Detection of Pacemaker and Identification of MRI-conditional Pacemaker Based on Deep-learning Convolutional Neural Networks to Improve Patient Safety.

With the increased availability of magnetic resonance imaging (MRI) and a progressive rise in the frequency of cardiac device implantation, there is an increased chance that patients with implanted cardiac devices require MRI examination during their lifetime. Though MRI is generally contraindicated in patients who have undergone pacemaker implantation with electronic circuits, the recent introduction of MR Conditional pacemaker allows physicians to take advantage of MRI to assess these patients during diagnosis and treatment. When MRI examinations of patients with pacemaker are requested, physicians must confirm whether the device is a conventional pacemaker or an MR Conditional pacemaker by reviewing chest radiographs or the electronic medical records (EMRs). The purpose of this study was to evaluate the utility of a deep convolutional neural network (DCNN) trained to detect pacemakers on chest radiographs and to determine the device's subclassification. The DCNN perfectly detected pacemakers on chest radiographs and the accuracy of the subclassification of pacemakers using the internal and external test datasets were 100.0% (n = 106/106) and 90.1% (n = 279/308). The DCNN can be applied to the radiologic workflow for double-checking purposes, thereby improving patient safety during MRI and preventing busy physicians from making errors.

Quality of science and reporting for radiomics in cardiac magnetic resonance imaging studies: a systematic review.

OBJECTIVES: To evaluate the quality of radiomics studies using cardiac magnetic resonance imaging (CMR) according to the radiomics quality score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, and the standards defined by the Image Biomarker Standardization Initiative (IBSI) and identify areas needing improvement. MATERIALS AND METHODS: PubMed and Embase were searched to identify radiomics studies using CMR until March 10, 2021. Of the 259 identified articles, 32 relevant original research articles were included. Studies were scored according to the RQS, TRIPOD guidelines, and IBSI standards by two cardiac radiologists. RESULTS: The mean RQS was 14.3% of the maximum (5.16 out of 36). RQS were low for the demonstration of validation (-60.6%), calibration statistics (1.6%), potential clinical utility (3.1%), and open science (3.1%) items. No study conducted a phantom study or cost-effectiveness analysis. The adherence to TRIPOD guidelines was 55.9%. Studies were deficient in reporting title (3.1%), stating objective in abstract and introduction (6.3% and 9.4%), missing data (0%), discrimination/calibration (3.1%), and how to use the prediction model (3.1%). According to the IBSI standards, non-uniformity correction, image interpolation, grey-level discretization, and signal intensity normalization were performed in two (6.3%), four (12.5%), six (18.8%), and twelve (37.5%) studies, respectively. CONCLUSION: The quality of radiomics studies using CMR is suboptimal. Improvements are needed in the areas of validation, calibration, clinical utility, and open science. Complete reporting of study objectives, missing data, discrimination/calibration, how to use the prediction model, and preprocessing steps are necessary. KEY POINTS: • The quality of science in radiomics studies using CMR is currently inadequate. • RQS were low for validation, calibration, clinical utility, and open science; no study conducted a phantom study or cost-effectiveness analysis. • In stating the study objective, missing data, discrimination/calibration, how to use the prediction model, and preprocessing steps, improvements are needed.

Phantom-based correction for standardization of myocardial native T1 and extracellular volume fraction in healthy subjects at 3-Tesla cardiac magnetic resonance imaging.

OBJECTIVES: To investigate the effect of the phantom-based correction method for standardizing myocardial native T1 and extracellular volume fraction (ECV) in healthy subjects. METHODS: Seventy-one healthy asymptomatic adult (≥ 20 years) volunteers of five different age groups (34 men and 37 women, 45.5 ± 15.5 years) were prospectively enrolled in three academic hospitals. Cardiac MRI including Modified Look - Locker Inversion recovery T1 mapping sequence was performed using a 3-Tesla system with a different type of scanner for each hospital. Native T1 and ECV were measured in the short-axis T1 map and analyzed for mean values of the 16 entire segments. The myocardial T1 value of each subject was corrected based on the site-specific equation derived from the T1 Mapping and ECV Standardization phantom. The global native T1 and ECV were compared between institutions before and after phantom-based correction, and the variation in native T1 and ECV among institutions was assessed using a coefficient of variation (CoV). RESULTS: The global native T1 value significantly differed between the institutions (1198.7 ± 32.1 ms, institution A; 1217.7 ± 39.9 ms, institution B; 1232.7 ± 31.1 ms, institution C; p = 0.002), but the mean ECV did not (26.6-27.5%, p = 0.355). After phantom-based correction, the global native T1 and ECV were 1289.7 ± 32.4 ms and 25.0 ± 2.7%, respectively, and CoV for native T1 between the three institutions decreased from 3.0 to 2.5%. The corrected native T1 value did not significantly differ between institutions (1284.5 ± 31.5 ms, institution A; 1296.5 ± 39.1 ms, institution B; 1291.3 ± 29.3 ms, institution C; p = 0.440), and neither did the ECV (24.4-25.9%, p = 0.078). CONCLUSIONS: The phantom-based correction method can provide standardized reference T1 values in healthy subjects. KEY POINTS: • After phantom-based correction, the global native T1 of 16 entire myocardial segments on 3-T cardiac MRI is 1289.4 ± 32.4 ms, and the extracellular volume fraction was 25.0 ± 2.7% for healthy subjects. • After phantom - based correction was applied, the differences in the global native T1 among institutions became insignificant, and the CoV also decreased from 3.0 to 2.5%.

The image quality and diagnostic accuracy of T1-mapping-based synthetic late gadolinium enhancement imaging: comparison with conventional late gadolinium enhancement imaging in real-life clinical situation.

BACKGROUNDS: Synthetic late gadolinium enhancement (LGE) images are less sensitive to inversion time (TI) and robust to motion artifact, because it is generated retrospectively by post-contrast T1-mapping images. To explore the clinical applicability of synthetic LGE, we investigated the image quality and diagnostic accuracy of synthetic LGE images, in comparison to that of conventional LGE for various disease groups. METHOD AND MATERIALS: From July to November 2019, a total of 98 patients who underwent cardiovascular magnetic resonance imaging (CMR), including LGE and T1-mapping sequences, with suspicion of myocardial abnormality were retrospectively included. Synthetic magnitude inversion-recovery (IR) and phase-sensitive IR (PSIR) images were generated through calculations based on the post-contrast T1-mapping sequence. Three cardiothoracic radiologists independently analyzed the image quality of conventional and synthetic LGE images on an ordinal scale with per-segment basis and the image qualities were compared with chi-square test. The agreement of LGE detection was analyzed on per-patient and per-segment basis with Cohen's kappa test. In addition, the LGE area and percentage were semi-quantitatively analyzed for LGE positive ischemic (n = 14) and hypertrophic cardiomyopathy (n = 13) subgroups by two cardiothoracic radiologists. The difference of quantified LGE area and percentage between conventional and synthetic LGE images were assessed with Mann-Whitney U-test and the inter-reader agreement was assessed with Bland-Altman analysis. RESULTS: The image quality of synthetic images was significantly better than conventional images in both magnitude IR and PSIR through all three observers (P < 0.001, all). The agreements of per-patient and per-segment LGE detection rates were excellent (kappa = 0.815-0.864). The semi-quantitative analysis showed no significant difference in the LGE area and percentage between conventional and synthetic LGE images. In the inter-reader agreement showed only small systematic differences in both magnitude IR and PSIR and synthetic LGE images showed smaller systematic biases compared to conventional LGE images. CONCLUSION: Compared to conventional LGE images, synthetic LGE images have better image quality in real-life clinical situation.

Synthetic Extracellular Volume Fraction Derived Using Virtual Unenhanced Attenuation of Blood on Contrast-Enhanced Cardiac Dual-Energy CT in Nonischemic Cardiomyopathy.

BACKGROUND. Current methods for calculating the myocardial extracellular volume (ECV) fraction require blood sampling to determine the serum hematocrit. Synthetic hematocrit and thus synthetic ECV may be derived using unenhanced attenuation of blood. By use of virtual unenhanced (VUE) attenuation of blood, contrast-enhanced dual-energy CT (DECT) may allow synthetic ECV calculations without unenhanced acquisition. OBJECTIVE. The purpose of this study was to compare synthetic ECV calculated using synthetic hematocrit derived from VUE images and conventional ECV calculated using serum hematocrit, both of which were obtained by contrast-enhanced DECT, with ECV derived from MRI used as the reference standard. METHODS. This retrospective study included 51 patients (26 men and 25 women; mean age, 59.9 ± 15.6 [SD] years) with nonischemic cardiomyopathy who, as part of an earlier prospective investigation, underwent equilibrium phase contrast-enhanced cardiac DECT and cardiac MRI and had serum hematocrit measured within 6 hours of both tests. A separate retrospective sample of 198 patients who underwent contrast-enhanced thoracic DECT performed on the same day for suspected pulmonary embolism and serum hematocrit measurement was identified to derive a synthetic hematocrit formula using VUE attenuation of blood by linear regression analysis. In the primary sample, two radiologists independently used DECT iodine maps to obtain the conventional ECV using serum hematocrit and the synthetic ECV using synthetic hematocrit based on the independently derived formula. The concordance correlation coefficient (CCC) was computed between conventional ECV and synthetic ECV from DECT. Conventional ECV and synthetic ECV from DECT were compared with the ECV derived from MRI in Bland-Altman analyses. RESULTS. In the independent sample, the linear regression formula for synthetic hematocrit was as follows: synthetic hematocrit = 0.85 × (VUE attenuation of blood) - 5.40. In the primary sample, the conventional ECV and synthetic ECV from DECT showed excellent agreement (CCC, 0.95). Bland-Altman analysis showed a small bias of -0.44% (95% limits of agreement, -5.10% to 4.22%) between MRI-derived ECV and conventional ECV from DECT as well as a small bias of -0.78% (95% limits of agreement, -5.25% to 3.69%) between MRI-derived ECV and synthetic ECV from DECT. CONCLUSION. Synthetic ECV and conventional ECV derived from DECT show excel lent agreement and a comparable association with ECV derived from cardiac MRI. CLINICAL IMPACT. Synthetic hematocrit from VUE attenuation of blood may allow myocardial tissue characterization on DECT without the inconvenience of blood sampling.

Comparison of artery-based methods for ordinal grading of coronary artery calcium on low-dose chest computed tomography.

OBJECTIVES: To identify the optimal artery-based method for ordinal grading of coronary artery calcium (CAC) on non-electrocardiogram (ECG)-gated low-dose chest computed tomography (LDCT) among three methods. METHODS: A total of 120 asymptomatic subjects who underwent both LDCT and ECG-gated calcium scoring CT on the same day were retrospectively enrolled. Three cardiothoracic radiologists independently assessed CAC severity on LDCT (1.25-mm and 2.5-mm slice thickness) and classified it into four categories (none, mild, moderate, or severe) using three artery-based ordinal scoring methods (extent-based scoring, Weston scoring, and length-based scoring). Inter- and intra-observer CAC severity agreements of each method were assessed by Fleiss kappa statistics. Agreements between each method and ECG-gated calcium scoring CT were assessed by weighted kappa statistics. RESULTS: The inter-observer agreement was highest with length-based method for both 1.25-mm (Fleiss kappa 0.735 for extent-based method, 0.801 for Weston score, and 0.813 for length-based method) and 2.5-mm slice thickness evaluation (Fleiss kappa 0.755 for extent-based method, 0.776 for Weston score, and 0.833 for extent-based method). Agreement across the three grading methods for the same observer was poor to moderate on 1.25-mm (Fleiss kappa 0.379-0.441) and moderate on 2.5-mm thickness evaluation (Fleiss kappa 0.427-0.461). Agreement of CAC severity between each method and ECG-gated calcium scoring CT was highest with the length-based method for all three observers on both 1.25-mm (weighted kappa 0.773-0.786) and 2.5-mm (weighted kappa 0.794-0.825) LDCT images. CONCLUSION: Among the three artery-based ordinal grading methods, the length-based method appears to be the most reliable for evaluating CAC on non-ECG-gated LDCT. KEY POINTS: • The length-based method showed the highest inter-observer agreement and the highest agreement with the ECG-gated calcium scoring CT, compared with the extent-based method and the Weston score.

Differentiation of left atrial appendage thrombus from circulatory stasis using cardiac CT radiomics in patients with valvular heart disease.

OBJECTIVES: To determine whether quantitative radiomic features from cardiac CT could differentiate the left atrial appendage (LAA) thrombus from circulatory stasis in patients with valvular heart disease. METHODS: Ninety-five consecutive patients with valvular heart disease and filling defects in LAA on two-phase cardiac CT from March 2016 to August 2018 were retrospectively enrolled and classified as having thrombus or stasis by transesophageal echocardiography or cardiac surgery. The ratio of Hounsfield units in the filling defects to those in the ascending aorta (AA) was calculated on early- and late-phase CT (LAA/AAE and LAA/AAL, respectively). Radiomic features were extracted from semi-automated three-dimensional segmentation of the filling defect on early-phase CT. The diagnostic ability of radiomic features for differentiating thrombus from stasis was assessed and compared to LAA/AAE and LAA/AAL by comparing the AUC of ROC curves. Diagnostic performances of CT attenuation ratios and radiomic features were validated with an independent validation set. RESULTS: Thrombus was diagnosed in 25 cases and stasis in 70. Sixty-eight radiomic features were extracted. Values of 8 wavelet-transformed features were lower in thrombus than in stasis (p < 0.001). The AUC value of a radiomic feature, wavelet_LHL, for diagnosing thrombus was 0.78, which was higher than that of LAA/AAE (AUC = 0.54, p = 0.025) and similar to that of LAA/AAL (AUC = 0.76, p = 0.773). In the validation set, the AUC of wavelet_LHL was 0.71, which was higher than that of LAA/AAE (AUC = 0.57, p = 0.391) and similar to that of LAA/AAL (AUC = 0.75, p = 0.707). CONCLUSIONS: Quantitative radiomic features from the early phase of cardiac CT may help diagnose LAA thrombus in patients with valvular heart disease. KEY POINTS: • Wavelet-transformed grey-level non-uniformity values from radiomic analysis are significantly lower for LAA thrombus than for circulatory stasis. • Radiomic features may have an additional value for differentiating LAA thrombus from circulatory stasis when interpreting single-phase cardiac CT. • Radiomic features extracted from single-phase images may show similar diagnostic ability as conventional quantitative analysis from two-phase images.

Machine learning in cardiovascular radiology: ESCR position statement on design requirements, quality assessment, current applications, opportunities, and challenges.

Machine learning offers great opportunities to streamline and improve clinical care from the perspective of cardiac imagers, patients, and the industry and is a very active scientific research field. In light of these advances, the European Society of Cardiovascular Radiology (ESCR), a non-profit medical society dedicated to advancing cardiovascular radiology, has assembled a position statement regarding the use of machine learning (ML) in cardiovascular imaging. The purpose of this statement is to provide guidance on requirements for successful development and implementation of ML applications in cardiovascular imaging. In particular, recommendations on how to adequately design ML studies and how to report and interpret their results are provided. Finally, we identify opportunities and challenges ahead. While the focus of this position statement is ML development in cardiovascular imaging, most considerations are relevant to ML in radiology in general. KEY POINTS: • Development and clinical implementation of machine learning in cardiovascular imaging is a multidisciplinary pursuit. • Based on existing study quality standard frameworks such as SPIRIT and STARD, we propose a list of quality criteria for ML studies in radiology. • The cardiovascular imaging research community should strive for the compilation of multicenter datasets for the development, evaluation, and benchmarking of ML algorithms.

Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic changes.

BACKGROUND: Chemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity. METHODS: Rat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed. RESULTS: Five control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01).  Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores) CONCLUSIONS: Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

Serial T1 mapping of right ventricle in pulmonary hypertension: comparison with histology in an animal study.

BACKGROUND: Right ventricular (RV) free wall fibrosis is an important component of adverse remodeling with RV dysfunction in pulmonary hypertension (PH). However, no previous reports have compared cardiovascular magnetic resonance (CMR) findings and histological analysis for RV free wall fibrosis in PH. We aimed to assess the feasibility of CMR T1 mapping with extracellular volume fraction (ECV) for evaluating the progression of RV free wall fibrosis in PH, and compared imaging findings to histological collagen density through an animal study. METHODS: Among 42 6-week-old Wistar male rats, 30 were classified according to disease duration (baseline before monocrotaline injection, and 2, 4, 6 and 8 weeks after injection) and 12 were used to control for aging (4 and 8 weeks after the baseline). We obtained pre and post-contrast T1 maps for native T1 and ECV of RV and left ventricular (LV) free wall for six animals in each disease-duration group. Collagen density of RV free wall was calculated with Masson's trichrome staining. The Kruskall-Wallis test was performed to compare the groups. Native T1 and ECV to collagen density were analyzed with Spearman's correlation. RESULTS: The mean values of native T1, ECV and collagen density of the RV free wall at baseline were 1541 ± 33 ms, 17.2 ± 1.3%, and 4.7 ± 0.5%, respectively. The values of RV free wall did not differ according to aging (P = 0.244, 0.504 and 0.331, respectively). However, the values significantly increased according to disease duration (P < 0.001 for all). Significant correlations were observed between native T1 and collagen density (r = 0.770, P < 0.001), and between ECV and collagen density for the RV free wall (r = 0.815, P < 0.001) in PH. However, there was no significant difference in native T1 and ECV values for the LV free wall according to the disease duration from the baseline (P = 0.349 and 0.240, respectively). CONCLUSIONS: We observed significantly increased values for native T1 and ECV of the RV free wall without significant increase of the LV free wall according to the disease duration of PH, and findings were well correlated with histological collagen density.

Prognostic Value of Coronary Artery Disease-Reporting and Data System Score for Major Adverse Cardiac Events in Patients Attending the Emergency Department With Acute Chest Pain.

OBJECTIVE: This study aimed to compare the prognostic performance of Coronary Artery Disease (CAD)-Reporting and Data System (CAD-RADS) score with those of clinical risk factors and the extent of CAD classification for predicting major adverse cardiac events in emergency department patients. METHODS: A total of 779 patients with acute chest pain at low to intermediate risk for CAD underwent cardiac computed tomography angiography. The primary end point was early and late major adverse cardiac events. We developed the following models: model 1, clinical risk factors; model 2, clinical risk factors and CAD-RADS scores; model 3, clinical risk factors and extent of CAD. RESULTS: The C-statistics revealed that both CAD-RADS score and CAD extent improved risk stratification over the clinical risk factors (C-index for early events: C-index: 0.901 vs 0.814 and 0.911 vs 0.814; C-index for late events: 0.897 vs 0.808 and 0.905 vs 0.808; all P < 0.05). CONCLUSIONS: The CAD-RADS score had additional risk prediction benefits over clinical risk factors for emergency department patients.

Relationship between Coronary Artery Calcification and Central Chorioretinal Thickness in Patients with Subclinical Atherosclerosis.

PURPOSE: To evaluate the relationship between coronary artery calcification and subfoveal thicknesses of individual chorioretinal layers in subjects with subclinical atherosclerosis by using enhanced-depth imaging optical coherence tomography. METHODS: In this retrospective, noninterventional, cross-sectional study, we included 193 eyes from 193 subjects and divided them into three cardiovascular (CV) risk groups based on coronary artery calcification (CAC) scores calculated from cardiac-gated computed tomography: low (CAC = 0; n = 77), intermediate (CAC = 1-300; n = 83), and high (CAC >300; n = 33). Central macula individual retinal layer thicknesses and subfoveal choroidal thickness were measured and compared among groups. Multivariate linear regression was used to evaluate associations of subfoveal choroidal thickness or central retinal thickness with CAC scores. RESULTS: Average subfoveal choroidal thickness differed significantly among low, intermediate, and high CV risk groups (all p < 0.05). There were no statistically significant changes in segmented retinal layer thickness of the central macula. Multivariate regression analyses showed that higher CAC scores were significantly negatively associated with subfoveal choroidal thickness (ß = -2.169, p < 0.001). CONCLUSIONS: Higher CAC scores were significantly associated with subfoveal choroidal thinning in subjects with subclinical atherosclerosis. Prominent reductions in the subfoveal choroidal layer could provide a useful biomarker for predicting CV risk in patients of advanced age with subclinical atherosclerosis.

Deep Convolutional Neural Network-based Software Improves Radiologist Detection of Malignant Lung Nodules on Chest Radiographs.

Background Multicenter studies are required to validate the added benefit of using deep convolutional neural network (DCNN) software for detecting malignant pulmonary nodules on chest radiographs. Purpose To compare the performance of radiologists in detecting malignant pulmonary nodules on chest radiographs when assisted by deep learning-based DCNN software with that of radiologists or DCNN software alone in a multicenter setting. Materials and Methods Investigators at four medical centers retrospectively identified 600 lung cancer-containing chest radiographs and 200 normal chest radiographs. Each radiograph with a lung cancer had at least one malignant nodule confirmed by CT and pathologic examination. Twelve radiologists from the four centers independently analyzed the chest radiographs and marked regions of interest. Commercially available deep learning-based computer-aided detection software separately trained, tested, and validated with 19 330 radiographs was used to find suspicious nodules. The radiologists then reviewed the images with the assistance of DCNN software. The sensitivity and number of false-positive findings per image of DCNN software, radiologists alone, and radiologists with the use of DCNN software were analyzed by using logistic regression and Poisson regression. Results The average sensitivity of radiologists improved (from 65.1% [1375 of 2112; 95% confidence interval {CI}: 62.0%, 68.1%] to 70.3% [1484 of 2112; 95% CI: 67.2%, 73.1%], P < .001) and the number of false-positive findings per radiograph declined (from 0.2 [488 of 2400; 95% CI: 0.18, 0.22] to 0.18 [422 of 2400; 95% CI: 0.16, 0.2], P < .001) when the radiologists re-reviewed radiographs with the DCNN software. For the 12 radiologists in this study, 104 of 2400 radiographs were positively changed (from false-negative to true-positive or from false-positive to true-negative) using the DCNN, while 56 of 2400 radiographs were changed negatively. Conclusion Radiologists had better performance with deep convolutional network software for the detection of malignant pulmonary nodules on chest radiographs than without. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Jacobson in this issue.

Cardiotoxicity evaluation using magnetic resonance imaging in breast Cancer patients (CareBest): study protocol for a prospective trial.

BACKGROUND: Cardiovascular disease is second only to cancer recurrence as a determinant of lifespan in cancer survivors, and cancer therapy-related cardiac dysfunction is a clinically important risk factor. We aim to investigate the use of cardiac magnetic resonance imaging (MRI) to evaluate early tissue changes and perform functional assessment of chemo- and radiation-induced cardiotoxicity and to identify MRI prognostic indicators of cardiotoxicity in breast cancer patients. METHODS: A 3-min cardiac imaging protocol will be added to the breast MRI examination to diagnose cardiotoxicity in breast cancer patients. Standardized MRI-based evaluation of breast cancer and the left ventricular myocardium will be performed at baseline and at 3, 6, and 12 months and 2 years or more after cancer treatment. We will analyze both ventricular volume and ejection fraction (EF), strain of left ventricle (LV), native T1, extracellular volume fraction (ECV), and T2 values acquired in the mid LV. DISCUSSION: The primary result of this study will be the comparison of the prognostic value of MRI parameters (native T1, ECV, both ventricular systolic function and LV strain) for cardiotoxicity. The endpoint is defined as the occurrence of a major adverse cardiac event (MACE). The secondary outcome will be an assessment of the temporal relationships between contractile dysfunction and microstructural injury over 4 years using MRI. This study will assess the usefulness of quantitative MRI to diagnose cardiotoxicity and will clarify the temporal relationships between contractile dysfunction and microstructural injury of the LV myocardium using MRI during breast cancer treatment. TRIAL REGISTRATION: The protocol was registered at clinicaltrials.gov (Clinical trial no. NCT03301389) on October 4, 2017.

HIV-1 Tat enhances purinergic P2Y4 receptor signaling to mediate inflammatory cytokine production and neuronal damage via PI3K/Akt and ERK MAPK pathways.

BACKGROUND: HIV-associated neurocognitive disorders (HANDs) afflict more than half of HIV-1-positive individuals. The transactivator of transcription (Tat) produced by HIV virus elicits inflammatory process and is a major neurotoxic mediator that induce neuron damage during HAND pathogenesis. Activated astrocytes are important cells involved in neuroinflammation and neuronal damage. Purinergic receptors expressed in astrocytes participate in a positive feedback loop in virus-induced neurotoxicity. Here, we investigated that whether P2Y4R, a P2Y receptor subtype, that expressed in astrocyte participates in Tat-induced neuronal death in vitro and in vivo. METHODS: Soluble Tat protein was performed to determine the expression of P2Y4R and proinflammatory cytokines in astrocytes using siRNA technique via real-time PCR, Western blot, and immunofluorescence assays. Cytometric bead array was used to measure proinflammatory cytokine release. The TUNEL staining and MTT cell viability assay were analyzed for HT22 cell apoptosis and viability, and the ApopTag® peroxidase in situ apoptosis detection kit and cresyl violet staining for apoptosis and death of hippocampal neuron in vivo. RESULTS: We found that Tat challenge increased the expression of P2Y4R in astrocytes. P2Y4R signaling in astrocytes was involved in Tat-induced inflammatory cytokine production via PI3K/Akt- and ERK1/2-dependent pathways. Knockdown of P2Y4R expression significantly reduced inflammatory cytokine production and relieved Tat-mediated neuronal apoptosis in vitro. Furthermore, in vivo challenged with Tat, P2Y4R knockdown mice showed decreased inflammation and neuronal damage, especially in hippocampal CA1 region. CONCLUSIONS: Our data provide novel insights into astrocyte-mediated neuron damage during HIV-1 infection and suggest a potential therapeutic target for HANDs.

Utility of Dual-Energy CT-based Monochromatic Imaging in the Assessment of Myocardial Delayed Enhancement in Patients with Cardiomyopathy.

Purpose To investigate the diagnostic utility of dual-energy computed tomography (CT)-based monochromatic imaging for myocardial delayed enhancement (MDE) assessment in patients with cardiomyopathy. Materials and Methods The institutional review board approved this prospective study, and informed consent was obtained from all participants who were enrolled in the study. Forty patients (27 men and 13 women; mean age, 56 years ± 15 [standard deviation]; age range, 22-81 years) with cardiomyopathy underwent cardiac magnetic resonance (MR) imaging and dual-energy CT. Conventional (120-kV) and monochromatic (60-, 70-, and 80-keV) images were reconstructed from the dual-energy CT acquisition. Subjective quality score, contrast-to-noise ratio (CNR), and beam-hardening artifacts were compared pairwise with the Friedman test at post hoc analysis. With cardiac MR imaging as the reference standard, diagnostic performance of dual-energy CT in MDE detection and its predictive ability for pattern classification were compared pairwise by using logistic regression analysis with the generalized estimating equation in a per-segment analysis. The Bland-Altman method was used to find agreement between cardiac MR imaging and CT in MDE quantification. Results Among the monochromatic images, 70-keV CT images resulted in higher subjective quality (mean score, 3.38 ± 0.54 vs 3.15 ± 0.43; P = .0067), higher CNR (mean, 4.26 ± 1.38 vs 3.93 ± 1.33; P = .0047), and a lower value for beam-hardening artifacts (mean, 3.47 ± 1.56 vs 4.15 ± 1.67; P < .0001) when compared with conventional CT. When compared with conventional CT, 70-keV CT showed improved diagnostic performance for MDE detection (sensitivity, 94.6% vs 90.4% [P = .0032]; specificity, 96.0% vs 94.0% [P = .0031]; and accuracy, 95.6% vs 92.7% [P < .0001]) and improved predictive ability for pattern classification (subendocardial, 91.5% vs 84.3% [P = .0111]; epicardial, 94.3% vs 73.5% [P = .0001]; transmural, 93.0% vs 77.7% [P = .0018]; mesocardial, 85.4% vs 69.2% [P = .0047]; and patchy. 84.4% vs 78.4% [P = .1514]). For MDE quantification, 70-keV CT showed a small bias 0.1534% (95% limits of agreement: -4.7013, 5.0080). Conclusion Dual-energy CT-based 70-keV monochromatic images improve MDE assessment in patients with cardiomyopathy via improved image quality and CNR and reduced beam-hardening artifacts when compared with conventional CT images. © RSNA, 2017 Online supplemental material is available for this article.

Myocardial Extracellular Volume Fraction and Change in Hematocrit Level: MR Evaluation by Using T1 Mapping in an Experimental Model of Anemia.

Purpose To evaluate the effect of changes in hematocrit level on myocardial extracellular volume (ECV) fraction, as quantified with cardiac magnetic resonance (MR) imaging in an animal model. Materials and Methods Thirteen adult male Sprague-Dawley rats underwent cardiac MR imaging before and after induction of anemia. MR imaging procedures, including unenhanced and contrast material-enhanced T1 mapping, were performed by using a saturation recovery Look-Locker sequence with a 9.4-T unit. An optimized T1 mapping sequence was established in the phantom study. Systolic function of the left ventricle (LV) was calculated from the cine images. Native and postcontrast T1 values of the LV myocardium at the midcavity level and LV blood pool, partition coefficients, and ECV were calculated. Histopathologic examination of the heart was performed after sacrifice. Intergroup comparison of variables was performed with the paired t test. Results The postanemia models exhibited lower hematocrit levels, postcontrast T1 values of the LV pool, and partition coefficients (mean, 45.7% ± 5.2 [standard deviation]; 563.8 msec ± 155.7; and 29.2 ± 3.5, respectively) than did the preanemia models (mean, 59.0% ± 4.1; 690.2 msec ± 109.7; and 38.2 ± 4.4, respectively) (P < .05 for all comparisons). There were no differences between the pre- and postanemia groups in terms of LV ejection fraction (mean, 72.7% ± 2.1 vs 73.2% ± 4.7; P = .78) and ECV (mean, 15.5% ± 2.0 vs 16.0% ± 1.9; P = .24). Conclusion Myocardial ECV measured with contrast-enhanced T1 mapping cardiac MR imaging did not significantly change despite changes in hematocrit level in anemic rat models. Extrapolation of this finding from animal models to human subjects suggests that ECV measured with MR imaging could be a robust parameter in anemic patients.

Accuracy of computed tomography for selecting the revascularization method based on SYNTAX score II.

OBJECTIVES: The application of SYNTAX score II based on coronary CT angiography (CCTA) for selecting further treatment options has not been studied. This study aimed to investigate the diagnostic performance of CCTA combined with SYNTAX score II for selecting the revascularization method compared with invasive coronary angiography (ICA) based on 2014 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines. METHODS: From January-May 2011, 160 patients who underwent both CCTA and ICA within 30 interval days were included. The diagnostic performance of CCTA, CCTA plus CT-SYNTAX score I and CT-SYNTAX score II was analysed using ICA counterparts as references. RESULTS: Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CCTA plus CT-SYNTAX I for selecting coronary artery bypass grafting (CABG) candidates using ICA plus ICA-SYNTAX I as reference, were 70.6 %, 95.8 %, 66.7 %, 96.5 % and 93.1 %, respectively. The diagnostic performance of CCTA plus CT-SYNTAX II showed improvement with values of 83.3 %, 97.3 %, 71.4 %, 98.6 % and 96.3 %, respectively, using ICA plus ICA-SYNTAX II as reference. CONCLUSIONS: CCTA combined with CT-SYNTAX score II is an accurate method for selecting CABG surgery candidates compared with ICA-SYNTAX score II. KEY POINTS: • SYNTAX plus CCTA can be highly specific for selecting the revascularization method. • SYNTAX II was complemented by including clinical considerations to SYNTAX I. • CCTA plus CT-SYNTAX II is an accurate method for selecting CABG candidates.

Adverse Prognostic CT Findings for Patients With Advanced Lung Adenocarcinoma Receiving First-Line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapy.

OBJECTIVE: The purpose of this study is to investigate adverse prognostic CT findings in patients with advanced-stage lung adenocarcinoma who are receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy as first-line therapy. MATERIALS AND METHODS: We included 199 patients (71 men and 128 women; mean ± SD age, 64.3 ± 11.2 years) with stage IIIB or IV lung adenocarcinoma who received first-line EGFR-TKI therapy between January 2009 and December 2015. Clinical findings and imaging parameters on CT images obtained before TKI therapy were analyzed, including tumor size, TNM category according to the seventh edition of the American Joint Committee on Cancer lung cancer TNM staging system, tumor type, the presence of cavity or necrosis, pleural effusion, and metastasis to pleura, lung, and distant organs. Response evaluation was performed according to the Response Evaluation Criteria in Solid Tumor version 1.1 guidelines. Correlation of clinical and radiologic findings with durations of progression-free survival (PFS) and overall survival (OS) was evaluated using a Cox proportional hazard model. RESULTS: Pleural effusion (hazard ratio [HR], 2.095; 95% CI, 1.394-3.147; p < 0.001) and an N2 or N3 tumor category (HR, 2.145; 95% CI, 1.280-3.594; p = 0.004) were significantly associated with a short PFS duration in multivariate analysis. Older age (HR, 1.040; 95% CI, 1.014-1.067; p = 0.002), an N2 or N3 tumor category (HR, 2.427; 95% CI, 1.068-5.518; p = 0.034), pleural effusion (HR, 1.903; 95% CI, 1.105-3.276; p = 0.020), and distant metastasis (HR, 2.795; 95% CI, 1.356-5.765; p = 0.005) were associated with a short OS duration in multivariate analysis. CONCLUSION: Pre-TKI therapy CT findings of pleural effusion and high N-category tumors are associated with short durations of PFS and OS in patients with lung adenocarcinoma who are receiving EGFR-TKI therapy.

Diagnostic Performance of a Novel Coronary CT Angiography Algorithm: Prospective Multicenter Validation of an Intracycle CT Motion Correction Algorithm for Diagnostic Accuracy.

OBJECTIVE: Motion artifact can reduce the diagnostic accuracy of coronary CT angiography (CCTA) for coronary artery disease (CAD). The purpose of this study was to compare the diagnostic performance of an algorithm dedicated to correcting coronary motion artifact with the performance of standard reconstruction methods in a prospective international multicenter study. SUBJECTS AND METHODS: Patients referred for clinically indicated invasive coronary angiography (ICA) for suspected CAD prospectively underwent an investigational CCTA examination free from heart rate-lowering medications before they underwent ICA. Blinded core laboratory interpretations of motion-corrected and standard reconstructions for obstructive CAD (≥ 50% stenosis) were compared with ICA findings. Segments unevaluable owing to artifact were considered obstructive. The primary endpoint was per-subject diagnostic accuracy of the intracycle motion correction algorithm for obstructive CAD found at ICA. RESULTS: Among 230 patients who underwent CCTA with the motion correction algorithm and standard reconstruction, 92 (40.0%) had obstructive CAD on the basis of ICA findings. At a mean heart rate of 68.0 ± 11.7 beats/min, the motion correction algorithm reduced the number of nondiagnostic scans compared with standard reconstruction (20.4% vs 34.8%; p < 0.001). Diagnostic accuracy for obstructive CAD with the motion correction algorithm (62%; 95% CI, 56-68%) was not significantly different from that of standard reconstruction on a per-subject basis (59%; 95% CI, 53-66%; p = 0.28) but was superior on a per-vessel basis: 77% (95% CI, 74-80%) versus 72% (95% CI, 69-75%) (p = 0.02). The motion correction algorithm was superior in subgroups of patients with severely obstructive (≥ 70%) stenosis, heart rate ≥ 70 beats/min, and vessels in the atrioventricular groove. CONCLUSION: The motion correction algorithm studied reduces artifacts and improves diagnostic performance for obstructive CAD on a per-vessel basis and in selected subgroups on a per-subject basis.