Synthetic hematocrit from virtual non-contrast images for myocardial extracellular volume evaluation with photon-counting detector CT.

OBJECTIVES: To assess the accuracy of a synthetic hematocrit derived from virtual non-contrast (VNC) and virtual non-iodine images (VNI) for myocardial extracellular volume (ECV) computation with photon-counting detector computed tomography (PCD-CT). MATERIALS AND METHODS: Consecutive patients undergoing PCD-CT including a coronary CT angiography (CCTA) and a late enhancement (LE) scan and having a blood hematocrit were retrospectively included. In the first 75 patients (derivation cohort), CCTA and LE scans were reconstructed as VNI at 60, 70, and 80 keV and as VNC with quantum iterative reconstruction (QIR) strengths 2, 3, and 4. Blood pool attenuation (BPmean) was correlated to blood hematocrit. In the next 50 patients (validation cohort), synthetic hematocrit was calculated using BPmean. Myocardial ECV was computed using the synthetic hematocrit and compared with the ECV using the blood hematocrit as a reference. RESULTS: In the derivation cohort (49 men, mean age 79 ± 8 years), a correlation between BPmean and blood hematocrit ranged from poor for VNI of CCTA at 80 keV, QIR2 (R2 = 0.12) to moderate for VNI of LE at 60 keV, QIR4; 70 keV, QIR3 and 4; and VNC of LE, QIR3 and 4 (all, R2 = 0.58). In the validation cohort (29 men, age 75 ± 14 years), synthetic hematocrit was calculated from VNC of the LE scan, QIR3. Median ECV was 26.9% (interquartile range (IQR), 25.5%, 28.8%) using the blood hematocrit and 26.8% (IQR, 25.4%, 29.7%) using synthetic hematocrit (VNC, QIR3; mean difference, -0.2%; limits of agreement, -2.4%, 2.0%; p = 0.33). CONCLUSION: Synthetic hematocrit calculated from VNC images enables an accurate computation of myocardial ECV with PCD-CT. CLINICAL RELEVANCE STATEMENT: Virtual non-contrast images from cardiac late enhancement scans with photon-counting detector CT allow the calculation of a synthetic hematocrit, which enables accurate computation of myocardial extracellular volume. KEY POINTS: Blood hematocrit is mandatory for conventional myocardial extracellular volume computation. Synthetic hematocrit can be calculated from virtual non-iodine and non-contrast photon-counting detector CT images. Synthetic hematocrit from virtual non-contrast images enables computation of the myocardial extracellular volume.

Comparative analysis of late gadolinium enhancement assessment techniques for monitoring fibrotic changes in myocarditis follow-up.

OBJECTIVES: To compare the repeatability and interrelation of various late gadolinium enhancement (LGE) assessment techniques for monitoring fibrotic changes in myocarditis follow-up. MATERIALS AND METHODS: LGE extent change between baseline and 3-month cardiovascular magnetic resonance (CMR) was compared in patients with acute myocarditis using the full width at half maximum (FWHM), gray-scale thresholds at 5 and 6 standard deviations (SD5 and SD6), visual assessment with threshold (VAT) and full manual (FM) techniques. In addition, visual presence score (VPS), visual transmurality score (VTS), and a simplified visual change score (VCS) were assessed. Intraclass-correlation (ICC) was used to evaluate repeatability, and methods were compared using Spearman's correlation. RESULTS: Forty-seven patients (38 male, median age: 27 [IQR: 21; 38] years) were included. LGE extent change differed among quantitative techniques (p < 0.01), with variability in the proportion of patients showing LGE change during follow-up (FWHM: 62%, SD5: 74%, SD6: 66%, VAT: 43%, FM: 60%, VPS: 53%, VTS: 77%, VCS: 89%). Repeatability was highest with FWHM (ICC: 0.97) and lowest with SD5 (ICC: 0.89). Semiquantitative scoring had slightly lower values (VPS ICC: 0.81; VTS ICC: 0.71). VCS repeatability was excellent (ICC: 0.93). VPS and VTS correlated with quantitative techniques, while VCS was positively associated with VPS, VTS, VAT, and FM, but not with FWHM, SD5, and SD6. CONCLUSION: FWHM offers the least observer-dependent LGE follow-up after myocarditis. VPS, VTS, and VCS are practical alternatives, showing reliable correlations with quantitative methods. Classification of patients exhibiting either stable or changing LGE relies on the assessment technique. CLINICAL RELEVANCE STATEMENT: This study shows that LGE monitoring in myocarditis is technique-dependent; the FWHM method yields the most consistent fibrotic tracking results, with scoring-based techniques as reliable alternatives. KEY POINTS: Recognition of fibrotic changes during myocarditis follow-up is significantly influenced by the choice of the quantification technique employed. The FWHM technique ensures highly repeatable tracking of myocarditis-related LGE changes. Segment-based visual scoring and the simplified visual change score offer practical, reproducible alternatives in resource-limited settings.

Impact of late gadolinium enhancement image acquisition resolution on neural network based automatic scar segmentation.

BACKGROUND: Automatic myocardial scar segmentation from late gadolinium enhancement (LGE) images using neural networks promises an alternative to time-consuming and observer-dependent semi-automatic approaches. However, alterations in data acquisition, reconstruction as well as post-processing may compromise network performance. The objective of the present work was to systematically assess network performance degradation due to a mismatch of point-spread function between training and testing data. METHODS: Thirty-six high-resolution (0.7×0.7×2.0 mm3) LGE k-space datasets were acquired post-mortem in porcine models of myocardial infarction. The in-plane point-spread function and hence in-plane resolution Δx was retrospectively degraded using k-space lowpass filtering, while field-of-view and matrix size were kept constant. Manual segmentation of the left ventricle (LV) and healthy remote myocardium was performed to quantify location and area (% of myocardium) of scar by thresholding (≥ SD5 above remote). Three standard U-Nets were trained on training resolutions Δxtrain = 0.7, 1.2 and 1.7 mm to predict endo- and epicardial borders of LV myocardium and scar. The scar prediction of the three networks for varying test resolutions (Δxtest = 0.7 to 1.7 mm) was compared against the reference SD5 thresholding at 0.7 mm. Finally, a fourth network trained on a combination of resolutions (Δxtrain = 0.7 to 1.7 mm) was tested. RESULTS: The prediction of relative scar areas showed the highest precision when the resolution of the test data was identical to or close to the resolution used during training. The median fractional scar errors and precisions (IQR) from networks trained and tested on the same resolution were 0.0 percentage points (p.p.) (1.24 - 1.45), and - 0.5 - 0.0 p.p. (2.00 - 3.25) for networks trained and tested on the most differing resolutions, respectively. Deploying the network trained on multiple resolutions resulted in reduced resolution dependency with median scar errors and IQRs of 0.0 p.p. (1.24 - 1.69) for all investigated test resolutions. CONCLUSION: A mismatch of the imaging point-spread function between training and test data can lead to degradation of scar segmentation when using current U-Net architectures as demonstrated on LGE porcine myocardial infarction data. Training networks on multi-resolution data can alleviate the resolution dependency.

Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes.

BACKGROUND AND AIMS: Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS). METHODS: Plasma cDPP3 levels were assessed at baseline and 12-24 h after presentation in patients with ACS prospectively enrolled into the multi-centre SPUM-ACS study (n = 4787). RESULTS: Circulating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score [per log-2 increase, hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.05-1.82, P = .021]. High cDPP3 was an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36-2.58, P < .001) and at one year (HR 1.61, 95% CI 1.28-2.02, P < .001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12-24 h were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86-37.09, P < .001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70-12.42, P < .001). Results were consistent across various patient subgroups. CONCLUSIONS: This study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment.

Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T.

BACKGROUND: Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs). METHODS: We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT-Elecsys) and 3 hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD. RESULTS: Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all P<0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7-32.5 ng/L] versus 5 ng/L [IQR, 3-9 ng/L]; P<0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI-Architect, 2.5 ng/L [IQR, 1.2-6.2 ng/L] versus 2.9 ng/L [IQR, 1.8-5.0 ng/L]; hs-cTnI-Access, 3.3 ng/L [IQR, 2.4-6.1 ng/L] versus 2.7 ng/L [IQR, 1.6-5.0 ng/L]; and hs-cTnI-Vista, 7.4 ng/L [IQR, 5.2-13.4 ng/L] versus 7.5 ng/L [IQR, 6-10 ng/L]). hs-cTnT-Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects (P<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2, encoding cTnT (but none for TNNI3, encoding cTnI) versus control subjects (n=16, PWald<0.001); the expression correlated with pathological disease activity (R=0.59, Pt-statistic<0.001) and circulating hs-cTnT concentrations (R=0.26, Pt-statistic=0.031). CONCLUSIONS: In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03660969.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study.

PURPOSE: Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS: Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS: Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min-1*g-1 [IQR 2.18-3.08] vs. 2.20 mL*min-1*g-1 [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION: In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement.

Diagnostic performance of 3D cardiac magnetic resonance perfusion in elderly patients for the detection of coronary artery disease as compared to fractional flow reserve.

OBJECTIVES: In patients of advanced age, the feasibility of myocardial ischemia testing might be limited by age-related comorbidities and falling compliance abilities. Therefore, we aimed to test the accuracy of 3D cardiac magnetic resonance (CMR) stress perfusion in the elderly population as compared to reference standard fractional flow reserve (FFR). METHODS: Fifty-six patients at age 75 years or older (mean age 79 ± 4 years, 35 male) underwent 3D CMR perfusion imaging and invasive coronary angiography with FFR in 5 centers using the same study protocol. The diagnostic accuracy of CMR was compared to a control group of 360 patients aged below 75 years (mean age 61 ± 9 years, 262 male). The percentage of myocardial ischemic burden (MIB) relative to myocardial scar burden was further analyzed using semi-automated software. RESULTS: Sensitivity, specificity, and positive and negative predictive values of 3D perfusion CMR deemed similar for both age groups in the detection of hemodynamically relevant (FFR < 0.8) stenosis (≥ 75 years: 86%, 83%, 92%, and 75%; < 75 years: 87%, 80%, 82%, and 85%; p > 0.05 all). While MIB was larger in the elderly patients (15% ± 17% vs. 9% ± 13%), the diagnostic accuracy of 3D CMR perfusion was high in both elderly and non-elderly populations to predict pathological FFR (AUC: 0.906 and 0.866). CONCLUSIONS: 3D CMR perfusion has excellent diagnostic accuracy for the detection of hemodynamically relevant coronary stenosis, independent of patient age. KEY POINTS: • The increasing prevalence of coronary artery disease in elderly populations is accompanied with a larger ischemic burden of the myocardium as compared to younger individuals. • 3D cardiac magnetic resonance perfusion imaging predicts pathological fractional flow reserve in elderly patients aged ≥ 75 years with high diagnostic accuracy. • Ischemia testing with 3D CMR perfusion imaging has similarly high accuracy in the elderly as in younger patients and it might be particularly useful when other non-invasive techniques are limited by aging-related comorbidities and falling compliance abilities.

Novel plasma biomarkers predicting biventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular involvement in ARVC may lead to heart failure. This study aimed to investigate the role of plasma biomarkers soluble (s)ST2, Galectin-3 (Gal-3) and GDF-15 in predicting biventricular involvement and adverse outcomes in ARVC. METHODS AND RESULTS: ARVC patients from 2 independent cohorts, were studied. The Bejing (Chinese) cohort (n = 108) was the discovery cohort, whereas the Zurich (Swiss) cohort (n = 47) served as validation. All patients had a definite ARVC diagnosis at time of blood withdrawal. Biomarkers were independently correlated with NT-proBNP and left ventricular (LV)-function. ARVC patients with LV involvement had higher levels of sST2 and GDF-15 as compared to controls and patients with isolated right ventricle (RV) involvement. sST2 and GDF-15 were significantly correlated with late gadolinium enhancement in CMR and with adverse heart failure outcomes. Gal-3 was elevated in ARVC patients with and without LV involvement. The combined use of the three biomarkers (sST2, GDF-15 and NT-proBNP) showed the best performance in predicting LV involvement in both cohorts. Plasma drawn from the coronary arteries and coronary sinus indicated a transmyocardial elevation of sST2, but no transmyocardial gradient of GDF-15. After heart transplantation, both sST2 and GDF-15 returned to near-normal levels. CONCLUSION: Our study showed that sST2 and GDF-15 may predict biventricular involvement in ARVC. The combined use of sST2, GDF-15 and NT-proBNP showed the best prediction of biventricular involvement in ARVC.

Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg every day; days 4 and 5: 5.0 mg every day) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 hours to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION: The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

Free-breathing motion-informed locally low-rank quantitative 3D myocardial perfusion imaging.

PURPOSE: To propose respiratory motion-informed locally low-rank reconstruction (MI-LLR) for robust free-breathing single-bolus quantitative 3D myocardial perfusion CMR imaging. Simulation and in-vivo results are compared to locally low-rank (LLR) and compressed sensing reconstructions (CS) for reference. METHODS: Data were acquired using a 3D Cartesian pseudo-spiral in-out k-t undersampling scheme (R = 10) and reconstructed using MI-LLR, which encompasses two stages. In the first stage, approximate displacement fields are derived from an initial LLR reconstruction to feed a motion-compensated reference system to a second reconstruction stage, which reduces the rank of the inverse problem. For comparison, data were also reconstructed with LLR and frame-by-frame CS using wavelets as sparsifying transform ( ℓ1$$ {\ell}_1 $$ -wavelet). Reconstruction accuracy relative to ground truth was assessed using synthetic data for realistic ranges of breathing motion, heart rates, and SNRs. In-vivo experiments were conducted in healthy subjects at rest and during adenosine stress. Myocardial blood flow (MBF) maps were derived using a Fermi model. RESULTS: Improved uniformity of MBF maps with reduced local variations was achieved with MI-LLR. For rest and stress, intra-volunteer variation of absolute and relative MBF was lower in MI-LLR (±0.17 mL/g/min [26%] and ±1.07 mL/g/min [33%]) versus LLR (±0.19 mL/g/min [28%] and ±1.22 mL/g/min [36%]) and versus ℓ1$$ {\ell}_1 $$ -wavelet (±1.17 mL/g/min [113%] and ±6.87 mL/g/min [115%]). At rest, intra-subject MBF variation was reduced significantly with MI-LLR. CONCLUSION: The combination of pseudo-spiral Cartesian undersampling and dual-stage MI-LLR reconstruction improves free-breathing quantitative 3D myocardial perfusion CMR imaging under rest and stress condition.

Diagnosis of acute heart failure in CT pulmonary angiography: feasibility and accuracy.

OBJECTIVES: To evaluate the feasibility and accuracy of diagnosing acute heart failure (HF) with CT pulmonary angiography (CTPA) in emergency department patients. METHODS: In this retrospective single-center study, we evaluated 150 emergency department patients (mean age 65 ± 17 years) undergoing CTPA with a fixed scan (100 kVp) and contrast media protocol (60 mL, 4 mL/s) who had no pulmonary embolism (PE). Patients were subdivided into training cohort (n = 100) and test cohort (n = 50). Three independent, blinded readers measured the attenuation in the right ventricle (RV) and left ventricle (LV) on axial images. The ratio (HUratio) and difference (HUdiff) between RV and LV attenuation were calculated. Diagnosis of acute HF was made on the basis of clinical, laboratory, and echocardiography data. Optimal thresholds, sensitivity, and specificity were calculated using the area under the curve (AUC) from receiver operating characteristics analysis. RESULTS: Fifty-nine of the 150 patients (40%) were diagnosed with acute HF. Attenuation measurements showed an almost perfect interobserver agreement (intraclass correlation coefficient: 0.986, 95%CI: 0.980-0.991). NT-pro BNP exhibited moderate correlations with HUratio (r = 0.50, p < 0.001) and HUdiff (r = 0.50, p < 0.001). In the training cohort, HUratio (AUC: 0.89, 95%CI: 0.82-0.95) and HUdiff (AUC: 0.88, 95%CI: 0.81-0.95) showed a very good performance to diagnose HF. Optimal cutoff values were 1.42 for HUratio (sensitivity 93%; specificity 75%) and 113 for HUdiff (sensitivity 93%; specificity 73%). Applying these thresholds to the test cohort yielded a sensitivity of 89% and 89% and a specificity of 69% and 63% for HUratio and HUdiff, respectively. CONCLUSION: In emergency department patients undergoing CTPA and showing no PE, both HUratio and HUdiff have a high sensitivity for diagnosing acute HF. KEY POINTS: • Heart failure is a common differential diagnosis in patients undergoing CT pulmonary angiography. • In emergency department patients undergoing CT pulmonary angiography and showing no pulmonary embolism, attenuation differences of the left and right ventricle have a high sensitivity for diagnosing acute heart failure.

Epicardial Adipose Tissue Attenuation and Fat Attenuation Index: Phantom Study and In Vivo Measurements With Photon-Counting Detector CT.

BACKGROUND. Epicardial adipose tissue (EAT) attenuation is a vascular inflammation marker predictive of adverse cardiac events. The fat attenuation index (FAI) assesses fat attenuation for predefined coronary segments. Photon-counting detector (PCD) CT uses routine virtual monoenergetic image (VMI) reconstructions. VMI energy level may affect EAT attenuation and FAI measurements. OBJECTIVE. The purpose of this article was to assess EAT attenuation and FAI measurements at different monoenergetic energy levels in patients undergoing coronary CTA using a first-generation whole-body dual-source PCD CT scanner. METHODS. An anthropomorphic phantom at two sizes with a fat insert was imaged on a first-generation dual-source PCD CT scanner and, as a reference, on a conventional energy-integrating detector (EID) CT scanner at 120 kV. Thirty patients (11 women, 19 men; mean age, 48 ± 10 years; Agatston score < 60) who underwent an ECG-gated unenhanced calcium-scoring scan and contrast-enhanced coronary CTA by PCD CT were retrospectively evaluated. VMIs from 55 to 80 keV at 5-keV increments were reconstructed. EAT attenuation was manually measured on unenhanced and contrast-enhanced images. FAI was calculated using semiautomated software. RESULTS. The attenuation of the phantom fat insert was -69 HU for the reference EID CT; the closest attenuation for PCD CT was observed at 70 keV for the small (-69 HU) and large (-70 HU) phantoms. In patients, EAT attenuation increased for unenhanced acquisition from -111 ± 11 HU at 55 keV to -82 ± 9 HU at 80 keV and for contrast-enhanced acquisition from -104 ± 11 HU at 55 keV to -81 ± 9 HU at 80 keV. The mean attenuation difference between unenhanced and contrast-enhanced scans decreased with increasing energy level (from 7 ± 12 HU to 1 ± 10 HU). The FAI increased from -89 ± 8 HU at 55 keV to -77 ± 12 HU at 80 keV for the right coronary artery, -95 ± 11 HU at 55 keV to -85 ± 11 HU at 80 keV for the left anterior descending artery, and -87 ± 10 HU at 55 keV to -80 ± 12 HU at 80 keV for the circumflex artery. CONCLUSION. EAT attenuation and FAI measurements using PCD CT are impacted by VMI energy level and contrast enhancement. Use of VMI reconstruction at 70 keV provides fat attenuation approximating conventional polychromatic measurements. CLINICAL IMPACT. The findings may help standardize evaluation of pericoronary inflammation by PCD CT as a measure of patients' cardiac risk.

Segmental strain for scar detection in acute myocardial infarcts and in follow-up exams using non-contrast CMR cine sequences.

BACKGROUND: The purpose of the study was to investigate feasibility of infarct detection in segmental strain derived from non-contrast cardiac magnetic resonance (CMR) cine sequences in patients with acute myocardial infarction (AMI) and in follow-up (FU) exams. METHODS: 57 patients with AMI (mean age 61 ± 12 years, CMR 2.8 ± 2 days after infarction) were retrospectively included, FU exams were available in 32 patients (35 ± 14 days after first CMR). 43 patients with normal CMR (54 ± 11 years) served as controls. Dedicated software (Segment CMR, Medviso) was used to calculate global and segmental strain derived from cine sequences. Cine short axis stacks and segmental circumferential strain calculations of every patient and control were presented to two blinded readers in random order, who were advised to identify potentially infarcted segments, blinded to LGE and clinical information. RESULTS: Impaired global strain was measured in AMI patients compared to controls (global peak circumferential strain [GPCS] p = 0.01; global peak longitudinal strain [GPLS] p = 0.04; global peak radial strain [GPRS] p = 0.01). In both imaging time points, mean segmental peak circumferential strain [SPCS] was impaired in infarcted tissue compared to remote segments (AMI: p = 0.03, FU: p = 0.02). SPCS values in infarcted segments were similar between AMI and FU (p = 0.8). In SPCS calculations, 141 from 189 acutely infarcted segments were accurately detected (74.6%), visual evaluation of correlating cine images detected 43.4% infarcts. In FU, 80% infarcted segments (91/114 segments) were detected in SPCS and 51.8% by visual evaluation of correlating short axis cine images (p = 0.01). CONCLUSION: Segmental circumferential strain derived from routinely acquired native cine sequences detects nearly 75% of acute infarcts and 80% of infarcts in subacute follow-up CMR, significantly more than visual evaluation of correlating cine images alone. Acute infarcts may display only subtle impairment of wall motion and no obvious wall thinning, thus SPCS calculation might be helpful for scar detection in patients with acute infarcts, when LGE images are not available.

Cholinergic and dopaminergic effects on prediction error and uncertainty responses during sensory associative learning.

Navigating the physical world requires learning probabilistic associations between sensory events and their change in time (volatility). Bayesian accounts of this learning process rest on hierarchical prediction errors (PEs) that are weighted by estimates of uncertainty (or its inverse, precision). In a previous fMRI study we found that low-level precision-weighted PEs about visual outcomes (that update beliefs about associations) activated the putative dopaminergic midbrain; by contrast, precision-weighted PEs about cue-outcome associations (that update beliefs about volatility) activated the cholinergic basal forebrain. These findings suggested selective dopaminergic and cholinergic influences on precision-weighted PEs at different hierarchical levels. Here, we tested this hypothesis, repeating our fMRI study under pharmacological manipulations in healthy participants. Specifically, we performed two pharmacological fMRI studies with a between-subject double-blind placebo-controlled design: study 1 used antagonists of dopaminergic (amisulpride) and muscarinic (biperiden) receptors, study 2 used enhancing drugs of dopaminergic (levodopa) and cholinergic (galantamine) modulation. Pooled across all pharmacological conditions of study 1 and study 2, respectively, we found that low-level precision-weighted PEs activated the midbrain and high-level precision-weighted PEs the basal forebrain as in our previous study. However, we found pharmacological effects on brain activity associated with these computational quantities only when splitting the precision-weighted PEs into their PE and precision components: in a brainstem region putatively containing cholinergic (pedunculopontine and laterodorsal tegmental) nuclei, biperiden (compared to placebo) enhanced low-level PE responses and attenuated high-level PE activity, while amisulpride reduced high-level PE responses. Additionally, in the putative dopaminergic midbrain, galantamine compared to placebo enhanced low-level PE responses (in a body-weight dependent manner) and amisulpride enhanced high-level precision activity. Task behaviour was not affected by any of the drugs. These results do not support our hypothesis of a clear-cut dichotomy between different hierarchical inference levels and neurotransmitter systems, but suggest a more complex interaction between these neuromodulatory systems and hierarchical Bayesian quantities. However, our present results may have been affected by confounds inherent to pharmacological fMRI. We discuss these confounds and outline improved experimental tests for the future.

Incremental Prognostic Value of Coronary Artery Calcium Score for Predicting All-Cause Mortality after Transcatheter Aortic Valve Replacement.

Background Current risk models show limited performances for predicting all-cause mortality after transcatheter aortic valve replacement (TAVR). Purpose To determine the prognostic value of coronary artery calcium (CAC) scoring for predicting 30-day and 1-year mortality in patients undergoing TAVR. Materials and Methods In this single-center institutional review board-approved secondary analysis of prospectively collected data (SwissTAVI Registry), the authors evaluated participants who, before TAVR, underwent CT that included a nonenhanced electrocardiography-gated cardiac scan between May 2008 and September 2019 and who had not undergone previous coronary revascularization. Clinical data, including the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), were recorded. The CAC score was determined, and 30-day and 1-year all-cause mortality were assessed by using Cox regression analyses. Results In total, 309 participants (mean age ± standard deviation, 81 years ± 7; 175 women) were included, with a median CAC score of 334 (interquartile range, 104-987). Seventy-seven of the 309 participants (25%) had a CAC score greater than or equal to 1000. A CAC score of 1000 or greater served as an independent predictor of 30-day (hazard ratio [HR], 4.5 [95% CI: 1.5, 13.6] compared with a CAC score <1000; P = .007) and 1-year (HR, 4.3 [95% CI: 1.5, 12.7] compared with a CAC score of 0-99; P = .008) mortality after TAVR. Similar trends were observed for each point increase of the EuroSCORE II as an independent predictor of 30-day (HR, 1.22 [95% CI: 1.10, 1.36]; P < .001) and 1-year (HR, 1.16 [95% CI: 1.08, 1.25]; P < .001) mortality. Adding the CAC score to the EuroSCORE II provided incremental prognostic value for 1-year mortality after TAVR over the EuroSCORE II alone (concordance index, 0.76 vs 0.69; P = .04). Conclusion In participants without prior coronary revascularization, the coronary artery calcium score represented an independent predictor of 30-day and 1-year mortality after transcatheter aortic valve replacement. ClinicalTrials.gov identifier, NCT01368250 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

[Non-invasive Imaging of Chronic Coronary Syndromes - CT Coronary Angiography and Stress Perfusion Cardiac MRI]. / Nicht-invasive Diagnostik der chronischen koronaren Herzkrankheit ­ CT-Koronarangio­graphie und Stress-MRT.

Non-invasive Imaging of Chronic Coronary Syndromes - CT Coronary Angiography and Stress Perfusion Cardiac MRI Abstract. Coronary artery disease (CAD) is amongst the leading causes of death worldwide. The European Society of Cardiology (ESC) has recently published new guidelines on diagnosis and management of chronic coronary syndromes. These guidelines emphasize the use of non-invasive imaging tests to assess CAD. Compared to previous versions of these guidelines, the pre-test probabilities of CAD based on age, sex and symptoms have been adjusted downward. Unless obstructive CAD can be excluded by clinical assessment alone, various strategies to diagnose CAD in symptomatic patients may be used: coronary CT angiography, non-invasive functional imaging for myocardial ischaemia, or invasive coronary angiography combined with functional evaluation. This review summarizes strengths and weaknesses of non-invasive cardiac imaging modalities with emphasize on coronary CT angiography and stress perfusion cardiac magnetic resonance (CMR) imaging.

Retrospective phase-based gating for cardiac proton spectroscopy with fixed scan time.

BACKGROUND: Respiratory motion is a major limiting factor for spectral quality and duration of in vivo proton MR spectroscopy of the heart. Prospective navigator gating is frequently applied to minimize the effects of respiratory motion, but scan durations are subject-dependent and hence difficult to predict. PURPOSE: To implement cardiac proton MRS with fixed scan time by employing retrospective phase-based gating and to compare the proposed method to conventional navigator-gated MRS. STUDY TYPE: Prospective. SUBJECTS: Eighteen healthy volunteers (29.7 ± 7.8 years). FIELD STRENGTH/SEQUENCE: 1.5, navigator-gated (16 averages without, 96 with water suppression [WS]) data acquisition as reference and navigator-free data acquisition with a fixed scan time (48 without WS, 304 with WS), cardiac-triggered point-resolved spectroscopy (PRESS). ASSESSMENT: Navigator-free data acquisition with retrospective phase-based gating was compared with prospective navigator-gating. Navigator-free acquisition was repeated in 10 subjects to assess reproducibility. Scan time was assessed for prospective and retrospective gating. Retrospective phase-based gating was performed using a threshold based on the standard deviation (SD) of individual water (W) and triglyceride (TG) phases. STATISTICAL TESTS: T-tests and Bland-Altman analysis. RESULTS: The duration of the prospective navigator-gated scans ranged from 6:09 minutes to 21:50 minutes (mean 10:05 ± 3:46 min, gating efficiency 40.4 ± 10.5%), while data acquisition for retrospective phase-based gating had a fixed scan time of 11:44 minutes. Retrospective phase-based gating using a threshold of 1 × SD yielded a gating efficiency of 72.7 ± 4.3% and a coefficient of variation (CoV) of triglyceride-to-water ratios of 9.8% compared with the navigated reference. The intrasubject reproducibility of retrospective gating revealed a CoV of 9.5%. DATA CONCLUSION: Cardiac proton MRS employing retrospective phase-based gating is feasible and provides reproducible assessment of TG/W in a fixed scan time. Since scan time is independent of respiratory motion, retrospective phase-based gating offers an approach to motion compensation with predictable exam time for proton MRS of the heart. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1973-1981.

Characterizing cardiac involvement in amyloidosis using cardiovascular magnetic resonance diffusion tensor imaging.

BACKGROUND: In-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls. METHODS: Ten patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A). RESULTS: MD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10- 3 vs 1.41 ± 0.07 10- 3 mm2/s, p <  0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p <  0.001). MD demonstrated an excellent correlation with native T1 (r = 0.908, p <  0.001) while FA showed a significant correlation with ECV in the CA population (r = - 0.851, p <  0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain (r = 0.921, p < 0.001). CONCLUSION: CMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA.

Myocardial triglycerides in cardiac amyloidosis assessed by proton cardiovascular magnetic resonance spectroscopy.

BACKGROUND: Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis. METHODS: 1H-CMRS was performed on a 1.5 T system (Achieva, Philips Healthcare, Best, The Netherlands) using a 5-channel receive coil in 11 patients with cardiac amyloidosis (60.5 ± 11.4 years, 8 males) and 11 age- and gender-matched controls (63.2 ± 8.9 years, 8 males). After cardiac morphology and function assessment, proton spectra from the interventricular septum (IVS) were acquired using a double-triggered PRESS sequence. Post-processing was performed using a customized reconstruction pipeline based on ReconFrame (GyroTools LLC, Zurich, Switzerland). Spectra were fitted in jMRUI/AMARES and the ratios of triglyceride-to-water (TG/W) and total creatine-to-water (CR/W) were calculated. RESULTS: Besides an increased LV mass and a thickened IVS concomitant to the disease characteristics, patients with cardiac amyloidosis presented with decreased global longitudinal (GLS) and circumferential (GCS) strain. LV ejection fraction was preserved relative to controls (60.0 ± 13.2 vs. 66.1 ± 4.3%, p = 0.17). Myocardial TG/W ratios were significantly decreased compared to controls (0.53 ± 0.23 vs. 0.80 ± 0.26%, p = 0.015). CR/W ratios did not show a difference between both groups, but a higher standard deviation in patients with cardiac amyloidosis was observed. Pearson correlation revealed a negative association between elevated LV mass and TG/W (R = - 0.59, p = 0.004) as well as GCS (R = - 0.48, p = 0.025). CONCLUSIONS: A decrease in myocardial TG/W can be detected in patients with cardiac amyloidosis alongside impaired cardiac function with an association to the degree of myocardial thickening. Accordingly, 1H-CMRS may provide an additional diagnostic tool to gauge progression of cardiac amyloidosis along with standard imaging sequences. TRIAL REGISTRATION: EK 2013-0132.

Cardiac- versus diaphragm-based respiratory navigation for proton spectroscopy of the heart.

OBJECTIVES: To study inter-individual differences of the relation between diaphragm and heart motion, the objective of the present study was to implement respiratory navigation on the heart and compare it against the established method of navigator gating on the diaphragm for single-voxel cardiac 1H-MRS. MATERIALS AND METHODS: 1H-MRS was performed on a 1.5T system in 19 healthy volunteers of mixed age (range 24-75 years). Spectra were recorded in a 6-8 ml voxel in the ventricular septum using a PRESS (point-resolved spectroscopy) sequence and ECG gating. Water-unsuppressed data acquired with pencil beam navigation on the heart were compared to data with navigation on the diaphragm. Water-suppressed data were obtained to assess triglyceride-to-water ratios. RESULTS: Water phase and amplitude fluctuations for cardiac versus diaphragm navigation did not reveal significant differences. Both navigator positions provided comparable triglyceride-to-water ratios and gating efficiencies (coefficient of variation (CoV) 7.0%). The cardiac navigator showed a good reproducibility (CoV 5.2%). DISCUSSION: Respiratory navigation on the heart does not convey an advantage over diaphragm-based navigator gating for cardiac 1H-MRS, but also no disadvantage. Consequently, cardiac and diaphragm respiratory navigation may be used interchangeably.