis, respectively ( P  = .65). The odds ratios (ORs) of BAC greater than 0 mg vs BAC = 0 mg after multivariable adjustment were 1.09 (95% CI, 0.81-1.48; P  = .54) for osteopenia and 0.99 (95% CI, 0.69-1.48; P  = .98) for osteoporosis. The adjusted ORs for BAC greater than 20 mg vs BAC 20 mg or less were 1.03 (95% CI, 0.52-2.01; P  = .93) for osteopenia and 1.89 (95 CI, 0.81-4.47; P  = .14) for osteoporosis., Conclusion: Our findings do not support an association of either osteopenia or osteoporosis with BAC presence or severity among postmenopausal women., (© Endocrine Society 2019.)

Rationale and Objectives: The accuracy of coronary computed tomography (CT) angiography depends upon the degree of coronary enhancement as compared to the background noise. Unfortunately, coronary contrast-to-noise ratio (CNR) optimization is difficult on a patient-specific basis. Hence, the objective of this study was to validate a new combined diluted test bolus and CT angiography protocol for improved coronary enhancement and CNR., Materials and Methods: The combined diluted test bolus and CT angiography protocol was validated in six swine (28.9 ± 2.7 kg). Specifically, the aortic and coronary enhancement and CNR of a standard CT angiography protocol, and a new combined diluted test bolus and CT angiography protocol were compared to a reference retrospective CT angiography protocol. Comparisons for all data were made using box plots, t tests, regression, Bland-Altman, root-mean-square error and deviation, as well as Lin's concordance correlation., Results: The combined diluted test bolus and CT angiography protocol was found to improve aortic and coronary enhancement by 26% and 13%, respectively, as compared to the standard CT angiography protocol. More importantly, the combined protocol was found to improve aortic and coronary CNR by 29% and 20%, respectively, as compared to the standard protocol., Conclusion: A new combined diluted test bolus and CT angiography protocol was shown to improve coronary enhancement and CNR as compared to an existing standard CT angiography protocol., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial perfusion measurement with a low-dose first-pass analysis (FPA) dynamic computed tomography (CT) perfusion technique depends upon acquisition of two whole-heart volume scans at the base and peak of the aortic enhancement. Hence, the objective of this study was to validate an optimal timing protocol for volume scan acquisition at the base and peak of the aortic enhancement., Methods: Contrast-enhanced CT of 28 Yorkshire swine (weight, 55 ± 24 kg, mean ± standard deviation) was performed under rest and stress conditions over 20-30 s to capture the aortic enhancement curves. From these curves, an optimal timing protocol was simulated, where one volume scan was acquired at the base of the aortic enhancement while a second volume scan was acquired at the peak of the aortic enhancement. Low-dose FPA perfusion measurements (P FPA ) were then derived and quantitatively compared to the previously validated retrospective FPA perfusion measurements as a reference standard (P REF ). The 32-cm diameter volume CT dose index, [Formula: see text] and size-specific dose estimate (SSDE) of the low-dose FPA perfusion protocol were also determined., Results: P FPA were related to the reference standard by P FPA  = 0.95 · P REF  + 0.07 (r = 0.94, root-mean-square error = 0.27 mL/min/g, root-mean-square deviation = 0.04 mL/min/g). The [Formula: see text] and SSDE of the low-dose FPA perfusion protocol were 9.2 mGy and 14.6 mGy, respectively., Conclusions: An optimal timing protocol for volume scan acquisition at the base and peak of the aortic enhancement was retrospectively validated and has the potential to be used to implement an accurate, low-dose, FPA perfusion technique.

We developed three-dimensionally (3D) printed patient-specific coronary phantoms that are capable of sustaining physiological flow and pressure conditions. We assessed the accuracy of these phantoms from coronary CT acquisition, benchtop experimentation, and CT-FFR software. Five patients with coronary artery disease underwent 320-detector row coronary CT angiography (CCTA) (Aquilion ONE, Canon Medical Systems) and a catheter lab procedure to measure fractional flow reserve (FFR). The aortic root and three main coronary arteries were segmented (Vitrea, Vital Images) and 3D printed (Eden 260V, Stratasys). Phantoms were connected into a pulsatile flow loop, which replicated physiological flow and pressure gradients. Contrast was introduced and the phantoms were scanned using the same CT scanner model and CCTA protocol as used for the patients. Image data from the phantoms were input to a CT-FFR research software (Canon Medical Systems) and compared to those derived from the clinical data, along with comparisons between image measurements and benchtop FFR results. Phantom diameter measurements were within 1 mm on average compared to patient measurements. Patient and phantom CT-FFR results had an absolute mean difference of 4.34% and Pearson correlation of 0.95. We have demonstrated the capabilities of 3D printed patient-specific phantoms in a diagnostic software.

Background: Breast arterial calcification (BAC) may be a predictor of cardiovascular events and is highly prevalent in persons with end-stage kidney disease. However, few studies to date have examined the association between mild-to-moderate kidney function and proteinuria with BAC., Methods: We prospectively enrolled women with no prior cardiovascular disease aged 60 to 79 years undergoing mammography screening at Kaiser Permanente Northern California between 10/24/2012 and 2/13/2015. Urine albumin-to-creatinine ratio (uACR), along with specific laboratory, demographic, and medical data, were measured at the baseline visit. Baseline estimated glomerular filtration rate (eGFR), medication history, and other comorbidities were identified from self-report and/or electronic medical records. BAC presence and gradation (mass) was measured by digital quantification of full-field mammograms., Results: Among 3,507 participants, 24.5% were aged ≥70 years, 63.5% were white, 7.5% had eGFR <60 ml/min/1.73m2, with 85.7% having uACR ≥30 mg/g and 3.3% having uACR ≥300 mg/g. The prevalence of any measured BAC (>0 mg) was 27.9%. Neither uACR ≥30 mg/g nor uACR ≥300 were significantly associated with BAC in crude or multivariable analyses. Reduced eGFR was associated with BAC in univariate analyses (odds ratio 1.53, 95% CI: 1.18-2.00), but the association was no longer significant after adjustment for potential confounders. Results were similar in various sensitivity analyses that used different BAC thresholds or analytic approaches., Conclusions: Among women without cardiovascular disease undergoing mammography screening, reduced eGFR and albuminuria were not significantly associated with BAC., Competing Interests: Seven of the authors are affiliated with Kaiser Permanente Northern California [RVP, CI, CL, TLH, TCT, GS, ASG] which served as the primary source for participants and collected data. This does not alter our adherence to PLOS ONE policies on sharing data and materials. We have no other competing interests to declare.

Coronary artery disease is a major cause of death in women. Breast arterial calcifications (BACs), detected inmammograms, can be useful riskmarkers associated with the disease. We investigate the feasibility of automated and accurate detection ofBACsinmammograms for risk assessment of coronary artery disease. We develop a 12-layer convolutional neural network to discriminate BAC from non-BAC and apply a pixelwise, patch-based procedure for BAC detection. To assess the performance of the system, we conduct a reader study to provide ground-truth information using the consensus of human expert radiologists. We evaluate the performance using a set of 840 full-field digital mammograms from 210 cases, using both free-responsereceiveroperatingcharacteristic (FROC) analysis and calcium mass quantification analysis. The FROC analysis shows that the deep learning approach achieves a level of detection similar to the human experts. The calcium mass quantification analysis shows that the inferred calcium mass is close to the ground truth, with a linear regression between them yielding a coefficient of determination of 96.24%. Taken together, these results suggest that deep learning can be used effectively to develop an automated system for BAC detection inmammograms to help identify and assess patients with cardiovascular risks.

Background: Computed tomographic (CT) angiography is an important tool for the evaluation of coronary artery disease but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed., Methods and Results: A total of 20 contrast-enhanced CT volume scans were acquired in 5 swine (40±10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending coronary artery, and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only 2 volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by P FPA =1.01 FFR-0.03 (R 2 =0.85) and P MSM =1.03 FFR-0.03 (R 2 =0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively., Conclusions: A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of coronary artery disease at a relatively low radiation dose., (© 2016 American Heart Association, Inc.)

This work develops a material reconstruction method for spectral CT, namely Total Image Constrained Material Reconstruction (TICMR), to maximize the utility of projection data in terms of both spectral information and high signal-to-noise ratio (SNR). This is motivated by the following fact: when viewed as a spectrally-integrated measurement, the projection data can be used to reconstruct a total image without spectral information, which however has a relatively high SNR; when viewed as a spectrally-resolved measurement, the projection data can be utilized to reconstruct the material composition, which however has a relatively low SNR. The material reconstruction synergizes material decomposition and image reconstruction, i.e., the direct reconstruction of material compositions instead of a two-step procedure that first reconstructs images and then decomposes images. For material reconstruction with high SNR, we propose TICMR with nonlocal total variation (NLTV) regularization. That is, first we reconstruct a total image using spectrally-integrated measurement without spectral binning, and build the NLTV weights from this image that characterize nonlocal image features; then the NLTV weights are incorporated into a NLTV-based iterative material reconstruction scheme using spectrally-binned projection data, so that these weights serve as a high-SNR reference to regularize material reconstruction. Note that the nonlocal property of NLTV is essential for material reconstruction, since material compositions may have significant local intensity variations although their structural information is often similar. In terms of solution algorithm, TICMR is formulated as an iterative reconstruction method with the NLTV regularization, in which the nonlocal divergence is utilized based on the adjoint relationship. The alternating direction method of multipliers is developed to solve this sparsity optimization problem. The proposed TICMR method was validated using both simulated and experimental data. In comparison with FBP and total-variation-based iterative method, TICMR had improved image quality, e.g., contrast-to-noise ratio and spatial resolution.

Rationale and Objectives: The purpose of this study was to compare the precision of mammographic breast density measurement using radiologist reader assessment, histogram threshold segmentation, fuzzy C-mean segmentation, and spectral material decomposition., Materials and Methods: Spectral mammography images from a total of 92 consecutive asymptomatic women (aged 50-69 years) who presented for annual screening mammography were retrospectively analyzed for this study. Breast density was estimated using 10 radiologist reader assessment, standard histogram thresholding, fuzzy C-mean algorithm, and spectral material decomposition. The breast density correlation between left and right breasts was used to assess the precision of these techniques to measure breast composition relative to dual-energy material decomposition., Results: In comparison to the other techniques, the results of breast density measurements using dual-energy material decomposition showed the highest correlation. The relative standard error of estimate for breast density measurements from left and right breasts using radiologist reader assessment, standard histogram thresholding, fuzzy C-mean algorithm, and dual-energy material decomposition was calculated to be 1.95, 2.87, 2.07, and 1.00, respectively., Conclusions: The results indicate that the precision of dual-energy material decomposition was approximately factor of two higher than the other techniques with regard to better correlation of breast density measurements from right and left breasts., (Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.)

Background: Diastolic fractional flow reserve (dFFR) has been shown to be highly sensitive for detection of inducible myocardial ischemia. However, its reliance on measurement of left-ventricular pressure for zero-flow pressure correction, as well as manual extraction of the diastolic interval, has been its major limitation. Given previous reports of minimal zero-flow pressure at end-diastole, we compared instantaneous ECG-gated end-diastolic FFR with conventional full-cardiac cycle FFR and other diastolic indices in the porcine model., Methods and Results: Measurements of FFR in the left anterior descending and left circumflex arteries were performed in an open-chest swine model with an external occluder device on the coronary artery used to produce varying degrees of epicardial stenosis. An ultrasound flow-probe that was placed proximal to the occluder measured absolute blood flow in ml/min, and it was used as a gold standard for FFR measurement. A total of 17 measurements at maximal hyperemia were acquired in 5 animals. Correlation coefficient between conventional mean hyperemic FFR with pressure-wire and directly measured FFR with flow-probe was 0.876 (standard error estimate=0.069; P<0.0001). The hyperemic end-diastolic FFR with pressure-wire correlated better with FFR measured directly with flow-probe (r=0.941, standard error estimate=0.050; P<0.0001)., Conclusions: Instantaneous hyperemic ECG-gated FFR acquired at end-diastole, as compared with conventional full-cardiac cycle FFR, has an improved correlation with FFR measured directly with ultrasound flow-probe.

Coronary flow reserve (CFR) and fractional flow reserve (FFR) are important physiological indexes for coronary disease. The purpose of this study was to validate the CFR and FFR measurement techniques using only angiographic image data. Fifteen swine were instrumented with an ultrasound flow probe on the left anterior descending artery (LAD). Microspheres were gradually injected into the LAD to create microvascular disruption. An occluder was used to produce stenosis. Contrast material injections were made into the left coronary artery during image acquisition. Volumetric blood flow from the flow probe (Q(q)) was continuously recorded. Angiography-based blood flow (Q(a)) was calculated by using a time-density curve based on the first-pass analysis technique. Flow probe-based CFR (CFR(q)) and angiography-based CFR (CFR(a)) were calculated as the ratio of hyperemic to baseline flow using Q(q) and Q(a), respectively. Relative angiographic FFR (relative FFR(a)) was calculated as the ratio of the normalized Q(a) in LAD to the left circumflex artery (LC(X)) during hyperemia. Flow probe-based FFR (FFR(q)) was measured from the ratio of hyperemic flow with and without disease. CFR(a) showed a strong correlation with the gold standard CFR(q) (CFR(a) = 0.91 CFR(q) + 0.30; r = 0.90; P < 0.0001). Relative FFR(a) correlated linearly with FFR(q) (relative FFR(a) = 0.86 FFR(q) + 0.05; r = 0.90; P < 0.0001). The quantification of CFR and relative FFR(a) using angiographic image data was validated in a swine model. This angiographic technique can potentially be used for coronary physiological assessment during routine cardiac catheterization.

Coronary microvascular dysfunction has important prognostic implications. Several hemodynamic indexes, such as coronary flow reserve (CFR), microvascular resistance, and zero-flow pressure (P(zf)), were used to establish the most reliable index to assess coronary microcirculation. Fifteen swine were instrumented with a flow probe, and a pressure wire was advanced into the distal left anterior descending artery. Adenosine was used to produce maximum hyperemia. Microspheres were used to create microvascular dysfunction. An occluder was used to produce stenosis. Blood flow from the probe (Q(p)), aortic pressure, distal coronary pressure, and right atrium pressure were recorded. Angiographic flow (Q(a)) was calculated using a time-density curve. Flow probe-based CFR and angiographic CFR were calculated using Q(p) and Q(a), respectively. Flow probe-based (NMR(qh)) and angiographic normalized microvascular resistance (NMR(ah)) were determined using Q(p) and Q(a), respectively, during hyperemia. P(zf) was calculated using Q(p) and distal coronary pressure. Two series of receiver operating characteristic curves were generated: normal epicardial artery model (N model) and stenosis model (S model). The areas under the receiver operating characteristic curves for flow probe-based CFR, angiographic CFR, NMR(qh), NMR(ah), and P(zf) were 0.855, 0.836, 0.976, 0.956, and 0.855 in N model and 0.737, 0.700, 0.935, 0.889, and 0.698 in S model. Both NMR(qh) and NMR(ah) were significantly more reliable than CFR and P(zf) in detecting the microvascular deterioration. Compared with CFR and P(zf), NMR provided a more accurate assessment of microcirculation. This improved accuracy was more prevalent when stenosis existed. Moreover, NMR(ah) is potentially a less invasive method for assessing coronary microcirculation.

Coronary flow reserve (CFR) is an important index of coronary microcirculatory function. The objective of this study was to validate the reproducibility and accuracy of intravascular conductance catheter-based method for measurements of baseline and hyperemic coronary flow velocity (and hence CFR). The absolute coronary blood velocity was determined by measuring the time of transit of a saline injection between two pairs of electrodes (known distance) on a conductance catheter during a routine saline injection without the need for reference flow. In vitro validation was made in the velocity range of 5 to 70 cm/s in reference to the volume collection method. In 10 swine, velocity measurements were compared with those from a flow probe in coronary arteries at different CFR attained by microsphere embolization. In vitro, the mean difference between the proposed method and volume collection was 0.7 ± 1.34 cm/s for steady flow and -0.77 ± 2.22 cm/s for pulsatile flow. The mean difference between duplicate measurements was 0 ± 1.4 cm/s. In in vivo experiments, the flow (product of velocity and lumen cross-sectional area that is also measured by the conductance catheter) was determined in both normal and stenotic vessels and the mean difference between the proposed method and flow probe was -1 ± 12 ml/min (flow ranged from 10 to 130 ml/min). For CFR, the mean difference between the two methods was 0.06 ± 0.28 (range of 1 to 3). Our results demonstrate the reproducibility and accuracy of velocity and CFR measurements with a conductance catheter by use of a standard saline injection. The ability of the combined measurement of coronary lumen area (as previously validated) and current velocity and CFR measurements provides an integrative diagnostic tool for interventional cardiology.

Structural coronary microcirculation abnormalities are important prognostic determinants in clinical settings. However, an assessment of microvascular resistance (MR) requires a velocity wire. A first-pass distribution analysis technique to measure volumetric blood flow has been previously validated. The aim of this study was the in vivo validation of the MR measurement technique using first-pass distribution analysis. Twelve anesthetized swine were instrumented with a transit-time ultrasound flow probe on the proximal segment of the left anterior descending coronary artery (LAD). Microspheres were injected into the LAD to create a model of microvascular dysfunction. Adenosine (400 μg·kg(-1)·min(-1)) was used to produce maximum hyperemia. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. Volumetric blood flow measurements (Q(a)) were made using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. Blood flow from the flow probe (Q(p)), coronary pressure (P(a)), and right atrium pressure (P(v)) were continuously recorded. Flow probe-based normalized MR (NMR(p)) and angiography-based normalized MR (NMR(a)) were calculated using Q(p) and Q(a), respectively. In 258 measurements, Q(a) showed a strong correlation with the gold standard Q(p) (Q(a) = 0.90 Q(p) + 6.6 ml/min, r(2) = 0.91, P < 0.0001). NMR(a) correlated linearly with NMR(p) (NMR(a) = 0.90 NMR(p) + 0.02 mmHg·ml(-1)·min(-1), r(2) = 0.91, P < 0.0001). Additionally, the Bland-Altman analysis showed a close agreement between NMR(a) and NMR(p). In conclusion, a technique based on angiographic image data for quantifying NMR was validated using a swine model. This study provides a method to measure NMR without using a velocity wire, which can potentially be used to evaluate microvascular conditions during coronary arteriography.

Remodeling of right coronary artery (RCA) occurs during right ventricular hypertrophy (RVH) induced by banding of the pulmonary artery (PA). The effect of RVH on RCA endothelial function and reactive oxygen species (ROS) in vessel wall remains unclear. A swine RVH model (n = 12 pigs) induced by PA banding was used to study RCA endothelial function and ROS level. To obtain longitudinal coronary hemodynamic and geometric data, digital subtraction angiography was used during the progression of RVH. Blood flow in the RCA increased by 82% and lumen diameter of RCA increased by 22% over a 4-wk period of RVH. The increase in blood flow and the commensurate increase in diameter resulted in a constant wall shear stress in RCA throughout the RVH period. ROS was elevated by ∼100% in RCA after 4 wk of PA banding. The expressions of p47(phox), NADPH oxidase (NOX1, NOX2, and NOX4) were upregulated in the range of 20-300% in RCA of RVH. The endothelial function was compromised in RCA of RVH as attributed to insufficient endothelial nitric oxide synthase cofactor tetrahydrobiopterin. In vivo angiographic analysis suggests an increased basal tone in the RCA during RVH. In conclusion, stretch due to outward remodeling of RCA during RVH (at constant wall shear stress), similar to vessel stretch in hypertension, appears to induce ROS elevation, endothelial dysfunction, and an increase in basal tone.