Tomoelastography and Pancreatic Extracellular Volume Fraction Derived From MRI for Predicting Clinically Relevant Postoperative Pancreatic Fistula.

BACKGROUND: Pancreatic stiffness and extracellular volume fraction (ECV) are potential imaging biomarkers for pancreatic fibrosis. Clinically relevant postoperative fistula (CR-POPF) is one of the most severe complications after pancreaticoduodenectomy. Which imaging biomarker performs better for predicting the risk of CR-POPF remains unknown. PURPOSE: To evaluate the diagnostic performance of ECV and tomoelastography-derived pancreatic stiffness for predicting the risk of CR-POPF in patients undergoing pancreaticoduodenectomy. STUDY TYPE: Prospective. POPULATION: Eighty patients who underwent multiparametric pancreatic MRI before pancreaticoduodenectomy, among whom 16 developed CR-POPF and 64 did not. FIELD STRENGTH/SEQUENCE: 3 T/tomoelastography and precontrast and postcontrast T1 mapping of the pancreas. ASSESSMENT: Pancreatic stiffness was measured on the tomographic c-map, and pancreatic ECV was calculated from precontrast and postcontrast T1 maps. Pancreatic stiffness and ECV were compared with histological fibrosis grading (F0-F3). The optimal cutoff values for predicting CR-POPF were determined, and the correlation between CR-POPF and imaging parameters was evaluated. STATISTICAL TESTS: The Spearman's rank correlation and multivariate linear regression analysis was conducted. The receiver operating characteristic curve analysis and logistic regression analysis was performed. A double-sided P < 0.05 indicated a statistically significant difference. RESULTS: Pancreatic stiffness and ECV both showed a significantly positive correlation with histological pancreatic fibrosis (r = 0.73 and 0.56, respectively). Patients with advanced pancreatic fibrosis had significantly higher pancreatic stiffness and ECV compared to those with no/mild fibrosis. Pancreatic stiffness and ECV were also correlated with each other (r = 0.58). Lower pancreatic stiffness (<1.38 m/sec), lower ECV (<0.28), nondilated main pancreatic duct (<3 mm) and pathological diagnosis other than pancreatic ductal adenocarcinoma were associated with higher risk of CR-POPF at univariate analysis, and pancreatic stiffness was independently associated with CR-POPF at multivariate analysis (odds ratio: 18.59, 95% confidence interval: 4.45, 77.69). DATA CONCLUSION: Pancreatic stiffness and ECV were associated with histological fibrosis grading, and pancreatic stiffness was an independent predictor for CR-POPF. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 5.

Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored. AIMS: We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR. METHODS: One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues. RESULTS: Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008). CONCLUSION: The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker.

Extracellular Volume Fraction by Computed Tomography Predicts Prognosis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Extracellular volume fraction (ECV) on magnetic resonance imaging can predict prognosis after aortic valve replacement in patients with aortic stenosis (AS). However, the usefulness of ECV on computed tomography (CT) for patients who have undergone transcatheter aortic valve replacement (TAVR) is unclear, so we investigated whether ECV analysis on CT is associated with clinical outcomes in TAVR candidates.Methods and Results: We analyzed 127 patients with severe AS who underwent preoperative CT for TAVR. We evaluated the utility of ECV analysis on single-energy CT for predicting patient prognosis after TAVR. The primary outcome was a composite of all-cause death and hospitalization due to heart failure (HF) after TAVR. 15 patients (12%) had composite outcomes: 4 deaths and 11 hospitalizations due to HF. In multivariate survival analysis using the Cox proportional hazard model, atrial fibrillation (AF) (hazard ratio (HR), 7.86; 95% confidence interval (CI), 2.57-24.03; P<0.001), history of congestive HF (HR, 4.91; 95% CI, 1.49-16.2; P=0.009) and ECV ≥32.6% on CT (HR, 6.96; 95% CI, 1.92-25.12; P=0.003) were independent predictors of composite outcomes. On Kaplan-Meier analysis, the higher ECV group (≥32.6%) had a significantly greater number of composite outcomes than the lower ECV group (P<0.001). CONCLUSIONS: ECV on CT is an independent predictor of prognosis after TAVR.

Quantitating myocardial fibrosis using extracellular extravascular volume determined from computed tomography myocardial perfusion imaging.

PURPOSE: Both of extracellular extravascular volume (EEV) and extracellular volume fraction (ECV) were proposed to quantify enlargement of myocardial interstitial space due to myocardium loss or fibrosis. The study aimed to investigate the feasibility of using EEV derived from myocardial computed tomography (CT) perfusion imaging (VPCT) and extracellular volume quantification with single-energy subtraction CT (ECV- SECT) for quantifying myocardial fibrosis. METHODS: In this study, 17 patients with suspected and known coronary artery disease underwent examination using a dual-source CT scanner. The EEV- VPCT was derived from dynamic whole-heart myocardial perfusion imaging, and the ECV_SECT was calculated from late-enhanced images 5 min after bolus contrast injection by subtracting the noncontrast baseline. The late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging was used as a reference. RESULTS: In total, 11 patients and 73 segments exhibited positivity for LGE on CMR imaging. These were classified into three groups according to the segments: fibrotic segments (group I, n = 73), nonfibrotic segments in LGE-positive patients (group II, n = 103), and segments in LGE-negative patients (group III, n = 80). ECV- SECT, EEV- VPCT, myocardial blood flow (MBF), and myocardial blood volume (MBV) significantly differed among these groups (all P < 0.05). ECV- SECT was significantly higher and EEV- VPCT, MBF, and MBV were significantly lower in fibrotic myocardial segments than in nonfibrotic ones (all P < 0.01). ECV- SECT and EEV- VPCT independently affected myocardial fibrosis. There was no significant correlation between ECV- SECT and EEV- VPCT. The capability of EEV- VPCT to diagnose myocardial fibrosis was equivalent to that of ECV- SECT (area under the curve: 0.798 vs. 0.806, P = 0.844). ECV- SECT of > 41.2% and EEV- VPCT of < 10.3% indicated myocardial fibrosis. CONCLUSIONS: EEV- VPCT is actually first-pass distribution volume that can feasibly be used to quantify myocardial fibrosis. Furthermore, the diagnostic efficacy of EEV- VPCT is comparable to that of ECV- SECT.

Extracellular volume fraction of liver and pancreas using spectral CT in hypertensive patients: A comparative study.

BACKGROUND: Besides the direct impact on the cardiovascular system, hypertension is closely associated with organ damage in the kidneys, liver, and pancreas. Chronic liver and pancreatic damage in hypertensive patients may be detectable via imaging. OBJECTIVE: To explore the correlation between hypertension-related indicators and extracellular volume fraction (ECV) of liver and pancreas measured by iodine maps, and to evaluate corresponding clinical value in chronic damage of liver and pancreas in hypertensive patients. METHODS: A prospective study from June to September 2023 included abdominal patients who underwent contrast-enhanced spectral CT. Normal and various grades of hypertensive blood pressure groups were compared. Upper abdominal iodine maps were constructed, and liver and pancreatic ECVs calculated. Kruskal-Wallis and Spearman analyses evaluated ECV differences and correlations with hypertension indicators. RESULTS: In 300 patients, hypertensive groups showed significantly higher liver and pancreatic ECV than the normotensive group, with ECV rising alongside hypertension severity. ECVliver displayed a stronger correlation with hypertension stages compared to ECVpancreas. Regression analysis identified hypertension severity as an independent predictor for increased ECV. CONCLUSIONS: ECVliver and ECVpancreas positively correlates with hypertension indicators and serves as a potential clinical marker for chronic organ damage due to hypertension, with ECVliver being more strongly associated than ECVpancreas.

T1 mapping and extracellular volume fraction measurement to evaluate the poor-prognosis factors in patients with cervical squamous cell carcinoma.

PURPOSE: To evaluate the clinical feasibility of T1 mapping and extracellular volume fraction (ECV) measurement in assessing prognostic factors in patients with cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: A total of 117 CSCC patients and 59 healthy volunteers underwent T1 mapping and diffusion-weighted imaging (DWI) on a 3 T system. Native T1 , contrast-enhanced T1 , ECV, and apparent diffusion coefficient (ADC) were calculated and compared based on surgico-pathologically verified deep stromal infiltration, parametrial invasion (PMI), lymphovascular space invasion (LVSI), lymph node metastasis, stage, histologic grade, and the Ki-67 labeling index (LI). RESULTS: Native T1 , contrast-enhanced T1 , ECV, and ADC values were significantly different between CSCC and the normal cervix (all p < 0.05). No significant differences were observed in any parameters of CSCC when the tumors were grouped by stromal infiltration or lymph node status, respectively (all p > 0.05). In subgroups of the tumor stage and PMI, native T1 was significantly higher for advanced-stage (p = 0.032) and PMI-positive CSCC (p = 0.001). In subgroups of the grade and Ki-67 LI, contrast-enhanced T1 was significantly higher for high-grade (p = 0.012) and Ki-67 LI ≥ 50% tumors (p = 0.027). ECV was significantly higher in LVSI-positive CSCC than in LVSI-negative CSCC (p < 0.001). ADC values showed a significant difference for the grade (p < 0.001) but none for the other subgroups. CONCLUSION: Both T1 mapping and DWI could stratify the CSCC histologic grade. In addition, T1 mapping and ECV measurement might provide more quantitative metrics for noninvasively predicting poor prognostic factors and aiding in preoperative risk assessment in CSCC patients.

Preliminary MRI Study of Extracellular Volume Fraction for Identification of Lymphovascular Space Invasion of Cervical Cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) is a risk factor for poor prognosis of cervical cancer. Preoperative identification of LVSI is very difficult. PURPOSE: To evaluate the potential of extracellular volume (ECV) fraction based on T1 mapping in preoperative identification of LVSI in cervical cancer compared with dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Retrospective. SUBJECTS: A total of 79 patients (median age 54 years) with cervical cancer were classified into LVSI group (n = 29) and without LVSI group (n = 50) according to postoperative pathology. FIELD STRENGTH/SEQUENCE: A 3-T, noncontrast and contrast-enhanced T1 mapping performed with volume interpolated breath hold examination (VIBE) sequence, DCE-MRI applied with 3D T1-weighted VIBE sequence. ASSESSMENT: Regions of interest along the medial edge of the lesion were drawn on slices depicting the maximum cross-section of the tumor. The noncontrast and contrast-enhanced T1 value of the tumor and arteries in the same slice were measured, and ECV was calculated from T1 values. The parametric maps (Ktrans , kep , and ve ) derived from DCE-MRI standard Toft's model were evaluated. STATISTICAL TESTS: ECV, Ktrans , kep , and ve between groups with and without LVSI were compared using Student's t-test. The receiver operating characteristic (ROC) curve and DeLong test were used to evaluate and compare the diagnostic performance of ECV, Ktrans , kep , and ve for differentiating LVSI. P < 0.05 was considered statistically significant. RESULTS: The ECV and Ktrans of the LVSI group were significantly higher than that of non-LVSI group (52.86% vs. 36.77%, 0.239 vs. 0.176, respectively), and no significant differences in Kep or ve values were observed (P = 0.071 and P = 0.168, respectively). The ECV fraction showed significantly higher area under ROC curve than Ktrans for differentiating LVSI (0.874 vs. 0.655, respectively). DATA CONCLUSION: ECV measurements based on T1 mapping might improve the discrimination between patients with and without LVSI in cervical cancer, showing better performance for this purpose than DCE-MRI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Early detection of myocardial fibrosis in cardiomyopathy in the absence of late enhancement: role of T1 mapping and extracellular volume analysis.

OBJECTIVES: To analyze myocardial fibrosis in dilated cardiomyopathy (DCM) patients with no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) using T1 mapping and extracellular volume (ECV) and investigate the potential correlation with left ventricular (LV) dilation and dysfunction. METHODS: The study included 41 DCM patients without LGE and 79 healthy controls. T1 and ECV were compared between the two groups using multivariable logistic regression analysis. The correlations between histological and functional parameters were evaluated using Pearson's correlation. RESULTS: Mean native myocardial T1 and ECV were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). Multivariable logistic regression revealed that ECV (mean, minimum), LV ejection fraction (LVEF), and LV end-diastolic diameter (LVEDD) were independent discriminators for LGE-negative DCM; the area under the curve (AUC) of LVEF, LVEDD, ECV mean, and ECV minimum were 0.97, 0.96, 0.88, and 0.68, respectively. In the DCM group, LVEDD and LVEF were positively and negatively correlated with ECV, respectively. LVEDV index and LV end-systolic volume (LVESV) index were positively correlated with native-T1 and ECV, and the absolute value of LV global strain had a negative correlation with ECV. CONCLUSIONS: Early myocardial fibrosis in DCM could be detected by prolonged native T1 and elevated ECV despite the absence of LGE on CMR. Moreover, the change of histological characteristics of myocardium in DCM was correlated with LV dilation and dysfunction. KEY POINTS: • At an early stage, patients with DCM may have myocardial fibrosis despite the absence of LGE. • T1 mapping and ECV are efficient methods for early detection of potential myocardial fibrosis. • Increased native T1 and ECV are correlated with left ventricular dilation and dysfunction in LGE-negative DCM patients.

A novel cardiac magnetic resonance-based personalized risk stratification model in dilated cardiomyopathy: a prospective study.

OBJECTIVES: To explore individual weight of cardiac magnetic resonance (CMR) metrics to predict mid-term outcomes in patients with dilated cardiomyopathy (DCM), and develop a risk algorithm for mid-term outcome based on CMR biomarkers. MATERIALS AND METHODS: Patients with DCM who underwent CMR imaging were prospectively enrolled in this study. The primary endpoint was a composite of heart failure (HF) death, sudden cardiac death (SCD), aborted SCD, and heart transplantation. RESULTS: A total of 407 patients (age 48.1 ± 13.8 years, 331 men) were included in the final analysis. During a median follow-up of 21.7 months, 63 patients reached the primary endpoint. NYHA class III/IV (HR = 2.347 [1.073-5.133], p = 0.033), left ventricular ejection fraction (HR = 0.940 [0.909-0.973], p < 0.001), late gadolinium enhancement (LGE) > 0.9% and ≤ 6.6% (HR = 3.559 [1.020-12.412], p = 0.046), LGE > 6.6% (HR = 6.028 [1.814-20.038], p = 0.003), and mean extracellular volume (ECV) fraction ≥ 32.8% (HR = 5.922 [2.566-13.665], p < 0.001) had a significant prognostic association with the primary endpoints (C-statistic: 0.853 [0.810-0.896]). Competing risk regression analyses showed that patients with mean ECV fraction ≥ 32.8%, LGE ≥ 5.9%, global circumferential strain ≥ - 5.6%, or global longitudinal strain ≥ - 7.3% had significantly shorter event-free survival due to HF death and heart transplantation. Patients with mean ECV fraction ≥ 32.8% and LGE ≥ 5.9% had significantly shorter event-free survival due to SCD or aborted SCD. CONCLUSION: ECV fraction may be the best independently risk factor for the mid-term outcomes in patients with DCM, surpassing LVEF and LGE. LGE has a better prognostic value than other CMR metrics for SCD and aborted SCD. The risk stratification model we developed may be a promising non-invasive tool for decision-making and prognosis. CLINICAL RELEVANCE STATEMENT: "One-stop" assessment of cardiac function and myocardial characterization using cardiac magnetic resonance might improve risk stratification of patients with DCM. In this prospective study, we propose a novel risk algorithm in DCM including NYHA functional class, LVEF, LGE, and ECV. KEY POINTS: • The present study explores individual weight of CMR metrics for predicting mid-term outcomes in dilated cardiomyopathy. • We have developed a novel risk algorithm for dilated cardiomyopathy that includes cardiac functional class, ejection fraction, late gadolinium enhancement, and extracellular volume fraction. • Personalized risk model derived by CMR contributes to clinical assessment and individual decision-making.

Clinical manifestations and MRI features of Danon disease: a case series.

BACKGROUND: Danon disease (DD) is an exceptionally uncommon X-linked dominant lysosomal glycogen storage disorder characterized by pronounced ventricular hypertrophy and cardiac insufficiency. The timely identification of cardiac impairment in individuals with DD holds significant clinical importance. CASE PRESENTATION: We present a case of Danon Disease in a three-generation pedigree from Anhui Province, China. Clinical features and laboratory data were collected and analyzed for a 16-year-old male proband (III-1) and two affected female family members (II-2 and II-3). The proband exhibited Wolf-Parkinson-White syndrome, hypertrophic cardiomyopathy, abnormal cognitive function, and muscle weakness. Gene sequencing confirmed a mutation (c.963G > A) in the LAMP-2 gene. CONCLUSION: Patients with DD may present both dilated and hypertrophic cardiomyopathy. Comprehensive myocardial tissue characterization by MRI plays a key role in the diagnosis of the disease.

Machine learning to predict left ventricular reverse remodeling by guideline-directed medical therapy by utilizing texture feature of extracellular volume fraction in patients with non-ischemic dilated cardiomyopathy.

Extracellular volume fraction (ECV) by cardiac magnetic resonance (CMR) allows for the non-invasive quantification of diffuse myocardial fibrosis. Texture analysis and machine learning are now gathering attention in the medical field to exploit the ability of diagnostic imaging for various diseases. This study aimed to investigate the predictive value of texture analysis of ECV and machine learning for predicting response to guideline-directed medical therapy (GDMT) for patients with non-ischemic dilated cardiomyopathy (NIDCM). A total of one-hundred and fourteen NIDCM patients [age: 63 ± 12 years, 91 (81%) males] were retrospectively analyzed. We performed texture analysis of ECV mapping of LV myocardium using dedicated software. We calculated nine histogram-based features (mean, standard deviation, maximum, minimum, etc.) and five gray-level co-occurrence matrices. Five machine learning techniques and the fivefold cross-validation method were used to develop prediction models for LVRR by GDMT based on 14 texture parameters on ECV mapping. We defined the LVRR as follows: LVEF increased ≥ 10% points and decreased LVEDV ≥ 10% on echocardiography after GDMT > 12 months. Fifty (44%) patients were classified as non-responders. The area under the receiver operating characteristics curve for predicting non-responder was 0.82 for eXtreme Gradient Boosting, 0.85 for support vector machine, 0.76 for multi-layer perception, 0.81 for Naïve Bayes, 0.77 for logistic regression, respectively. Mean ECV value was the most critical factor among texture features for differentiating NIDCM patients with LVRR and those without (0.28 ± 0.03 vs. 0.36 ± 0.06, p < 0.001). Machine learning analysis using the support vector machine may be helpful in detecting high-risk NIDCM patients resistant to GDMT. Mean ECV is the most crucial feature among texture features.

Heart failure with mildly reduced ejection fraction: emerging frontiers in clinical characteristics, prognosis, and treatment.

Heart failure (HF) is a complex clinical syndrome resulting from the impairment of ventricular filling or ejection of blood or both, leading to considerable morbidity and mortality. Based on left ventricular ejection fraction (LVEF), the 2016 European Society of Cardiology (ESC) guideline firstly classified patients with LVEF in the range of 40% to 49% into heart failure with mid-range ejection fraction. Since then, more and more clinical studies targeting HF with mid-range ejection fraction emerged, indicating that they may benefit from similar therapies to those with LVEF ≤40%. So the latest ESC guideline of HF changed the term 'heart failure with mid-range ejection fraction' to 'heart failure with mildly reduced ejection fraction' (HFmrEF). Simultaneously, burgeoning evidence indicating the emergence of novel technologies (such as speckle tracking echocardiography, cardiac magnetic resonance quantitative imaging), and new biomarkers were conducive to evaluating HF from different perspectives. In this review, we summarized the research progress of HFmrEF in clinical characteristics, prognosis, and treatment, hoping to help cardiologists better evaluate and treat patients of HFmrEF.

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.

Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.

BACKGROUND: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH). METHODS: Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics. RESULTS: Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise. CONCLUSIONS: Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Native T1 heterogeneity for predicting reverse remodeling in patients with non-ischemic dilated cardiomyopathy.

A recent study has shown that the heterogeneity of native T1 mapping may be a new prognostic factor for patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aimed to investigate the predictive value of native T1 heterogeneity of the left ventricular (LV) myocardium, as assessed by pixel-wise histogram analysis, for predicting left ventricular reverse remodeling (LVRR) by medical therapy in patients with NIDCM. A total of one hundred and thirteen NIDCM patients (mean age: 63 ± 12 years; 91 males and 22 females; mean LV ejection fraction (EF): 37 ± 10%) were retrospectively analyzed. T1 mapping images were acquired using a modified look-locker inversion recovery (MOLLI) sequence. We performed histogram analysis of native T1 mapping of LV myocardium, mean (T1-mean) and standard deviation (T1-STD) of native T1 time from each pixel were calculated. Extracellular volume fraction (ECV) was also evaluated. LVRR was defined as LVEF increased ≥ 10% points and decrease in LV end-diastolic volume ≥ 10% at 12 months from initiation of medical therapy. Cutoff value of T1-mean and T1-STD was set as median value of each parameter. Sixty (53%) NIDCM patients reached LVRR. Area under the receiver-operating characteristics curve for predicting LVRR was 0.763 (95% confidence interval (CI) 0.679-0.847) for %LGE, 0.757 (95% CI 0.663-0.850) for T1-mean, 0.724 (95% CI 0.625-0.823) for T1-STD, 0.800 (95% CI 0.717-0.882) for ECV, respectively. Proportion of LVRR was significantly lower in NIDCM patients with high T1-mean and high T1-STD (12%) compared to NIDCM with high T1-mean and low T1-STD (65%) (p < 0.001). Adding T1-STD to T1-mean improved AUC from 0.757 to 0.806, comparable to AUC of ECV. Combination of T1-mean and T1-STD, a parameter of heterogeneity of native T1 of the LV myocardium, may be a useful for prediction of LVRR by medical therapy without use of gadolinium contrast for patients with NIDCM.

Low-frequency dominant electrical conductivity imaging of in vivo human brain using high-frequency conductivity at Larmor-frequency and spherical mean diffusivity without external injection current.

Diffusion weighted imaging based on random Brownian motion of water molecules within a voxel provides information on the micro-structure of biological tissues through water molecule diffusivity. As the electrical conductivity is primarily determined by the concentration and mobility of ionic charge carriers, the macroscopic electrical conductivity of biological tissues is also related to the diffusion of electrical ions. This paper aims to investigate the low-frequency electrical conductivity by relying on a pre-defined biological model that separates the brain into the intracellular (restricted) and extracellular (hindered) compartments. The proposed method uses B1 mapping technique, which provides a high-frequency conductivity distribution at Larmor frequency, and the spherical mean technique, which directly estimates the microscopic tissue structure based on the water molecule diffusivity and neurite orientation distribution. The total extracellular ion concentration, which is separated from the high-frequency conductivity, is recovered using the estimated diffusivity parameters and volume fraction in each compartment. We propose a method to reconstruct the low-frequency dominant conductivity tensor by taking into consideration the extracted extracellular diffusion tensor map and the reconstructed electrical parameters. To demonstrate the reliability of the proposed method, we conducted two phantom experiments. The first one used a cylindrical acrylic cage filled with an agar in the background region and four anomalies for the effect of ion concentration on the electrical conductivity. The other experiment, in which the effect of ion mobility on the conductivity was verified, used cell-like materials with thin insulating membranes suspended in an electrolyte. Animal and human brain experiments were conducted to visualize the low-frequency dominant conductivity tensor images. The proposed method using a conventional MRI scanner can predict the internal current density map in the brain without directly injected external currents.

Performance of Synthetic Extracellular Volume Fraction in Different Cardiac Phenotypes From a Prospective Cohort of Patients Referred for Cardiac Magnetic Resonance.

BACKGROUND: A synthetic myocardial extracellular volume fraction (sECV) can be obtained without blood hematocrit (Hct) by using the linear relationship between Hct and the longitudinal relaxation time of blood. Concerns have been raised about the widespread clinical application of this approach. PURPOSE: To assess the relationship between measured ECV (m-ECV) and sECV, using both a published model and a locally derived one. STUDY TYPE: Single-center, prospective. FIELD STRENGTH/SEQUENCE: A 1.5 T/modified Look Locker (MOLLI) sequence. SUBJECTS: Fifty-two healthy subjects and 113 patients (76 with and 37 without a hypertrophic cardiac phenotype). ASSESSMENT: Three ECV values were obtained for each patient: 1) measured ECV (m-ECV), using Hct from a venous blood sample; 2) Fent-synthetic ECV (F-sECV), using the equation proposed by Fent et al; and 3) Local-synthetic ECV (L-sECV), using the equation obtained from a local derivation cohort comprising 83 subjects. STATISTICAL TESTS: Shapiro-Wilk test, analysis of variance, Kruskal Wallis test, Pearson correlation, Bland-Altman analysis, univariate and multivariable regression analysis. RESULTS: In the validation cohort (N = 82), Bland-Altmann analysis revealed an excellent agreement between m-ECV and L-sECV with a statistically insignificant bias (-0.1%, limits of agreement: -2.8% and 2.6%; P = 0.528), while in the overall population (N = 165), the mean bias between m-ECV and F-sECV was small but significant (1.2%, limits of agreement: -1.5% and 3.9%, P < 0.05). F-sECV bias was significantly higher for measured Hct (m-Hct) values <0.372 (2.3% vs. 1.0%, P < 0.05). Among the phenotype subgroups, amyloidotic patients showed a higher bias compared to others, both with F-sECV and L-sECV (2.3% vs. 1.1%, P < 0.05 and 1.1% vs. 0.2%, P < 0.05, respectively). DATA CONCLUSION: Although synthetic ECV performs well in an external cohort, the use of a local formula further improves the accuracy of ECV estimate over a broad spectrum of cardiac phenotypes. Local sECV performs better for a wider range of Hct values, compared to the published model. Amyloidosis is the only group associated with a lower accuracy. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms.

BACKGROUND: /Objectives: Identifying reliable pretreatment imaging biomarkers for pancreatic neuroendocrine neoplasm (PanNEN) is a key imperative. Extracellular volume (ECV) fraction quantified with equilibrium contrast-enhanced CT can be easily integrated into routine examinations. This study aimed to determine whether ECV fraction with equilibrium contrast-enhanced computed tomography (CECT) could predict long-term outcomes in patients with PanNEN. METHODS: This study was a retrospective observational study of 80 patients pathologically diagnosed with PanNEN at a single institution. ECV fraction of the primary lesion was calculated using region-of-interest measurement within PanNEN and the aorta on unenhanced and equilibrium CECT. The impact of clinical factors and tumor ECV fraction on progression-free survival (PFS) and overall survival (OS) was assessed with univariate and multivariate analyses using Cox proportional hazards models. The correlation between WHO classification and tumor ECV fraction was evaluated using Kendall rank correlation coefficients. RESULTS: PFS and OS rates were estimated as 93.4% and 94.6%, 78.7% and 86.2%, 78.7% and 77.0%, and 78.7% and 66.6% at 1, 3, 5, and 10 years, respectively. Multivariate analysis revealed that Union for International Cancer Control (UICC) stage (hazard ratio [HR] = 3.95, P = 0.003), WHO classification (HR = 12.27, P = 0.003), and tumor ECV fraction (HR = 11.93, P = 0.039) were independent predictors of PFS. Patient age (HR = 1.11, P < 0.001), UICC stage (HR = 3.14, P = 0.001), and tumor ECV fraction (HR = 5.27, P = 0.024) were independent significant variables for predicting OS. Tumor ECV fraction had a weak inverse relationship with WHO classification (P = 0.045, τ = -0.178). CONCLUSIONS: ECV fraction determined by equilibrium CECT and UICC stage may predict survival in patients with PanNEN.

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

BACKGROUND: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. METHODS: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro-) was performed. RESULTS: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro- patients. CONCLUSIONS: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. TRIAL REGISTRATION: This trial is registered at the local institutional ethics committee (S-188/2018).

Electrocardiogram-less, free-breathing myocardial extracellular volume fraction mapping in small animals at high heart rates using motion-resolved cardiovascular magnetic reesonance multitasking: a feasibility study in a heart failure with preserved ejection fraction rat model.

BACKGROUND: Extracellular volume fraction (ECV) quantification with cardiovascular magnetic resonance (CMR) T1 mapping is a powerful tool for the characterization of focal or diffuse myocardial fibrosis. However, it is technically challenging to acquire high-quality T1 and ECV maps in small animals for preclinical research because of high heart rates and high respiration rates. In this work, we developed an electrocardiogram (ECG)-less, free-breathing ECV mapping method using motion-resolved CMR Multitasking on a 9.4 T small animal CMR system. The feasibility of characterizing diffuse myocardial fibrosis was tested in a rat heart failure model with preserved ejection fraction (HFpEF). METHODS: High-salt fed rats diagnosed with HFpEF (n = 9) and control rats (n = 9) were imaged with the proposed ECV Multitasking technique. A 25-min exam, including two 4-min T1 Multitasking scans before and after gadolinium injection, were performed on each rat. It allows a cardiac temporal resolution of 20 ms for a heart rate of ~ 300 bpm. Myocardial ECV was calculated from the hematocrit (HCT) and fitted T1 values of the myocardium and the blood pool. Masson's trichrome stain was used to measure the extent of fibrosis. Welch's t-test was performed between control and HFpEF groups. RESULTS: ECV was significantly higher in the HFpEF group (22.4% ± 2.5% vs. 18.0% ± 2.1%, P = 0.0010). A moderate correlation between the ECV and the extent of fibrosis was found (R = 0.59, P = 0.0098). CONCLUSIONS: Motion-resolved ECV Multitasking CMR can quantify ECV in the rat myocardium at high heart rates without ECG triggering or respiratory gating. Elevated ECV found in the HFpEF group is consistent with previous human studies and well correlated with histological data. This technique has the potential to be a viable imaging tool for myocardial tissue characterization in small animal models.