Extracellular Volume Fraction Measurement Research Articles

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

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). 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). 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. 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.

Measurement of extracellular volume fraction using magnetic resonance-based conductivity tensor imaging.

Conductivity tensor imaging (CTI) using MRI is an advanced method that can non-invasively measure the electrical properties of living tissues. The contrast of CTI is based on underlying hypothesis about the proportionality between the mobility and diffusivity of ions and water molecules inside tissues. The experimental validation of CTI in both in vitro and in vivo settings is required as a reliable tool to assess tissue conditions. The changes in extracellular space can be indicators for disease progression, such as fibrosis, edema, and cell swelling. In this study, we conducted a phantom imaging experiment to test the feasibility of CTI for measuring the extracellular volume fraction in biological tissue. To mimic tissue conditions with different extracellular volume fractions, four chambers of giant vesicle suspension (GVS) with different vesicle densities were included in the phantom. The reconstructed CTI images of the phantom were compared with the separately-measured conductivity spectra of the four chambers using an impedance analyzer. Moreover, the values of the estimated extracellular volume fraction in each chamber were compared with those measured by a spectrophotometer. As the vesicle density increased, we found that the extracellular volume fraction, extracellular diffusion coefficient, and low-frequency conductivity decreased, while the intracellular diffusion coefficient slightly increased. On the other hand, the high-frequency conductivity could not clearly distinguish the four chambers. The extracellular volume fraction measured by the spectrophotometer and CTI method in each chamber were quite comparable, i.e., (1.00, 0.98 ± 0.01), (0.59, 0.63 ± 0.02), (0.40, 0.40 ± 0.05), and (0.16, 0.18 ± 0.02). The prominent factor influencing the low-frequency conductivity at different GVS densities was the extracellular volume fraction. Further studies are needed to validate the CTI method as a tool to measure the extracellular volume fractions in living tissues with different intracellular and extracellular compartments.

Measurement of extracellular volume fraction using magnetic resonance-based conductivity tensor imaging

Conductivity tensor imaging (CTI) using MRI is an advanced method that can non-invasively measure the electrical properties of living tissues. The contrast of CTI is based on underlying hypothesis about the proportionality between the mobility and diffusivity of ions and water molecules inside tissues. The experimental validation of CTI in both in vitro and in vivo settings is required as a reliable tool to assess tissue conditions. The changes in extracellular space can be indicators for disease progression, such as fibrosis, edema, and cell swelling. In this study, we conducted a phantom imaging experiment to test the feasibility of CTI for measuring the extracellular volume fraction in biological tissue. To mimic tissue conditions with different extracellular volume fractions, four chambers of giant vesicle suspension (GVS) with different vesicle densities were included in the phantom. The reconstructed CTI images of the phantom were compared with the separately-measured conductivity spectra of the four chambers using an impedance analyzer. Moreover, the values of the estimated extracellular volume fraction in each chamber were compared with those measured by a spectrophotometer. As the vesicle density increased, we found that the extracellular volume fraction, extracellular diffusion coefficient, and low-frequency conductivity decreased, while the intracellular diffusion coefficient slightly increased. On the other hand, the high-frequency conductivity could not clearly distinguish the four chambers. The extracellular volume fraction measured by the spectrophotometer and CTI method in each chamber were quite comparable, i.e., (1.00, 0.98 ± 0.01), (0.59, 0.63 ± 0.02), (0.40, 0.40 ± 0.05), and (0.16, 0.18 ± 0.02). The prominent factor influencing the low-frequency conductivity at different GVS densities was the extracellular volume fraction. Further studies are needed to validate the CTI method as a tool to measure the extracellular volume fractions in living tissues with different intracellular and extracellular compartments.

Feasibility of iodine concentration and extracellular volume fraction measurement derived from the equilibrium phase dual-energy CT for differentiating thymic epithelial tumors

PurposeTo assess the diagnostic feasibility of iodine concentration (IC) and extracellular volume (ECV) fraction measurement using the equilibrium phase dual-energy CT (DECT) for the evaluation of thymic epithelial tumors (TETs).Materials and methodsThis study included 33 TETs (11 low-risk thymomas, 11 high-risk thymomas, and 11 thymic carcinomas) that were assessed by pretreatment DECT. IC was measured during the equilibrium phases and ECV fraction was calculated using IC of the thymic lesion and the aorta. IC and ECV fraction were compared among TET subtypes using the Kruskal–Wallis H test and Mann–Whitney U test. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the ability of IC and ECV fraction to diagnose thymic carcinoma.ResultsIC during the equilibrium phase and ECV fraction differed among the three TET groups (both p < 0.001). IC during the equilibrium phase and ECV fraction was significantly higher in thymic carcinomas than in thymomas (1.9 mg/mL vs. 1.2 mg/mL, p < 0.001; 38.2% vs. 25.9%, p < 0.001; respectively). The optimal cutoff values of IC during the equilibrium phase and of ECV fraction to diagnose thymic carcinoma were 1.5 mg/mL (AUC, 0.955; sensitivity, 100%; specificity, 90.9%) and 26.8% (AUC, 0.888; sensitivity, 100%; specificity, 72.7%), respectively.ConclusionIC and ECV fraction measurement using DECT are helpful in diagnosing TETs. High IC during the equilibrium phase and high ECV fraction are suggestive of thymic carcinoma.

Diastolic Dysfunction Is Associated with Impaired Cardiopulmonary Exercise Performance in Sickle Cell Disease

▪Background:Left ventricular diastolic dysfunction is associated with increased mortality in sickle cell disease (SCD). Diffuse myocardial fibrosis is common in patients with SCD and is associated with diastolic dysfunction. Measurement of functional capacity by cardiopulmonary exercise test (CPET) has prognostic value in several cardiac diseases. Exercise impairment is common in SCD, but the causes and correlates are not well understood. Diastolic dysfunction is associated with a shorter 6-minute walk distance in SCD, but the effect of diastolic dysfunction and myocardial fibrosis on CPET has not been studied before.Methods:As part of a prospective study to characterize the cardiomyopathy of SCD (NCT02410811), children and adults with SCD underwent cardiac MRI (CMR), echocardiography and cycle ergometer CPET. Diffuse myocardial fibrosis was assessed by CMR-based measurement of extracellular volume fraction (ECV) from pre- and post-gadolinium T1 maps. Cardiac chamber sizes and cardiac performance were evaluated using CMR, and diastolic parameters were measured by echocardiography. Patients were classified to have diastolic dysfunction if they had left atrial enlargement and abnormalities in two diastolic parameters (E/e' ratio and e'). The following measures were recorded during CPET: percent predicted VO2 at maximum exercise (VO2 max) and ventilation efficiency (VE/VCO2 slope at maximum exercise (VE/VCO2 max). Reduced exercise capacity was defined by VO2 max <80% and classified as mild (VO2max 60-80%) or moderate to severe (VO2 max <60%).Results:Fifteen patients with SCD have completed the study (age range 8-38 years). No adverse events were reported within one month of CPET. Only one patient did not reach maximum exercise due to muscular fatigue. Fourteen patients (93%) had reduced exercise capacity; four of them (28%) had mild impairment and 10 (71%) had moderate to severe impairment. Four patients had diastolic dysfunction and none had systolic dysfunction. Patients with diastolic dysfunction had lower exercise capacity compared to patients with normal diastolic function as measured by lower VO2 max (46.6 ± 5.9% vs 59.2 ± 11.5%; p=0.02). The z-score of the left ventricular lateral E/e' ratio, a diastolic measure that reflects left ventricular filling pressure, negatively correlated with the maximal exercise capacity VO2 max (r=-0.57, p=0.02) and positively with worse ventilation efficiency measured by VE/VCO2 max (r=0.61, p=0.01), indicating an association between diastolic dysfunction and worse exercise performance. We did not find an association between ECV and exercise capacity. Hemoglobin concentration was moderately associated with VO2 max (r=0.37) but this association was not statistically significance (p=0.09).Conclusion:Diastolic dysfunction is associated with poor exercise capacity assessed by CPET in patients with SCD. Myocardial diastolic dysfunction may be one of the causes of impaired exercise capacity in SCD. Strategies to prevent or delay the acquisition of diastolic dysfunction to improve exercise capacity and long-term outcomes in SCD should be explored. DisclosuresQuinn:Global Blood Therapeutics: Research Funding.

Systolic modified Look-Locker inversion recovery myocardial T1 mapping improves the accuracy of T1 and extracellular volume fraction measurements of patients with high heart rate or atrial fibrillation.

Image data for T1 mapping are generally acquired during mid-diastole period. However, T1 mapping tends to fail for patients with high heart rate or atrial fibrillation because of short or irregular R-R interval. Focusing on the evidence that the timing of systole is more stable than that of diastole from the R wave, we compared systolic T1 mapping with conventional diastolic T1 mapping for all participants (n = 58) by visual scoring of T1 calculation error. The systolic scores were significantly better than the diastolic scores (p < 0.05). This advantage of the systolic scores was confirmed selectively for patients with atrial fibrillation (p < 0.05, n = 19). The successful number of nonrigid image registration alignment for extracellular volume fraction (ECV) analysis also increased significantly for systolic images compared with diastolic images (p < 0.05). Thus, systolic T1 mapping improves the accuracy of T1 values and ECV analysis.

Hepatic magnetic resonance T1-mapping and extracellular volume fraction compared to shear-wave elastography in pediatric Fontan-associated liver disease

BackgroundChildren with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. Reliable noninvasive monitoring techniques are lacking or under development.ObjectiveTo investigate surrogate indicators of hepatic fibrosis in adolescents with Fontan circulation by evaluating hepatic magnetic resonance (MR) T1 mapping and extracellular volume fraction measurements compared to US shear-wave elastography.Materials and methodsWe analyzed hepatic native T1 times and extracellular volume fractions with modified Look-Locker inversion recovery. Liver stiffness was analyzed with shear-wave elastography. We compared results between 45 pediatric patients ages 16.7±0.6 years with Fontan circulation and 15 healthy controls ages 19.2±1.2 years. Measurements were correlated to clinical and hemodynamic data from cardiac catheterization.ResultsMR mapping was successful in 35/45 patients, revealing higher hepatic T1 times (774±44 ms) than in controls (632±52 ms; P<0.001) and higher extracellular volume fractions (47.4±5.0%) than in controls (34.6±3.8%; P<0.001). Liver stiffness was 1.91±0.13 m/s in patients vs. 1.20±0.10 m/s in controls (P<0.001). Native T1 times correlated with central venous pressures (r=0.5, P=0.007). Native T1 was not correlated with elastography in patients (r=0.2, P=0.1) or controls (r = −0.3, P=0.3). Extracellular volume fraction was correlated with elastography in patients (r=0.5, P=0.005) but not in controls (r=0.2, P=0.6).ConclusionIncreased hepatic MR relaxometry and shear-wave elastography values in adolescents with Fontan circulation suggested the presence of hepatic fibrosis or congestion. Central venous pressure was related to T1 times. Changes were detected differently with MR relaxometry and elastography; thus, these techniques should not be used interchangeably in monitoring hepatic fibrosis.

Extracellular volume fraction measurement correlates with lymphocyte abundance in thymic epithelial tumors

BackgroundRecent advance in tissue characterization with parametric mapping imaging has the potential to be a novel biomarker for histopathologic correlation with thymic epithelial tumors (TETs). The purpose of our study is to evaluate MRI T1 mapping with the calculation of extracellular volume (ECV) fraction for histologic correlation with thymic epithelial tumor based on lymphocyte abundance.MethodsA retrospective study including 31 consecutive patients (14 men and 17 women, median age, 56 years; interquartile range, 12 years) with TETs was performed. The T1 values and ECV were assessed by using quantitative MRI mapping techniques. Mann-Whitney U test, Kruskal-Wallis H test, and receiver operating characteristic curve analyses were used to assess discrimination between different types of TETs based on lymphocyte abundance.ResultsExtracellular volume was significantly higher in TETs with sparse lymphocyte, including type A, type B3, and thymic carcinoma, compared with those with abundant lymphocyte, including type B1, B2, and AB thymomas (42.5% vs 26.9%, respectively; p < 0.001). Extracellular volume was significantly higher in thymic carcinoma compared with low grade and high grade thymomas (48.6% vs 31.1% vs 27.6%, respectively; p = 0.002).ConclusionsT1 mapping with the calculation of extracellular volume (ECV) fraction correlate with the WHO histologic classification of thymic epithelial tumor based on lymphocyte abundance.

Myocardial extracellular volume fraction measurements with MOLLI 5(3)3 by cardiovascular MRI for the discrimination of healthy volunteers from dilated and hypertrophic cardiomyopathy patients

To investigate the diagnostic performance of myocardial native T1 time and the extracellular volume fraction (ECV) for differentiating dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) patients from healthy volunteers. Forty healthy volunteers, 57 DCM patients, and 30 HCM patients were enrolled, all of whom underwent cardiovascular magnetic resonance imaging (CMRI), including late gadolinium enhancement (LGE) and native and post-contrast T1 mapping acquired with the modified Look-Locker inversion recovery (MOLLI) sequence on a 1.5 T MRI system. ECV were calculated by native and post-contrast T1 times. Multivariate binary logistic regression analyses and receiver operating characteristic (ROC) curve analyses were used to assess the concordance with the clinical diagnosis of DCM and HCM. DCM and HCM patients had significantly higher myocardial native T1 times and ECVs than healthy volunteers (p<0.001). Multivariate logistic regression analyses showed that ECV was an independent predictor of DCM and HCM diagnosis (OR=1.556, p<0.001 and OR=1.847, p=0.001, respectively). ROC curve analysis indicated that ECV provided greater distinction between DCM patients and healthy volunteers than native T1 time (AUC: 0.889 versus 0.780, p=0.021). At the optimal cut-off value, ECV identified DCM and HCM patients with 80.7% and 83.3% sensitivity, 87.5% and 70% specificity, 90.2% and 67.6% positive predictive value, and 76.1% and 84.8% negative predictive value, respectively. The increased ECV in DCM and HCM patients reflects myocardial extracellular matrix expansion. Myocardial ECV provides good diagnostic performance for identifying DCM and HCM patients from healthy volunteers.

Role of Cardiac Computed Tomography in the Diagnosis of Left Ventricular Myocardial Diseases.

Multimodality imaging is indicated for the evaluation of left ventricular (LV) myocardial diseases. Cardiac magnetic resonance (CMR) allows morphological and functional assessment of the LV along with soft tissue characterization. Technological advances in cardiac computed tomography (CT) have led to the development of techniques for diagnostic acquisition in LV myocardial disease. Cardiac CT facilitates the characterization of LV myocardial disease based on anatomy, function, and enhancement pattern. LV regional and global functional parameters are evaluated using multi-phasic cine CT images. CT myocardial perfusion facilitates the identification of hemodynamically significant coronary artery stenosis. Cardiac CT with delayed enhancement is used to detect myocardial scarring or fibrosis in myocardial infarction and non-ischemic cardiomyopathy, and for the measurement of extracellular volume fraction in non-ischemic cardiomyopathy. In this review, we review imaging techniques and key imaging features of cardiac CT used for the evaluation of myocardial diseases, along with CMR findings.

Blood T1* correction increases accuracy of extracellular volume measurements using 3T cardiovascular magnetic resonance: Comparison of T1 and T1* maps

The goals were to compare the differences between ECVL (extracellular volume derived from myocardial T1 and blood T1), ECVc (combination of myocardial T1 and blood T1*), and ECVnL (derived from myocardium T1* and blood T1*), and to explore the diagnostic accuracy of these factors for discriminating between controls and patients. The Modified Look-Locker Inversion Recovery sequence was performed in 42 subjects to generate both T1 and T1* maps. Native and post-contrast T1 values for myocardium and blood pool were obtained, and ECVL, ECVc, and ECVnL were then calculated. The global ECVc values were smaller than the ECVL values (0.006, 2.11%, p < 0.001) and larger than the ECVnL values (0.06, 21.6%, p < 0.001) in all participants. The ECVc led to a 4–6% increase in the AUC value and a 24–32% reduction in the sample size to differentiate between the controls and other patients when compared with the ECVL. Blood T1* correction can improve the precision of blood T1 values and can consequently increase the accuracy of the extracellular volume fraction measurement. The ECVc can be used to improve diagnostic accuracy and reduce the sample size required for a clinical study.

Extracellular volume fraction measurements derived from the longitudinal relaxation of blood-based synthetic hematocrit may lead to clinical errors in 3\xa0T cardiovascular magnetic resonance

BackgroundThe extracellular volume (ECV), derived from cardiovascular magnetic resonance (CMR) T1 mapping, is a biomarker of the extracellular space in the myocardium. The hematocrit (HCT), measured from venipuncture, is required for ECV measurement. We test the clinic values of synthetic ECV, which is derived from the longitudinal relaxation of blood–based (T1blood) synthetic hematocrit in 3 T CMR.MethodsA total of 226 subjects with CMR T1 mapping and HCT measurement taken on the same day as the CMR were retrospectively enrolled and randomly split into derivation (n = 121) and validation (n = 105) groups, comprising healthy subjects (n = 45), type 2 diabetes mellitus (T2DM) patients (n = 60), hypertrophic cardiomyopathy (HCM) patients (n = 93), and 28 other patients. Correlation of T1blood with the measured HCT (HCTm) was established in the derivation group and used in both the derivation and the validation groups. The relationships between the ECV values derived from both the synthetic HCT (HCTsyn) and HCTm were explored. In addition, the differences in the ECV values among the HC, T2DMs, and HCMs were compared.ResultsRegression between the HCTm and 1/T1blood was linear (R2 = 0.19, p < 0.001), and the regression equation was: HCTsyn = [561.6*(1/T1blood)] + 0.098 in the derivation group. The measured ECV (ECVm) was strongly correlated with the synthetic ECV (ECVsyn) (R2 = 0.87, p < 0.001) and mildly correlated with the difference between the ECVsyn and ECVm (R2 = 0.10, p < 0.001) in the derivation group. Also in this group, the ECVm was larger in T2DMs than that in healthy cohort (29.1 ± 3.1% vs. 26.4 ± 2.4%, p = 0.002), whereas, the ECVsyn did not differ between T2DMs and healthy cohort (28.3 ± 2.9% vs. 26.9 ± 2.2%, p = 0.064). Compared with the healthy cohort, the HCMs were associated with higher ECVsyn and ECVm of the mid-ventricle in both the derivation and the validation groups. Using our center’s normal cut-off of 31.8%, the use of ECVsyn would lead to a 6–25% incorrect categorization of patients in the derivation and validation groups.ConclusionsECVsyn derived from HCTsyn may lead to clinical errors in 3 T CMR, especially for patients who have only a subtle elevation in ECV.

Measurement of liver and spleen interstitial volume in patients with systemic amyloid light-chain amyloidosis using equilibrium contrast CT.

To investigate equilibrium contrast-enhanced CT (EQ-CT) measurement of extracellular volume fraction (ECV) in patients with systemic amyloid light-chain (AL) amyloidosis, testing the hypothesis that ECV becomes elevated in the liver and spleen and ECV correlates with other estimates of organ amyloid burden. 26 patients with AL amyloidosis underwent EQ-CT, and ECV was measured in the liver and spleen. Patients also underwent serum amyloid P (SAP) component scintigraphy with grading of liver and spleen involvement. Mann-Whitney U test was used to test for a difference between patients with amyloid deposition (SAP grade 1-3) and those without (SAP grade 0). Variation in ECV across SAP grades was assessed using the Kruskal-Wallis test and association between ECV and SAP grades with Spearman correlation. Mean ECV in the spleen and liver was significantly greater (p<0.0005) in amyloidotic organs (SAP grade 1-3) [spleen, liver: 0.430, 0.375] compared with healthy tissues [spleen, liver: 0.304, 0.269]. ECV increased with increasing amyloid burden, showing positive correlation with SAP grade in both the liver (r=0.758) and spleen (r=0.867). In patients with systemic AL amyloidosis, EQ-CT can demonstrate increased spleen and liver ECV, which is associated with amyloid disease burden.

Synthetic hematocrit derived from the longitudinal relaxation of blood can lead to clinically significant errors in measurement of extracellular volume fraction in pediatric and young adult patients

BackgroundExtracellular volume fraction (ECV) is altered in pathological cardiac remodeling and predicts death and arrhythmia. ECV can be quantified using cardiovascular magnetic resonance (CMR) T1 mapping but calculation requires a measured hematocrit (Hct). The longitudinal relaxation of blood has been used in adults to generate a synthetic Hct (estimate of true Hct) but has not been validated in pediatric populations.MethodsOne hundred fourteen children and young adults underwent a total of 163 CMRs with T1 mapping. The majority of subjects had a measured Hct the same day (N = 146). Native and post-contrast T1 were determined in blood pool, septum, and free wall of mid-LV, avoiding areas of late gadolinium enhancement. Synthetic Hct and ECV were calculated and intraclass correlation coefficient (ICC) and linear regression were used to compare measured and synthetic values.ResultsThe mean age was 16.4 ± 6.4 years and mean left ventricular ejection fraction was 59% ± 9%. The mean measured Hct was 41.8 ± 3.0% compared to the mean synthetic Hct of 43.2% ± 2.9% (p < 0.001, ICC 0.46 [0.27, 0.52]) with the previously published model and 41.8% ± 1.4% (p < 0.001, ICC 0.28 [0.13, 0. 42]) with the locally-derived model. Mean measured mid-free wall ECV was 30.5% ± 4.8% and mean synthetic mid-free wall ECV of local model was 29.7% ± 4.6% (p < 0.001, ICC 0.93 [0.91, 0.95]). Correlations were not affected by heart rate and did not significantly differ in subpopulation analysis. While the ICC was strong, differences between measured and synthetic ECV ranged from −8.4% to 4.3% in the septum and −12.6% to 15.8% in the free wall. Using our laboratory’s normal cut-off of 28.5%, 59 patients (37%) were miscategorized (53 false negatives, 6 false positives) with published model ECV. The local model had 37 miscategorizations (20 false negatives, 17 false positives), significantly fewer but still a substantial number (23%).ConclusionsOur data suggest that use of synthetic Hct for the calculation of ECV results in miscategorization of individual patients. This difference may be less significant once synthetic ECV is calculated and averaged over a large research cohort, making it potentially useful as a research tool. However, we recommend formal measurement of Hct in children and young adults for clinical CMRs.

Abstract 12505: Prognostic Significance of Myocardial Extracellular Volume Fraction

Background: Cardiac magnetic resonance (CMR) techniques permit quantification of cardiac extracellular volume fraction (ECV), inclusive of interstitial fibrosis. ECV and late gadolinium enhancement (LGE), suggestive of cardiac replacement fibrosis, have been independently linked with heart failure (HF) events. Non-coronary artery disease type LGE has not been excluded in ECV measures. We examined associations between ECV censored for LGE-involved segments, LGE presence, and HF events. Methods: Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured &gt;30%, the upper 95% bounds of a healthy group without known cardiac disease (n=28). Patients were divided into 4 groups based on presence of elevated ECV and of any LGE. Subsequent HF admission and any death were ascertained. Their relationship with ECV was examined separately and as a composite with Cox proportional hazard models. Results: Of 1,604 serial patients with T1 maps, 1,047 were eligible after exclusions and followed over a median 10.5 (interquartile range 5.4, 21.4) months. Patients with elevated ECV had an increased risk for death (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.78 to 3.79)), HF admissions (HR 1.97, 95% CI 1.48 to 2.61), and combined endpoint (HR 2.14, 95% CI 1.69 to 2.70) regardless of LGE presence (Table). After adjustments for covariates, the relationship persisted for death (HR 1.86, 95% CI 1.24 to 2.79), hospitalization (HR 1.54, 95% CI 1.13 to 2.10), and combined endpoints (HR 1.60, 95% CI 1.24 to 2.07). Conclusion: Extracellular volume fraction measures were associated with heart failure outcomes, despite censoring of replacement fibrosis segments and even among patients without any replacement fibrosis. ECV may have a synergistic role with replacement fibrosis in heart failure risk assessment.

Native T1 mapping and extracellular volume fraction measurement for assessment of right ventricular insertion point and septal fibrosis in chronic thromboembolic pulmonary hypertension.

The aim of this study was to assess septal and right ventricular insertion point (RVIP) fibrosis in patients with chronic thromboembolic pulmonary hypertension (CTEPH) via native T1 mapping and extracellular volume fraction (ECV) determination and to analyze correlations with functional parameters. Imaging was performed at 1.5 Tesla in 24 patients diagnosed with CTEPH and 24 controls. T1 values were measured within the septal myocardium, the upper and lower RVIP, and the lateral wall at basal short axis section. The mean septal native T1 values were 1012.8ms ± 50.5 in the CTEPH group and 956.9ms ± 24.4 in controls (p < 0.001), upper RIVP 1050.8ms ± 64.2 vs. 965.3ms ± 37.1 (p < 0.001), and lower RVIP 1084.4ms ± 93.1 vs. 959.8ms ± 40.4 (p < 0.001). The corresponding mean ECV values were also significantly increased in the CTEPH group (p < 0.001). Native septal T1 showed a strong negative correlation with right ventricular ejection fraction (k = -0.92; p = 0.01). We conclude that native T1 mapping and ECV assessment enable visualization and quantification of septal fibrosis in CTEPH patients. The results also correlate well with right ventricular ejection fraction. Therefore, these parameters might be useful for prognosis and as therapy-monitoring tool in the future. • Septal native T1 and ECV values are significantly higher in CTEPH patients. • Native T1 and ECV values are elevated even in absence of LGE. • These techniques therefore enable an improved quantification of septal fibrosis in CTEPH. • Native T1 values also correlate well with right ventricular EF and PA-pressure. • Prognosis and therapy-monitoring might be assessable in the future with these parameters.

Myocardial extracellular volume fraction measurement in chronic total coronary occlusion: Association with myocardial injury, angiographic collateral flow, and functional recovery

To investigate whether myocardial extracellular volume fraction (ECV) measurement by cardiac MR is indicative of myocardial injury, angiographic collateral flow, and functional recovery in patients with chronic total coronary occlusion (CTO). A total of 50 CTO patients undergoing 1.5 Tesla MR were prospectively enrolled, and 28 underwent a second MR 6 months after revascularization. T1-mapping based indices, including pre- and postcontrast T1 values and ECV, were obtained from infarcted and non-infarcted myocardium, myocardial segments, and coronary territory. The severity of myocardial injury was rated by transmurality extent of infarction (TEI) and regional wall motion abnormalities (RWMA) score. Angiographic collateral flow was evaluated using Rentrop classification. Improvement in segmental wall motion at 6 months was also assessed. ECV and postcontrast T1 value significantly outperformed precontrast T1 value for identifying myocardial infarction (area under the receiver operating characteristic curve [AUC]: 0.998 and 0.953 versus 0.824, all P < 0.02). Myocardial ECV was strongly correlated with TEI (P = 0.000), RWMA score (P = 0.000), and collateral classification (P = 0.007 for left anterior descending artery [LAD] territory, P = 0.001 for non-LAD territory). Furthermore, the likelihood of functional recovery was better predicted by ECV than by late gadolinium enhancement (LGE) (AUC: 0.76 versus 0.68, P < 0.02). Myocardial ECV may be a useful surrogate to assess myocardial injury and angiographic collateral flow in CTO, and ECV provides incremental value to LGE in assessing functional recovery after revascularization. J. MAGN. RESON. IMAGING 2016;44:972-982.

Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence.

BackgroundMyocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.ObjectiveTo goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.MethodsC57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.ResultsDetailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

Myocardial T1 and extracellular volume fraction measurement in asymptomatic patients with aortic stenosis: reproducibility and comparison with age-matched controls

(i) To establish the test-retest reproducibility of myocardial T1 and extracellular volume (ECV) fraction measurement in asymptomatic patients with moderate-severe aortic stenosis (AS), (ii) to compare reproducibility using motion-corrected (MOCO) parametric T1 maps for analysis vs. full MOLLI series of images, and (iii) to compare T1 and ECV between patients and age-matched controls. 3 T cardiac MRI was performed twice on 10 patients (median interval 7 days) to assess reproducibility. An additional 40 patients and 22 asymptomatic controls underwent a single MRI. Native T1 and ECV were calculated by outlining the myocardium on T1 maps generated inline, and using an offline T1 fit on the MOCO multiple inversion-time raw image series, in the reproducibility cohort (n = 10). Reproducibility was excellent using the inline T1 maps (CoVs for T1: 1.77%; ECV: 6.52%) and good using the full MOLLI series (CoVs for T1: 8.52%; ECV: 12.98%). On comparing AS and controls, who were well matched for age, gender and co-morbidities, there was no significant difference in the native T1 or ECV (T1 = 1103.32 ± 33.07 vs. 1092.27 ± 34.29; ECV = 0.243 ± 0.019 vs. 0.251 ± 0.026 in patients and controls, P > 0.05), which was maintained even after splitting the patients into moderate and severe AS subgroups. The test-retest reproducibility of myocardial T1 quantification using MOLLI is excellent in patients with AS and is highest using inline generated T1 maps for analysis. There was no difference in native myocardial T1 or ECV between asymptomatic patients with moderate-severe AS and age-matched controls without valve disease.

Temporal stability of gel relaxation-time phantoms for quality control of T1 and extracellular volume fraction measurements

Background Quantification of interstitial fibrosis by T1-mapping continues to gather momentum clinically with the recognition that extracellular volume fraction (ECV) measurements are pathologically elevated in a range of conditions. Well-known dependence of ECV estimation on imaging parameters requires quality-control by T1 phantoms[1-3]. These typically comprise agarose with NiCl[2] doping,[4] and are often used short-term, but with limited long-term data[5]. Such phantoms might assure long-term stability (over years) of methods applied in patients eg against scanner alterations. We therefore sought to assess their long-term T1 and T2 stability.