Liver Extracellular Volume Research Articles

MRI Extracellular Volume Fraction in Liver Fibrosis-A Comparison of Different Time Points and Blood Pool Measurements.

Extracellular volume (ECV) correlates with the degree of liver fibrosis. To analyze the performance of liver MRI-based ECV evaluations with different blood pool measurements at different time points. Prospective. 73 consecutive patients (n = 31 females, mean age 56 years) with histopathology-proven liver fibrosis. 3T acquisition within 90 days of biopsy, including shortened modified look-locker inversion recovery T1 mapping. Polygonal regions of interest were manually drawn in the liver, aorta, vena cava, and in the main, left and right portal vein on four slices before and after Gd-DOTA administration at 5/10/15 minutes. ECV was calculated 1) on one single slice on portal bifurcation level, and 2) averaged over all four slices. Parameters were compared between patients with fibrosis grades F0-2 and F3-F4 with the Mann-Whitney U and fishers exact test. ROC analysis was used to assess the performance of the parameters to predict F3-4 fibrosis. A P-value <0.05 was considered statistically significant. ECV was significantly higher in F3-4 fibrosis (35.4% [33.1%-37.6%], 36.1% [34.2%-37.5%], and 37.0% [34.8%-39.2%] at 5/10/15 minutes) than in patients with F0-2 fibrosis (33.3% [30.8%-34.8%], 33.7% [31.6%-34.7%] and 34.9% [32.2%-36.0%]; AUC = 0.72-0.75). Blood pool T1 relaxation times in the aorta and vena cava were longer on the upper vs. lower slices at 5 minutes, but not at 10/15 minutes. AUC values were similar when measured on a single slice (AUC = 0.69-0.72) or based on blood pool measurements in the cava or portal vein (AUC = 0.63-0.67 and AUC = 0.65-0.70). Liver ECV is significantly higher in F3-4 fibrosis compared to F0-2 fibrosis with blood pool measurements performed in the aorta, inferior vena cava, and portal vein at 5, 10, and 15 minutes. However, a smaller variability was observed for blood pool measurements between slices at 15 minutes. 1 TECHNICAL EFFICACY: Stage 3.

Liver T1 Mapping Derived From Cardiac Magnetic Resonance Imaging: A Potential Prognostic Marker in Idiopathic Dilated Cardiomyopathy.

Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. Prospective. Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. 1 TECHNICAL EFFICACY: Stage 2.

Tracking multi-organ treatment response in systemic AL amyloidosis with cardiac magnetic resonance derived extracellular volume mapping

Abstract Funding Acknowledgements Type of funding sources: None. Background Systemic light-chain (AL) amyloidosis commonly involves the liver, spleen and heart. Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping has demonstrated accuracy in measuring cardiac, hepatic and splenic amyloid infiltration. Purpose We sought to: (1) assess the association between baseline multi-organ ECVs and prognosis (2) assess the multi-organ response to treatment using ECV mapping, and (3) assess the association between multi-organ treatment response and prognosis. Methods We identified 351 patients with a confirmed diagnosis of systemic AL amyloidosis who underwent baseline serum amyloid P component (SAP) scintigraphy and CMR at diagnosis, of which 171 had follow-up imaging. We also recruited 20 healthy volunteers who underwent CMR with ECV mapping, without corresponding SAP scintigraphy, to allow calculation of the ECV normal ranges. Results At diagnosis, ECV mapping demonstrated that 304(86.7%) had cardiac involvement, 114(32.5%) significant hepatic involvement and 147(41.9%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial: HR=1.05,95CI%[1.03–1.07],P&amp;lt;0.001; liver: HR=1.03,95%CI[1.01–1.05],P&amp;lt;0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R=0.751,P&amp;lt;0.001; R=0.765,P&amp;lt;0.001, respectively). Serial multi-organ ECV measurements accurately tracked treatment response as validated against serial SAP scintigraphy (the current reference standard). Multi-organ ECV regression was observed as early as 6-months in patients with a good haematological response (liver=15%, spleen=15%, heart=5%). The remaining patients with a good haematological response had stable liver and spleen ECVs, but 20% had cardiac progression. By 12-months more patients with a good haematological response demonstrated cardiac regression (liver=30%, spleen=36%, heart=32%), and this trend was maintained at 24-months. Multi-variable analysis adjusting for haematological response, change in myocardial, liver and spleen ECV demonstrated that haematological response, change in myocardial ECV (HR=1.11, 95%CI[1.02–1.19], P=0.011) and liver ECV (HR=1.06, 95%CI[1.01–1.11], P=0.015) remained independent predictors of prognosis at 6-months. Conclusions Multi-organ ECV quantification accurately tracks treatment response, and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. A good haematological response alone is likely to induce visceral organ stabilisation/regression, but may not be sufficient to induce myocardial stabilisation/regression. Liver and myocardial ECV at diagnosis and changes in ECV at 6-months independently predict mortality. ECV mapping offers a comprehensive multi-organ assessment of treatment response and accurate prognostication.

Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping

BackgroundSystemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden. ObjectivesThe purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis. MethodsThe authors identified 351 patients who underwent baseline serum amyloid-P-component (SAP) scintigraphy and cardiac magnetic resonance at diagnosis, of which 171 had follow-up imaging. ResultsAt diagnosis, ECV mapping demonstrated that 304 (87%) had cardiac involvement, 114 (33%) significant hepatic involvement, and 147 (42%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial HR: 1.03 [95% CI: 1.01-1.06]; P = 0.009; liver HR: 1.03; [95% CI: 1.01-1.05]; P = 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R = 0.751; P < 0.001; R = 0.765; P < 0.001, respectively). Serial measurements demonstrated ECV correctly identified changes in liver and spleen amyloid load derived from SAP scintigraphy in 85% and 82% of cases, respectively. At 6 months, more patients with a good hematologic response had liver (30%) and spleen (36%) ECV regression than myocardial regression (5%). By 12 months, more patients with a good response demonstrated myocardial regression (heart 32%, liver 30%, spleen 36%). Myocardial regression was associated with reduced median N-terminal pro-brain natriuretic peptide (P < 0.001), and liver regression with reduced median alkaline phosphatase (P = 0.001). Changes in myocardial and liver ECV, 6 months after initiating chemotherapy, independently predict mortality (myocardial HR: 1.11 [95% CI: 1.02-1.20]; P = 0.011; liver HR: 1.07 [95% CI: 1.01-1.13]; P = 0.014). ConclusionsMultiorgan ECV quantification accurately tracks treatment response and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Baseline myocardial and liver ECV and changes at 6 months independently predict mortality, even after adjusting for traditional predictors of prognosis.

Abstract 12257: Prognostic Value of Liver T1 Mapping and Extracellular Volume in Dilated Cardiomyopathy

Introduction: Cardiac dysfunction closely correlates with liver congestion and effect on liver relaxation time. Liver relaxometry could provide potential prognostic improvement for dilated cardiomyopathy (DCM) patients. Hypothesis: Liver relaxometry might have prognostic significance for DCM patients. Methods: We prospectively enrolled 433 patients diagnosed with DCM. Cardiac and hepatic T1, T2, and extracellular volume (ECV) were measured on the mid-ventricular mappings. The primary endpoint was defined as heart failure death, sudden cardiac death, and heart transplantation. Results: DCM patients who reached primary endpoint showed significantly increased liver native T1 (770.5±103.2ms versus 813.8±137.0ms, p=0.014) and ECV values (30.9±6.8% versus 34.3±10.7%, p=0.009) and decreased liver T2 value (35.8±5.5 versus 34.1±6.2ms, p=0.038). Right ventricular ejection fraction correlated moderately but significantly with liver native T1 (r =-0.293) and ECV (r=-0.245) (both p&lt;0.001). During the follow-up period (median duration 3.9 years) 97 patients reached the primary endpoint. In the Kaplan-Meier survival analysis, DCM patients with elevated liver native T1 or ECV had higher risk of reaching the primary endpoint (cutoff value: 854.9ms, p=0.001 and cutoff value: 34.5%, p&lt;0.001, respectively). Cox analysis indicated that liver ECV was an independent prognostic factor (hazard ratio:1.042, p&lt;0.001) and showed incremental prognostic value to age, sex, NYHA class III-IV, and LVEF. Conclusions: Liver native T1 and ECV correlates with cardiac magnetic resonance parameters. Furthermore, Liver ECV provides incremental prognostic value in DCM patients.

Comparison of Liver Fibrosis and Function Indices with Extracellular Volume Using Dual-energy CT: A Retrospective Study.

Dual-Energy Computed Tomography (DECT) enables the direct measurement of iodine accumulation in the extracellular space. To compare measures of liver fibrosis and function with Extracellular Volume (ECV) from iodine/water images using DECT. Data was obtained from 119 consecutive patients who underwent abdominal DECT. A region of interest was set in the right lobe of the liver, pancreas, spleen, and aorta on iodine density images. ECV was calculated using the following formula: ECV = (1 - hematocrit) × [iodine concentration in the liver (or pancreas, spleen) / iodine concentration in the aorta]. The severity of liver fibrosis was estimated using the aminotransferase/platelet ratio index (APRI) and the Fibrosis-4 (FIB-4) index. Liver function was assessed by the Child-Pugh classification and albumin-bilirubin (ALBI) grade. Data were analyzed by the Spearman rank correlation coefficient, one-way analysis of variance, and post hoc analysis. The correlation between ECV and fibrosis indices (APRI and FIB-4) was only significant, with a weak magnitude for liver ECV quantification at the equilibrium phase (r=0.25 and r=0.20, respectively). The correlations between liver function index and ECV quantification were more robust than with fibrosis index. The highest correlations (r=0.50) were found between ALBI grade and liver ECV at the equilibrium phase. Liver ECV values at the equilibrium phase had a significant difference between ALBI grade 1 vs. 2 and grade 1 vs. 3. Liver ECV quantification by DECT is more suitable for evaluating liver function than liver fibrosis severity.

Quantification of liver extracellular volume using dual-energy CT for ruling out high-risk varices in cirrhosis

PurposeTo determine the performance of quantification of liver extracellular volume fraction (fECV) using dual-energy CT (DECT) compared with CT imaging for ruling out high-riskesophageal varices(HRV) in cirrhotic patients. MethodsWe retrospectively analyzed 229 cirrhotic patients (training [n = 159] and internal validation cohorts [n = 70]) who underwent dual-source DECT, serum marker assessment, and esophagogastroduodenoscopy (EGD) from 2017 to 2020. The fECV score was measured using iodine maps from 3-minute delayed, equilibrium-phase images at 100/140 Sn kVp. The association of CT parameters and serum markers with HRV was investigated. Criteria combining the fECV score (≤ 25.1%) or CT imaging with platelet count (> 150,000/mm3) were created and compared to rule out HRV. ResultsIn the training cohort, the fECV score (odds ratio (OR), 1.20; 95% confidence interval (CI), 1.09, 1.32) and CT imaging (OR, 28.21; 95% CI, 9.31, 85.93) were independent predictors of HRV, along with platelet count (OR, 0.85 and 0.78). Criteria combining the fECV score with platelet count showed significantly better performance than those combining CT imaging with platelet count in ruling out HRV (p < 0.001). Applying the criteria could have safely avoided an additional 10.7% and 8.6% of EGDs in the training and validation cohorts, respectively, achieving a final value of 36.5% and 35.7% spared EGDs (0 HRV missed) compared to CT imaging with platelet count. ConclusionsThe combined DECT-based fECV score with platelet count is useful for ruling out HRV and can safely avoid more EGDs than CT imaging with platelet count.

Liver magnetic resonance relaxometry can provide useful markers for the assessment of right heart failure in dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In dilated cardiomyopathy (DCM) patients at risk of developing right heart failure (RHF), early depiction of congestive heart failure (CHF) is pivotal to inform about the hemodynamic status and tailor medical therapy. Purpose We hypothesized that increased liver relaxation times measured at routine cardiovascular magnetic resonance (CMR), reflecting passive hepatic congestion, may be a valuable imaging biomarker to depict CHF. Methods The study cohort included DCM patients with (n = 48) and without (n = 46) right ventricular dysfunction (RVD), defined as a right ventricular ejection fraction &amp;lt;35%, and &amp;gt;45%, respectively, and a control group (n = 40). Native T1, T2, and extracellular volume (ECV) liver values were measured on routinely acquired cardiac maps. Results DCM with RVD patients had higher C-reactive protein, troponin I and NT-pro BNP values, and worse LV functional parameters than DCM without RVD patients (all p &amp;lt; 0.001). T1, T2 and ECV liver values were significantly higher in DCM with, compared to DCM without, RVD patients and also compared to controls [T1: 675 ± 88ms vs. 538 ± 39ms and 540 ± 34ms; T2: 54 ± 8ms vs. 45 ± 5ms and 46 ± 4ms; ECV: 36 ± 7% vs. 29 ± 4% and 30 ± 3%, respectively (all p &amp;lt; 0.001)]. Gamma glutamyltranspeptidase (γGT) correlated moderately but significantly with liver native T1 (r2 =0.34), T2 (r2 =0.27), and ECV (r2 =0.23) (all p &amp;lt; 0.001). Using right atrial pressure (RAP &amp;gt; 5 mmHg), as a surrogate measure of RHF, liver native T1 yielded at ROC analysis the highest AUC (0.906), significantly higher than liver ECV (0.813), γGT (0.806), liver T2 (0.797), total bilirubin (0.737) and alkaline phosphatase (0.561) [Figure 1]. A liver native T1 value of 617 ms showed a sensitivity of 79.5% and a specificity of 91.0% in identifying RHF. Density plots to discriminate between presence and absence of RHF are demonstrated at Figure 2. Excellent intra-/inter-observer agreement was found for assessment of native T1/T2/ECV liver values. Conclusion In DCM patients, assessment of liver relaxation times acquired on a CMR exam, may provide valuable information with regard to the presence of RHF.

Cardiac Magnetic Resonance-Derived Extracellular Volume Mapping for the Quantification of Hepatic and Splenic Amyloid.

Systemic amyloidosis is characterized by amyloid deposition that can involve virtually any organ. Splenic and hepatic amyloidosis occurs in certain types, in some patients but not others, and may influence prognosis and treatment. SAP (serum amyloid P component) scintigraphy is uniquely able to identify and quantify amyloid in the liver and spleen, thus informing clinical management, but it is only available in 2 centers globally. The aims of this study were to examine the potential for extracellular volume (ECV) mapping performed during routine cardiac magnetic resonance to: (1) detect amyloid in the liver and spleen and (2) estimate amyloid load in these sites using SAP scintigraphy as the reference standard. Five hundred thirty-three patients referred to the National Amyloidosis Centre, London, between 2015 and 2017 with suspected systemic amyloidosis who underwent SAP scintigraphy and cardiac magnetic resonance with T1 mapping were studied. The diagnostic performance of ECV to detect splenic and hepatic amyloidosis was high for both organs (liver: area under the curve, -0.917 [95% CI, 0.880-0.954]; liver ECV cutoff, 0.395; sensitivity, 90.7%; specificity, 77.7%; P<0.001; spleen: area under the curve, -0.944 [95% CI, 0.925-0.964]; spleen ECV cutoff, 0.385; sensitivity, 93.6%; specificity, 87.5%; P<0.001). There was good correlation between liver and spleen ECV and amyloid load assessed by SAP scintigraphy (r=0.504, P<0.001; r=0.693, P<0.001, respectively). There was high interobserver agreement for both the liver and spleen (ECV liver intraclass correlation coefficient, 0.991 [95% CI, 0.984-0.995]; P<0.001; ECV spleen intraclass correlation coefficient, 0.995 [95% CI, 0.991-0.997]; P<0.001) with little bias across a wide range of ECV values. Our study demonstrates that ECV measurements obtained during routine cardiac magnetic resonance scans in patients with suspected amyloidosis can identify and measure the magnitude of amyloid infiltration in the liver and spleen, providing important clues to amyloid type and offering a noninvasive measure of visceral amyloid burden that can help guide and track treatment.

Quantitative assessment of disease severity of primary sclerosing cholangitis with T1 mapping and extracellular volume imaging.

Assess the relationship between liver T1 relaxation time and extracellular volume (ECV) fraction and the disease severity of primary sclerosing cholangitis (PSC). This retrospective study included 93 patients with PSC and 66 healthy patients in the control group. T1 relaxation times were measured in the right and left lobe, as well as in the area of stricture. T1PSC and ECVPSC were calculated by averaging T1 and ECV of both lobes and stricture site. T1 and ECV were compared between the two groups and according to PSC phenotypes and severity based on Mayo Risk Score (MRS). We also examined the relationship between T1 and ECV with non-invasive measures of fibrosis such as Fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM) by transient elastography. Mean liver T1 (774 ± 111ms, p < 0.001) and liver ECV (0.40 ± 0.14, p < 0.05) were significantly higher with both large-duct and small-duct-type PSC which may lack classic imaging findings on MRCP compared to the control group (p < 0.001). T1PSC and ECVPSC showed weak-moderate correlation with LSM, FIB-4, and MRS (p < 0.05). Cut-off values of liver T1 to detect patients in low-risk and high-risk MRS groups were 677ms (AUC: 0.68, sensitivity: 76%, specificity: 53%, p = 0.03) and 743ms (AUC: 0.83, sensitivity: 79%, specificity: 76%, p < 0.001), respectively. T1 relaxation time and ECV fraction can be used for quantitative assessment of disease severity in patients with PSC.

Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy.

Fibrogenesis and inflammation contribute to the progression of cirrhosis. However, it is unknown if these processes also contribute to the development of cirrhotic cardiomyopathy (CCM). Novel magnetic resonance imaging with quantification of the extracellular volume (ECV) provides an estimate of the fibrotic remodelling in the liver and heart. To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation. A prospective study of 52 patients with cirrhosis and 14 healthy controls. All patients underwent contrast-enhanced MRI with T1-mapping and quantification of myocardial and liver ECV, biochemical assessments of collagen turnover (PRO-C3, PRO-C5, PRO-C6, collagen type IV degradation fragment, collagen type V degradation fragment, LG1M) and inflammation (TNFα, IL-1β, IL-6, IL-8, IL-18, SDF1α, sCD163, sMR, soluble macrophage mannose receptor). Myocardial and liver ECV were increased in patients compared with healthy controls (myocardial ECV 31.2±5.5% vs 27.4±2.9%, P=0.037; liver ECV 44.1±9.6% vs 33.7±6.7%, P<0.001). Myocardial ECV correlated strongly with liver ECV (r=0.48, P=0.001) and biomarkers of collagen formation and inflammation (P<0.005). Similarly, liver ECV correlated with biomarkers of collagen formation and inflammation (P<0.003). In a multivariate analysis, liver ECV was predicted by biomarkers of collagen formation (PRO-C3 and PRO-C6), whereas myocardial ECV was predicted by biomarkers of collagen formation (PRO-C6) and inflammation (IL-6 and sMR). Structural myocardial changes seem closely related to liver fibrosis in patients with cirrhosis. The strong associations with biomarkers of collagen formation and inflammation provide new insight into the role of inflammation and fibrogenesis in the development of structural cardiac abnormalities, potentially leading to CCM.

Liver extracellular volume fraction values obtained with magnetic resonance imaging can quantitatively stage liver fibrosis: a validation study in monkeys with nonalcoholic steatohepatitis.

This study was to evaluate the diagnostic value of liver extracellular volume (LECV) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (NASH). Forty-eight cynomolgus monkeys were enrolled in this prospective study. There are 17 healthy monkeys and 31 monkeys with NASH. Ten of these monkeys were used for repeatability assessment. The remaining 38 monkeys were used to compare LECV with other indicators including pathology fibrosis score, native T1, and serum chemical indexes by Spearman, Pearson correlation test, and ROC curves. The inter-reader variability was assessed by interclass correlation. The repeatability measurement of LECV was analyzed using Bland-Altman plots and the coefficient of variation. Partial correlation analysis was performed to assess the effects of fat content and inflammation scores on the correlation between LECV/T1 and liver fibrosis score. This study demonstrated a good intra-reader agreement (intraclass correlation = 0.79) of LECV in all monkeys and an excellent repeatability in 10 monkeys (coefficient of variation = 2.01%). The LECV has a strong correlation with the fibrosis score (r = 0.949; p < 0.0001), low-density lipoprotein (r = 0.72; p < 0.0001), and cholesterol (r = 0.70; p < 0.0001). LECV showed high diagnostic efficacy in the diagnosis of liver fibrosis (area under the curve of ROC, 0.945~1; p < 0.001). LECV may serve as a noninvasive valuable biomarker for the quantification and differentiating of the non-severe liver fibrosis (stage ≤ F3). However, circulating serum markers low-density lipoprotein and cholesterol (CHO) may not serve for this purpose. • This paper demonstrated the excellent repeatability (intraclass correlation coefficient = 0.79) of LECV in monkey animal model. • LECV-MRI has a strong correlation with histopathological fibrosis score stage (r = 0.949; p < 0.0001) and shows high diagnostic efficacy in the staging of non-severe liver fibrosis (the area under ROC curve ≥ 0.945). • The new fibrosis score maps appeared to provide a better imaging tool for the spatial assessment of liver fibrosis. It may eventually facilitate the diagnosis of liver fibrosis distribution.

Quantification of liver extracellular volume using dual-energy CT: utility for prediction of liver-related events in cirrhosis.

To determine whether quantification of liver extracellular volume fraction (fECV) using dual-energy CT (DECT) allows prediction of liver-related events (LREs) in cirrhotic patients. This retrospective study included 305 cirrhotic patients who underwent dual-source DECT imaging and had serum markers analyzed within 2weeks of initial CT imaging. The fECV score was measured using an iodine map of equilibrium-phase images obtained 3min after contrast injection at 100/140 Sn kVp. The association of the fECV score and serum markers with LREs was investigated. A risk model combining the fECV score (< 27 versus ≥ 27%) and serum albumin level (< 4 versus ≥ 4g/dL) was constructed for LRE prediction. An increased fECV score (odds ratio, 1.27; 95% confidence interval (CI), 1.15, 1.40) was independently associated with decompensated cirrhosis at baseline (n = 85) along with the Model for End-Stage Liver Disease score (odds ratio, 1.32; 95% CI, 1.07, 1.63). Among patients with compensated cirrhosis, 10.5% (23 of 220) experienced LREs during the median follow-up period of 2.0years (decompensation, n = 14; hepatocellular carcinoma, n = 9). The fECV score (hazard ratio, 1.40; 95% CI, 1.22, 1.62) and serum albumin level (hazard ratio, 0.26; 95% CI, 0.09, 0.73) were independent predictors of LRE. The mean times to LRE among the high (16.5months, n = 18)-, intermediate (25.6months, n = 44)-, and low (30.5months, n = 158)-risk groups were significantly different (p < 0.001). The fECV score derived from DECT allows prediction of LREs in cirrhotic patients. • The extracellular volume fraction (fECV) score derived from the iodine map of dual-energy CT (DECT) was independently associated with the presence of hepatic decompensation. • The fECV score derived from the iodine map of DECT can predict liver-related events (LREs) in patients with cirrhosis. • Equilibrium-phase scanning in dual-energy mode is recommended as part of liver CT in cirrhotic patients because it can provide a prognostic indicator for LRE development.

Quantitative Assessment of Extracellular Volume in Doxorubicin-Induced Liver Injury in Beagle Models by Equilibrium Computed Tomography.

The purpose of this study was to determine whether liver extracellular volume (ECV) measured using equilibrium computed tomography (EQ-CT) can be used to quantitatively assess doxorubicin-induced liver injury (DILI). The ethical approval was obtained from the Institutional Animal Care and Use Committee regulations. Thirteen dogs administered with doxorubicin for 0 to 24 weeks were imaged by contrast-enhanced EQ-CT. The dogs were divided into 3 groups: the baseline (13 dogs), 16-week (10 dogs), and 24-week (7 dogs) groups. Pathological analysis of the liver was performed using hematoxylin-eosin and Masson staining. Liver ECV uptake was calculated for each group and correlated with the histopathological and serological findings of hepatic fibrosis (hyaluronic acid and procollagen type III). In the baseline group, the median ECVs of the right and left liver lobes were 21.78% (interquartile range [IQR], 16.78%-26.68%) and 20.91% (IQR, 16.39%-24.07%), respectively. In the 16- and 24-week groups, the median ECVs of these 2 liver lobes were 28.18% (IQR, 20.56%-34.61%) and 25.96% (IQR, 14.07%-41.38%) and 29.71% (IQR, 27.19%-35.25%) and 29.22% (IQR, 22.62%-38.67%), respectively. There were no significant differences in ECV between the left and right lobes in the 3 groups (P < 0.05). Both the 16- and 24-week groups showed significantly higher ECV than did the primary group (P = 0.001-0.0006). However, there were no significant differences in ECV between the 16-week group and 24-week group (P = 0.412). There was a positive correlation between the serum index and edema due to the inflammation and necrosis associated with DILI (R = 0.6534, R = 0.7129). Extracellular volume measured by EQ-CT imaging can accurately predict the potential DILI through the quantification of ECV changes.

Quantification of liver fibrosis: extracellular volume fraction using an MRI bolus-only technique in a rat animal model

BackgroundTo determine the utility of single-contrast-bolus hepatic extracellular volume (ECV) fraction measurement at different time points to detect and quantify hepatic fibrosis.MethodsDifferent grades of liver fibrosis were induced in 23 male Sprague-Dawley rats by carbon-tetrachloride (CCl4) intoxication. In ten control rats, no fibrosis was induced. Native T1 values and ECV fraction were assessed by using quantitative magnetic resonance imaging (MRI) mapping; only one contrast bolus was applied (gadobutrol 0.1 mmol/kg). ECV values were determined 5, 15, and 25 min after injection. Hepatic fibrosis was quantified histologically by Sirius red staining.ResultsFor the 8-week-CCl4 group, the ECV fraction values obtained 5 (23.5 ± 4.8%, mean ± standard deviation), 15 (23.6 ± 4.8%), and 25 min (23.7 ± 4.7%) after injection were constant over time (p = 0.998); constant data 5–25 min after injection were also observed for the 16-week-CCl4 group and controls. Liver ECV after 15 min significantly increased with the severity of fibrosis: 18.0 ± 3.0% (controls) versus 23.6 ± 4.8% (8-week-CCl4) versus 30.5 ± 3.3% (16-week-CCl4) (p < 0.001). ECV values after 5, 15, and 25 min significantly correlated with Sirius red staining (p < 0.001 for all parameters).ConclusionsHepatic ECV obtained using a single-contrast-bolus technique can be measured 5, 15, and 25 min after injection, obtaining constant values over time, each of them being suitable to detect diffuse hepatic fibrosis. In clinical practice, post-contrast T1 relaxation times for liver ECV fraction determination might be obtained at only one time point.

Assessing liver fibrosis in chronic hepatitis B using MR extracellular volume measurements: Comparison with serum fibrosis indices

ObjectivesTo evaluate the diagnostic value of liver extracellular volume (ECVliver) measurement by equilibrium MR in staging liver fibrosis in chronic hepatitis B (CHB) patients, and to compare its performance with serum fibrosis indices. Materials and methods91 CHB patients were included and underwent gadopentetate dimeglumine-enhanced MRI with T1 mapping sequence before and 15-min after contrast. ECVliver, aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated and compared between fibrosis subgroups, and the correlations between the three indices and fibrosis stage or inflammatory activity were measured by Spearman correlation analysis and stepwise multiple regression analysis. Diagnostic performance in evaluating liver fibrosis stage was assessed and compared using receiver operating characteristic analysis. ResultsInterobserver agreement showed an excellent interclass correlation coefficient of 0.895 for ECVliver. ECVliver, APRI and FIB-4 were different between fibrosis stages as a whole (F/H = 18.44–24.36, P ≤ 0.001). ECVliver had the strongest correlation with fibrosis stage (r = 0.727, P < 0.001), while APRI and FIB-4 had weak correlations (r = 0.466 and 0.440, P < 0.001). Multivariate analysis showed that only ECVliver was independently correlated with fibrosis stage (P < 0.001). The fibrosis stage was the only independent factor correlated with ECVliver comparing to inflammatory activity (P < 0.001). AUCs of ECVliver were larger than both APRI and FIB-4 in fibrosis staging, with significant differences in the diagnosis of advanced fibrosis (≥F3) and cirrhosis (F4) (P = 0.0024 to 0.0049). ConclusionMR ECVliver provides a promising noninvasive tool in staging liver fibrosis for CHB patients, superior to the fibrosis indices of APRI and FIB-4.

Study on diagnostic value of extracellular volume imaging by magnetic resonance imaging for liver fibrosis of hepatitis B

Objective: To investigate the diagnostic value of extracellular volume (ECV) imaging by magnetic resonance imaging for liver fibrosis of hepatitis B. Methods: A retrospective analysis was recruited in patients with chronic hepatitis B, who underwent liver surgery from April to October 2017 for pathological evaluation of liver tissues, and all patients underwent Gd-EOB-DTPA-enhanced T1 mapping to calculate the liver ECV score. The correlation between ECV and staging of hepatic fibrosis and inflammatory activity were compared to clarify the diagnostic value of staging of fibrosis. Results: 66 patients were enrolled in this study. Concerning the staging of liver fibrosis, there were 13, 4, 13, 10, and 26 cases with F0, F1, F2, F3 and F4 stages, respectively. ECV values had high interobserver consistency (correlation coefficient 0.860). The ECV difference between different stages of liver fibrosis was statistically significant (F = 15.02, P < 0.001). There was a significant positive correlation between ECV and fibrosis stage (r = 0.622, P < 0.001), and weak correlation with inflammatory activity (r = 0.332, P = 0.007). Fibrosis staging was an independent factor influencing ECV (P < 0.001). The area under the receiver operator characteristic curve for the diagnosis of liver fibrosis staging F≥1, F≥3 and F4 were 0.760, 0.846 and 0.873, respectively. The diagnostic sensitivity and specificity were 64.15%, 92.31%, 77.78%, 80.00% and 88.46, 72.50%, respectively. Conclusion: MRI-ECV imaging has great value for staging hepatic fibrosis of hepatitis B, and it can provide an effective method for diagnosis, staging, and evaluating the curative effect of fibrosis.

Using T1 mapping in cardiovascular magnetic resonance to assess congestive hepatopathy.

The goal of this study was to assess the ability of quantitative T1 cardiovascular magnetic resonance (CMR) imaging to calculate liver extracellular volume (ECV) in patients with varying degrees of congestive hepatopathy (CH). T1 measurements and ECV calculations were performed retrospectively in three cohorts of patients: normal cardiac function, tetralogy of fallot (TOF) repair and Fontan palliation. All CMR studies included modified look-locker inversion recovery (MOLLI) T1 mapping scans performed pre- and post-injection of a gadolinium-based contrast agent (GBCA). Pixel intensity data were manually collected from images of the liver and cardiac blood pool to determine contrast-induced changes in T1 for liver and blood. These data were then used to compute liver ECV. 172 subjects were included in the study. Of these, 140 subjects were normal cardiac function patients, 16 were TOF repair patients and 16 patients were with Fontan palliation. A statistically significant difference in both the liver native T1 and ECV measurements was found between patients with normal cardiac function vs. Fontan palliation patients (p<0.01). Our data indicate that measuring T1 maps both pre- and post-GBCA injection within CMR scan session can be used to follow progression of liver fibrosis. This technique has the potential to improve diagnosis and treatment of patients with chronic liver disease and liver fibrosis.

Abstract 13421: Liver T1 Mapping MRI and Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Fatty liver disease and liver fibrosis are associated with cardiovascular disease (CVD) metabolic risk factors and events. However direct imaging of liver abnormalities using T1 mapping MRI in relation to CVD has not been investigated in large epidemiological cohorts. Hypothesis: Liver abnormalities (inflammation and/or fibrosis) by T1 mapping MRI are associated with CVD events. Methods: MESA enrolled 6814 participants free of clinical CVD at baseline, MESA1 (2000-2002). A subsample of participants underwent Modified Look-Locker T1 mapping MRI at the fifth follow-up exam, MESA5 (2010 -2012). T1 maps were analyzed avoiding vessels and biliary ducts, and pre- and post-contrast T1 times (25 minutes after injection) were calculated. Liver extracellular volume fraction (ECV) was calculated using the pre- and post-contrast T1 times of the liver and cardiac blood pool. Higher ECV and pre-contrast T1 time (PreT1) were indicative of liver abnormalities. Coronary heart disease (CHD), heart failure (HF) and atrial fibrillation (AF) events were ascertained between MESA 1 and MESA 5. Multivariable linear regression analysis evaluated the cross-sectional relationship between liver ECV and T1 time with cardiac events adjusted for ASCVD/AHA risk score, liver fat content by computed tomography, alcohol use, socioeconomic status and BMI. Results: In 888 participants (67.83±8 years, 51% female, 60% Caucasian, 4% Chinese, 26% African-American, 10% Hispanic) there were 63 cardiac events (44 CHD, 13 CHF and 18 AF) between MESA1 and 5. Compared to controls, PreT1 and ECV were significantly higher in those with any cardiac event and AF. In multivariable analysis, PreT1 (standardized β=0.08, p=0.018) and ECV (standardized β=0.09, p=0.008) were associated with composite cardiac events. Conclusion: Liver abnormalities (most likely inflammation and/or fibrosis) estimated by greater liver PreT1 and ECV, are associated with cardiac events in a multi-ethnic cohort.