Prognostic value of CT body composition analysis for 1-year mortality after transcatheter aortic valve replacement.

OBJECTIVES: To investigate the value of body composition indices derived from pre-procedural computed tomography (CT) in predicting 1-year mortality among patients who underwent transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: We assessed consecutive patients who underwent TAVR between June 2016 and December 2021 at a single academic medical center. Skeletal muscle and subcutaneous fat area at the T4, T12, and L3 levels on pre-procedural CT were measured. The association between body composition and 1-year mortality was evaluated using Cox proportional hazard regression analysis. RESULTS: Finally, 408 patients were included (185 men and 223 women; mean age, 81.7 ± 5.1 years; range, 62-98 years). Post-procedural death occurred in 13.2% of patients. The muscle-height index and fat-height index at the L3 level were more strongly correlated with those at the T12 level (r = 0.765, p < 0.001 and r = 0.932, p < 0.001, respectively) than with those at the T4 level (r = 0.535, p < 0.001 and r = 0.895, p < 0.001, respectively). The cumulative 1-year mortality rate was highest for patients with both sarcopenia and adipopenia (26%), followed by those with adipopenia only (17%), those with sarcopenia only (12%), and those with neither sarcopenia nor adipopenia (8%, p = 0.002). Multivariable analysis revealed that body composition at the T12 level was an independent risk factor for 1-year mortality (hazard ratio: 4.09, 95% confidence interval: 2.01-8.35) in patients with both sarcopenia and adipopenia (p < 0.001). CONCLUSION: Sarcopenia or adipopenia assessed with CT at the thoracic level may be valuable for stratifying 1-year all-cause mortality in patients who undergo TAVR. CLINICAL RELEVANCE STATEMENT: Skeletal muscle and subcutaneous fat mass indices at the level of T12, measured on pre-procedural CT, have value for risk stratification of 1-year all-cause mortality in patients who undergo transcatheter aortic valve replacement. KEY POINTS: Sarcopenia and adipopenia are associated with the prognosis of patients undergoing transcatheter aortic valve replacement. Body composition at the T12 level was an independent risk factor for 1-year all-cause mortality. Sarcopenia or adipopenia assessed at T12 with pre-procedural CT is valuable for risk stratification.

Importance of Local Ablative Therapies for Lung Metastases in Patients With Colorectal Cancer.

OBJECTIVE: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy. SUMMARY BACKGROUND DATA: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC. METHODS: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered. RESULTS: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased. CONCLUSIONS: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period.

Fully automatic coronary calcium scoring in non-ECG-gated low-dose chest CT: comparison with ECG-gated cardiac CT.

OBJECTIVES: To validate an artificial intelligence (AI)-based fully automatic coronary artery calcium (CAC) scoring system on non-electrocardiogram (ECG)-gated low-dose chest computed tomography (LDCT) using multi-institutional datasets with manual CAC scoring as the reference standard. METHODS: This retrospective study included 452 subjects from three academic institutions, who underwent both ECG-gated calcium scoring computed tomography (CSCT) and LDCT scans. For all CSCT and LDCT scans, automatic CAC scoring (CAC_auto) was performed using AI-based software, and manual CAC scoring (CAC_man) was set as the reference standard. The reliability and agreement of CAC_auto was evaluated and compared with that of CAC_man using intraclass correlation coefficients (ICCs) and Bland-Altman plots. The reliability between CAC_auto and CAC_man for CAC severity categories was analyzed using weighted kappa (κ) statistics. RESULTS: CAC_auto on CSCT and LDCT yielded a high ICC (0.998, 95% confidence interval (CI) 0.998-0.999 and 0.989, 95% CI 0.987-0.991, respectively) and a mean difference with 95% limits of agreement of 1.3 ± 37.1 and 0.8 ± 75.7, respectively. CAC_auto achieved excellent reliability for CAC severity (κ = 0.918-0.972) on CSCT and good to excellent but heterogenous reliability among datasets (κ = 0.748-0.924) on LDCT. CONCLUSIONS: The application of an AI-based automatic CAC scoring software to LDCT shows good to excellent reliability in CAC score and CAC severity categorization in multi-institutional datasets; however, the reliability varies among institutions. KEY POINTS: • AI-based automatic CAC scoring on LDCT shows excellent reliability with manual CAC scoring in multi-institutional datasets. • The reliability for CAC score-based severity categorization varies among datasets. • Automatic scoring for LDCT shows a higher false-positive rate than automatic scoring for CSCT, and most common causes of a false-positive are image noise and artifacts for both CSCT and LDCT.

Evaluation of fully automated commercial software for Agatston calcium scoring on non-ECG-gated low-dose chest CT with different slice thickness.

OBJECTIVES: To evaluate commercial deep learning-based software for fully automated coronary artery calcium (CAC) scoring on non-electrocardiogram (ECG)-gated low-dose CT (LDCT) with different slice thicknesses compared with manual ECG-gated calcium-scoring CT (CSCT). METHODS: This retrospective study included 567 patients who underwent both LDCT and CSCT. All LDCT images were reconstructed with a 2.5-mm slice thickness (LDCT2.5-mm), and 453 LDCT scans were reconstructed with a 1.0-mm slice thickness (LDCT1.0-mm). Automated CAC scoring was performed on CSCT (CSCTauto), LDCT1.0-mm, and LDCT2.5-mm images. The reliability of CSCTauto, LDCT1.0-mm, and LDCT2.5-mm was compared with manual CSCT scoring (CSCTmanual) using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Agreement, in CAC severity category, was analyzed using weighted kappa statistics. Diagnostic performance at various Agatston score cutoffs was also calculated. RESULTS: CSCTauto, LDCT1.0-mm, and LDCT2.5-mm demonstrated excellent agreement with CSCTmanual (ICC [95% confidence interval, CI]: 1.000 [1.000, 1.000], 0.937 [0.917, 0.952], and 0.955 [0.946, 0.963], respectively). The mean difference with 95% limits of agreement was lower with LDCT1.0-mm than with LDCT2.5-mm (19.94 [95% CI, -244.0, 283.9] vs. 45.26 [-248.2, 338.7]). Regarding CAC severity, LDCT1.0-mm achieved almost perfect agreement, and LDCT2.5-mm achieved substantial agreement (kappa [95% CI]: 0.809 [0.776, 0.838], 0.776 [0.740, 0.809], respectively). Diagnostic performance for detecting Agatston score ≥ 400 was also higher with LDCT1.0-mm than with LDCT2.5-mm (F1 score, 0.929 vs. 0.855). CONCLUSIONS: Fully automated CAC-scoring software with both CSCT and LDCT yielded excellent reliability and agreement with CSCTmanual. LDCT1.0-mm yielded more accurate Agatston scoring than LDCT2.5-mm using fully automated commercial software. KEY POINTS: • Total Agatston scores and all vessels of CSCTauto, LDCT1.0-mm, and LDCT2.5-mm demonstrated excellent agreement with CSCTmanual (all ICC > 0.85). • The diagnostic performance for detecting all Agatston score cutoffs was better with LDCT1.0-mm than with LDCT2.5-mm. • This automated software yielded a lower degree of underestimation compared with methods described in previous studies, and the degree of underestimation was lower with LDCT1.0-mm than with LDCT2.5-mm.

Coronary CTA for Acute Chest Pain in the Emergency Department: Comparison of 64-Detector-Row Single-Source and Third-Generation Dual-Source Scanners.

BACKGROUND. When coronary CTA is performed in the emergency department (ED), the use of a contemporary scanner with improved temporal resolution may eliminate the need to administer ß-blockers for heart rate (HR) control, thereby expediting workup. OBJECTIVE. The purpose of this study was to compare ED length of stay (LOS), image quality, frequency of nondiagnostic examinations, and other clinical outcomes between patients undergoing coronary CTA in the ED on a single-source CT (SSCT) scanner with HR control versus on a dual-source CT (DSCT) scanner without HR control. METHODS. This retrospective study included 509 patients (283 men, 226 women; mean age, 52.1 ± 15.1 [SD] years) at low to intermediate risk for acute coronary syndrome who underwent coronary CTA for acute chest pain during off-hours in a single ED from March 1, 2020, to April 25, 2022. A total of 205 patients initially underwent CTA using a 64-detector-row SSCT scanner with HR control (oral ß-blocker administration if HR was > 65 beats/min); after scanner replacement on April 26, 2021, 304 patients underwent CTA using a third-generation DSCT without HR control. Groups were compared in terms of ED LOS and CT completion time (defined as time from ordering CTA to completion of acquisition) using propensity score matching and additional endpoints including image quality and nondiagnostic examinations based on radiology reports. RESULTS. The DSCT group, compared with the SSCT group, showed no significant difference in median ED LOS (505 vs 457 minutes, respectively; p = .37) but showed shorter median CT completion time (95 vs 117 minutes, p < .001); on the basis of a mediation analysis, 89% of the reduction in CT completion time for DSCT was attributed to the absence of HR control. The DSCT group, compared with the SSCT group, showed higher frequency of examinations with good or excellent image quality (87.8% vs 60.0%, p < .001) and lower frequency of nondiagnostic examinations (1.6% vs 6.3%, p = .01) but showed no significant difference in frequencies of emergent cardiology consultation, invasive angiography, ED disposition, or coronary revascularization (all p > .05). No patient in either group experienced 30-day all-cause mortality or a major adverse cardiovascular event. CONCLUSION. The use of a DSCT scanner for coronary CTA can eliminate the need for ß-blocker administration for HR control while decreasing nondiagnostic examinations. CLINICAL IMPACT. A DSCT scanner can expedite clinical processes in the ED.

Patterns of Postoperative Changes in Lung Volume and Perfusion Assessed by Dual-Energy CT: Comparison of Lobectomy and Limited Resection.

BACKGROUND. Pulmonary function tests (PFTs) and perfusion scintigraphy have limited utility for evaluating postoperative changes in regional pulmonary function after lung cancer resection surgery. OBJECTIVE. The purpose of this study is to compare postoperative changes in lung volume and perfusion, as assessed by dual-energy CT (DECT), between patients undergoing surgical resection of lung cancer by lobectomy versus limited resection as well as to assess associations between such changes and the lobar location of the resected tumor. METHODS. This study entailed a retrospective post hoc analysis of a prospective study that enrolled patients awaiting lung cancer resection surgery between March 2019 and February 2020. Eighty-one patients (38 men and 43 women; mean age, 60.5 ± 8.9 [SD] years), 43 of whom underwent lobectomy and 38 of whom underwent limited resection, were included. Patients underwent thoracic DECT and PFT evaluation preoperatively and at 6 months postoperatively. Pulmonary lobes were segmented. Lobar lung volume and lung perfusion ratios (both relative to whole-lung values) were computed. Perfusion measures reflected DECT-derived iodine content. Patients completed 6-month postoperative quality-of-life (QOL) questionnaires. RESULTS. Patients undergoing lobectomy, compared with those undergoing limited resection, had greater increases in the lung volume ratio of the ipsilateral nonresected lobe(s) (mean, 42.3% ± 24.2% [SD] vs 22.9% ± 13.2%, p < .001) and the contralateral lung (mean, 14.6% ± 14.0% vs 6.4% ± 6.9%, p = .002) as well as greater increases in the lung perfusion ratio of the ipsilateral nonresected lobe(s) (mean, 39.9% ± 20.7% [SD] vs 22.8% ± 17.8%, p < .001) and the contralateral lung (mean, 20.9% ± 9.4% vs 4.3% ± 5.6%, p < .001). In patients with right lower lobe tumors, the largest postoperative increases in the lung volume ratio were in the right middle lobe in those undergoing lobectomy (mean, 44.1% ± 21.0%) and limited resection (mean, 24.6% ± 14.5%), whereas the largest postoperative increase in the lung perfusion ratio was in the left lower lobe in those undergoing lobectomy (mean, 53.9% ± 8.6%) and in the right middle lobe in those undergoing limited resection (mean, 32.5% ± 24.1%). Otherwise, the largest increases in lung volume and perfusion ratios occurred in the ipsilateral nonresected lobes (vs the contra-lateral lobes), regardless of the operative approach used and the lobar location. Changes in the lung volume and perfusion ratios in the ipsilateral lobe(s) and the contralateral lung showed weak correlations with certain QOL scores (e.g., for role functioning: ρ = 0.234-0.279 [volume] and -0.233 to -0.284 [perfusion]). CONCLUSION. DECT depicts patterns of lung volume and perfusion changes after lung cancer surgery, depending on the surgical approach (lobectomy vs limited resection) used and the lobar location of the tumor. CLINICAL IMPACT. DECT-derived metrics can help understand variable physiologic impacts of lung cancer resection surgeries.

Quality assessment of radiomics research in cardiac CT: a systematic review.

OBJECTIVES: To assess the quality of current radiomics research on cardiac CT using radiomics quality score (RQS) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) systems. METHODS: Systematic searches of PubMed and EMBASE were performed to identify all potentially relevant original research articles about cardiac CT radiomics. Fifteen original research articles were selected. Two cardiac radiologists assessed the quality of the methodology adopted in those studies according to the RQS and TRIPOD guidelines. Basic adherence rates for the following six key domains were evaluated: image protocol and reproducibility, feature reduction and validation, biologic/clinical utility, performance index, high level of evidence, and open science. RESULTS: Among the 15 included articles, six (40%) were about coronary artery disease and six (40%) were about myocardial infarction. The mean RQS was 9.9 ± 7.3 (27.4% of the ideal score of 36), and the basic adherence rate was 44.6%. Fourteen (93.3%) and nine (60%) studies performed feature selection and validation, but only two (13.3%) of them performed external validation. Two studies (13.3%) were prospective, and only one study (6.7%) conducted calibration analysis and stated the potential clinical utility. None of the studies conducted phantom study and cost-effective analysis. The overall adherence rate for TRIPOD was 63%. CONCLUSION: The quality of radiomics studies in cardiac CT is currently insufficient. A higher level of evidence is required, and analysis of clinical utility and calibration of model performance need to be improved. KEY POINTS: • The quality of science of radiomics studies in cardiac CT is currently insufficient. • No study conducted a phantom study or cost-effective analysis, with further limitations being demonstrated in a high level of evidence for radiomics studies. • Analysis of clinical utility and calibration of model performance need to be improved, and a higher level of evidence is required.

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.

Feasibility of Aortic Annular Measurements Using Noncontrast-Enhanced Cardiac Computed Tomography in Preprocedural Evaluation of Transcatheter Aortic Valve Replacement: A Comparison With Contrast-Enhanced Computed Tomography.

OBJECTIVE: Noncontrast-enhanced (NCE) cross-sectional images other than contrast-enhanced (CE)-computed tomography (CT) may be necessary for annular sizing before transcatheter aortic valve replacement (TAVR), because of the risk of contrast-induced nephropathy. We aimed to investigate the feasibility of aortic annular measurements using NCE-CT in TAVR candidates by comparing them with CE-CT measurements. METHODS: We retrospectively enrolled 46 patients who underwent CT for the purpose of pre-TAVR evaluation (17 men; mean age, 82.3 ± 5.0 years). On CE and NCE examination, measurements of the average diameter and perimeter of aortic annulus were performed by 2 observers, and coronary ostial heights were measured. Differences in annular parameters and coronary ostial heights between NCE and CE examinations were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs). RESULTS: Aortic annulus measurement values were significantly larger in the NCE examinations compared with those in the CE examinations according to both readers (mean differences of 0.8 mm for the average diameter and 2.1 mm for the perimeter according to observer 1, and 1.1 mm for the average diameter and 3.4 mm for the perimeter according to observer 2; ICC, 0.771-0.923). The mean difference between coronary ostial height measurement on NCE and CE examination was 0.6 mm for left coronary ostium (ICC, 0.795) and 0.7 mm for right coronary ostium (ICC, 0.802). No case showed disagreement between NCE and CE examinations for hypothetical valve sizing. CONCLUSIONS: Noncontrast-enhanced cardiac CT examination may be feasible for aortic annular measurements before TAVR and provides comparable measurement values to CE examination.

Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4+ and CD8+ T Cells through NF-κB p65 Signaling Pathway in Mice.

Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.

Hepatocyte-Specific Deficiency of DAX-1 Protects Mice from Acetaminophen-Induced Hepatotoxicity by Activating NRF2 Signaling.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.

Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis.

Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 µg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by Woodard in this issue.

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.

Prevalence of abnormal cardiovascular magnetic resonance findings in recovered patients from COVID-19: a systematic review and meta-analysis.

BACKGROUND: The prevalence of abnormal cardiovascular magnetic resonance (CMR) findings in recovered coronavirus disease 2019 (COVID-19) patients is unclear. This study aimed to investigate the prevalence of abnormal CMR findings in recovered COVID-19 patients. METHODS: A systematic literature search was performed to identify studies that report the prevalence of abnormal CMR findings in recovered COVID-19 patients. The number of patients with abnormal CMR findings and diagnosis of myocarditis on CMR (based on the Lake Louise criteria) and each abnormal CMR parameter were extracted. Subgroup analyses were performed according to patient characteristics (athletes vs. non-athletes and normal vs. undetermined cardiac enzyme levels). The pooled prevalence and 95% confidence interval (CI) of each CMR finding were calculated. Study heterogeneity was assessed, and meta-regression analysis was performed to investigate factors associated with heterogeneity. RESULTS: In total, 890 patients from 16 studies were included in the analysis. The pooled prevalence of one or more abnormal CMR findings in recovered COVID-19 patients was 46.4% (95% CI 43.2%-49.7%). The pooled prevalence of myocarditis and late gadolinium enhancement (LGE) was 14.0% (95% CI 11.6%-16.8%) and 20.5% (95% CI 17.7%-23.6%), respectively. Further, heterogeneity was observed (I2 > 50%, p < 0.1). In the subgroup analysis, the pooled prevalence of abnormal CMR findings and myocarditis was higher in non-athletes than in athletes (62.5% vs. 17.1% and 23.9% vs. 2.5%, respectively). Similarly, the pooled prevalence of abnormal CMR findings and LGE was higher in the undetermined than in the normal cardiac enzyme level subgroup (59.4% vs. 35.9% and 45.5% vs. 8.3%, respectively). Being an athlete was a significant independent factor related to heterogeneity in multivariate meta-regression analysis (p < 0.05). CONCLUSIONS: Nearly half of recovered COVID-19 patients exhibited one or more abnormal CMR findings. Athletes and patients with normal cardiac enzyme levels showed a lower prevalence of abnormal CMR findings than non-athletes and patients with undetermined cardiac enzyme levels. Trial registration The study protocol was registered in the PROSPERO database (registration number: CRD42020225234).

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.

Usefulness of cardiac magnetic resonance images for prediction of sudden cardiac arrest in patients with mitral valve prolapse: a multicenter retrospective cohort study.

BACKGROUND: An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. METHODS: MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. RESULTS: Of the 85 patients [age, 54.0 (41.0-65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65-148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02-1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08-1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. CONCLUSIONS: The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

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.