Global Myocardial Extracellular Volume Research Articles

Increase in skeletal muscle extracellular volume as an under-recognised change detected at cardiac MRI in hypertrophic cardiomyopathy

To explore skeletal muscle change and its correlation with the myocardium in hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance imaging (cMRI) with T1 mapping and late gadolinium enhancement (LGE). This retrospective study enrolled 50 HCM patients and 35 healthy controls. The extracellular volume (ECV) of the skeletal muscle and myocardium, the presence and absence of LGE of the myocardium, and cardiac troponin T (cTnT), were assessed. In the HCM group, the elevated ECVskeletal group was defined as ECVskeletal >2 standard deviations (SD) above the mean value of the controls. Statistical analyses included Student's t-test, the Mann-Whitney U-test, and linear regression. ECVskeletal in the HCM group was higher than in the control group (mean 13.0 versus 10.9%; p<0.001), with 20 (40%) HCM patients having elevated ECVskeletal (ECVskeletal ≥13.7%). In the HCM group, ECVskeletal had a positive linear correlation with global myocardial ECV (r=0.37, p=0.009). In addition, the elevated ECVskeletal group had a higher cTnT than the non-elevated group (log cTnT, mean 1.55 versus 1.16, p=0.045). Furthermore, segmental myocardial ECV in the elevated ECVskeletal group was higher than in the non-elevated group, despite the presence or absence of myocardial LGE (median 30.1 versus 27.2%; 26.5 versus 24.6%, both p<0.001) or hypertrophy (median 29.0 versus 26.0%; 26.8 versus 24.8%, both p<0.001). In the HCM patients, ECVskeletal was higher than in the healthy controls. Furthermore, some ECVskeletal changes had corresponding changes in the cTnT and myocardium.

T1-Mapping and extracellular volume estimates in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T

BackgroundCardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD)—a fatal X-linked genetic disorder. Late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling, but it is often a late finding. Current research aims to investigate cardiovascular magnetic resonance (CMR) biomarkers, including native (pre-contrast) T1 and extracellular volume (ECV) to evaluate the early on-set of microstructural remodeling and to grade disease severity. To date, native T1 measurements in DMD have been reported predominantly at 1.5T. This study uses 3T CMR: (1) to characterize global and regional myocardial pre-contrast T1 differences between healthy controls and LGE + and LGE− boys with DMD; and (2) to report global and regional myocardial post-contrast T1 values and myocardial ECV estimates in boys with DMD, and (3) to identify left ventricular (LV) T1-mapping biomarkers capable of distinguishing between healthy controls and boys with DMD and detecting LGE status in DMD.MethodsBoys with DMD (N = 28, 13.2 ± 3.1 years) and healthy age-matched boys (N = 20, 13.4 ± 3.1 years) were prospectively enrolled and underwent a 3T CMR exam including standard functional imaging and T1 mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Pre-contrast T1 mapping was performed on all boys, but contrast was administered only to boys with DMD for post-contrast T1 and ECV mapping. Global and segmental myocardial regions of interest were contoured on mid LV T1 and ECV maps. ROI measurements were compared for pre-contrast myocardial T1 between boys with DMD and healthy controls, and for post-contrast myocardial T1 and ECV between LGE + and LGE− boys with DMD using a Wilcoxon rank-sum test. Results are reported as median and interquartile range (IQR). p-Values < 0.05 were considered significant. Receiver Operating Characteristic analysis was used to evaluate a binomial logistic classifier incorporating T1 mapping and LV function parameters in the tasks of distinguishing between healthy controls and boys with DMD, and detecting LGE status in DMD. The area under the curve is reported.ResultsBoys with DMD had significantly increased global native T1 [1332 (60) ms vs. 1289 (56) ms; p = 0.004] and increased within-slice standard deviation (SD) [100 (57) ms vs. 74 (27) ms; p = 0.001] compared to healthy controls. LGE− boys with DMD also demonstrated significantly increased lateral wall native T1 [1322 (68) ms vs. 1277 (58) ms; p = 0.001] compared to healthy controls. LGE + boys with DMD had decreased global myocardial post-contrast T1 [565 (113) ms vs 635 (126) ms; p = 0.04] and increased global myocardial ECV [32 (8) % vs. 28 (4) %; p = 0.02] compared to LGE− boys. In all classification tasks, T1-mapping biomarkers outperformed a conventional biomarker, LV ejection fraction. ECV was the best performing biomarker in the task of predicting LGE status (AUC = 0.95).ConclusionsBoys with DMD exhibit elevated native T1 compared to healthy, sex- and age-matched controls, even in the absence of LGE. Post-contrast T1 and ECV estimates from 3T CMR are also reported here for pediatric patients with DMD for the first time and can distinguish between LGE + from LGE− boys. In all classification tasks, T1-mapping biomarkers outperform a conventional biomarker, LVEF.

Age and Gender Impact the Measurement of Myocardial Interstitial Fibrosis in a Healthy Adult Chinese Population: A Cardiac Magnetic Resonance Study.

Background: Diffuse myocardial fibrosis is a common pathological process in many cardiovascular diseases. In order to determine disease, we must have standard normal imaging values. We investigated myocardial interstitial fibrosis of the left ventricle (LV) in a healthy population of Chinese adults and explored the impact of gender, age, and other physiological factors using a T1 mapping technique of cardiac magnetic resonance imaging (CMR).Materials and Methods: We recruited 69 healthy adult Chinese subjects (35 males; age 18–76). LV function and global strain were obtained from functional imaging. T1 mapping was performed using a modified look-locker sequence. Global and segmental native T1 and extracellular volume (ECV) were calculated using dedicated software. Gender, age, and segmental variation of both native myocardial T1 and ECV of the LV were analyzed.Results: The global myocardial native T1 and ECV of the LV in this Chinese adult healthy population was 1,202 ± 45 ms and 27 ± 3% at 3T field strength, respectively. Females had a higher myocardial native T1 and ECV of the LV compared to males [1,210 (1,188–1,264) ms vs. 1,182 (1,150–1,211) ms, P < 0.001; 28 ± 3 vs. 26 ± 3%, P = 0.027, respectively]. ECV in older group was higher than younger group [27 (26–29)% vs. 25 (24–29), P = 0.019]. The multi-variate linear regression analysis showed that only gender (Beta = −0.512, P < 0.001) was independently related with global native T1 of LV while gender (Beta = −0.278, P = 0.017) and age (Beta = 0.303, P = 0.010) were independently related with global ECV of LV. From the base to apex of the LV, myocardial native T1 (P = 0.020) and ECV (P < 0.001) significantly increased. Within the same slice of the LV, there were significant segmental variations of both myocardial native T1 (P < 0.001) and ECV (P < 0.001) values.Conclusion: Gender and age have significant impacts on the imaging markers of myocardial interstitial fibrosis in healthy adult Chinese volunteers. Segmental variation of myocardial interstitial fibrosis was also observed.

Association between myocardial extracellular volume and strain analysis through cardiovascular magnetic resonance with histological myocardial fibrosis in patients awaiting heart transplantation

BackgroundCardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) and tissue tracking strain analyses are proposed as non-invasive methods for quantifying myocardial fibrosis and deformation. This study sought (1) to histologically validate myocardial ECV against the collagen volume fraction (CVF) measured from tissue samples of patients undergoing heart transplantation and (2) to detect the correlations between myocardial systolic strain and the myocardial ECV and histological CVF in patients undergoing heart transplantation.MethodsA total of 12 dilated cardiomyopathy (DCM) and 10 ischaemic cardiomyopathy (ICM) patients underwent T1 mapping with the Modified Look Locker Inversion recovery (MOLLI) sequence, T2 mapping and ECV. Myocardial systolic strain, including left ventricular global longitudinal (GLS), circumferential (GCS) and radial strain (GRS), were quantified using CMR cine images with tissue tracking analysis software. Tissue samples were collected from each of 16 segments of the explanted hearts and were stained with picrosirius red for histological CVF quantification.ResultsA strong relationship was observed between the global myocardial ECV and histological CVF in the DCM and ICM patients based on a per-patient analysis (r = 0.904 and r = 0.901, respectively, p < 0.001). In the linear mixed-effects regression analysis, ECV correlated well with the histological CVF in the DCM and ICM patients on a per-segment basis (β = 0.838 and β = 0.915, respectively, p < 0.001). In the multivariate linear regression analysis, histological CVF was the strongest independent determinant of ECV in the patients awaiting heart transplantation (standardised β = 0.860, p < 0.001). However, the T2 time, GLS, GCS and GRS showed no significant associations with ECV and CVF in the patients awaiting heart transplantation.ConclusionsECV derived from CMR correlated well with histological CVF, indicating its potential as a non-invasive tool for the quantification of myocardial fibrosis. Additionally, impaired myocardial systolic strains were not associated with the ECV and CVF in the patients awaiting heart transplantation.

Elevated Myocardial Extracellular Volume Fraction in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic, X-linked recessive disease with an associated cardiomyopathy characterized by myocardial fibrosis leading to heart failure, arrhythmias, and death. Earlier detection and treatment of cardiac involvement in DMD hold potential to improve outcomes. Cardiovascular magnetic resonance (CMR) extracellular volume (ECV) quantification using T1 mapping is a histologically validated, non-invasive marker of diffuse fibrosis. This study aims to determine the ECV in a pediatric DMD population, and correlate it with metrics of left ventricular function. A retrospective review of pediatric DMD subjects who underwent CMR at a single institution. A total of 47 DMD patients (mean age 14±2years) were included for analysis. Global myocardial ECV was significantly higher in the DMD group (29±6%) compared with published normal values (24±2%, p=0.0001). Higher ECV values correlate with indices of left ventricular function, including decreased left ventricular ejection fraction (r=-0.46, p=0.001) and indexed left ventricular end diastolic volume (r=0.41, p=0.004). ECV was not significantly higher in DMD patients with late gadolinium enhancement (LGE) (30±7%) compared to DMD patients without LGE (27±5%, p=0.0717). CMR T1 mapping is a feasible method for quantification of ECV in patients with DMD. Global myocardial ECV is significantly higher in the DMD population compared to healthy controls and correlates with other metrics of myocardial function. Global myocardial ECV may serve as an important tool to determine cardiac involvement in DMD population and help guide medical management.

Asymptomatic Cocaine Abuse - Myocardial Tissue Characterization Using Cardiac Biomarkers and Cardiovascular Magnetic Resonance Imaging.

Use of cocaine is widespread and associated with several cardiovascular diseases. Recent CMR studies indicate frequent myocardial scar/fibrosis in asymptomatic cocaine abusers (CA).Methods and Results:This study used a combination of advanced CMR tissue characterization techniques, including late gadolinium enhancement (LGE) for focal, and extracellular volume (ECV) imaging for diffuse myocardial injury/fibrosis, with circulating biomarkers for a comprehensive characterization of myocardial injury. We included 20 cardiac asymptomatic CA and a control group of 20 healthy volunteers. The comprehensive assessment included physical examination, resting ECG, exercise ECG, cardiac biomarkers, transthoracic echocardiogram and CMR. We did not find significant differences between CA and controls either in functional CMR parameters such as LVEDVi, LVESVi, LVEF, LV mass index, or in global myocardial ECV. Neither CA nor controls had evidence of myocardial edema on T2-weighted CMR, but 8 CA (40%), and none of the controls had focal myocardial scar (P<0.01). Interestingly, CA with focal myocardial scar on LGE had significantly higher high-sensitivity troponin I (hs-TNI) compared with CA without focal scar (median, 1.7 ng/L; IQR, 1.3-2.5 ng/L vs. 0.6 ng/L; 0.4-1.3 ng/L; P<0.01). Focal myocardial injury in terms of subtle LGE in 40% of asymptomatic CA was associated with higher hs-TNI. Comprehensive assessment including advanced ECV imaging indicates a focal rather than diffuse pattern of myocardial involvement in asymptomatic CA.

Comparison of short and long axis T1 and ECV maps in patients with myocarditis

Background T1 mapping and ECV imaging are promising diagnostic tools in patients with suspected myocarditis. However, there are currently no data on the potential influence of slice orientation on the derived T1 and ECV values. Thus, we compared global myocardial T1 and ECV values between slices with short and long axis orientation. Methods This study included 50 patients with clinically suspected myocarditis, who underwent CMR at 1.5 Tesla. T1 quantification was performed on three short (basis, center, apex) and on three long axis slices (2-, 3- and 4-chamber orientation), respectively. The modified Look-Locker inversionrecovery (MOLLI) sequence was used before and 15 minutes after administration of 0.075 mmol/kg GadoliniumBOPTA. Native T1, post-contrast T1 and extracellular volume (ECV) maps were calculated using a dedicated plug-in written for the OsiriX software. Mean native and post-contrast T1 as well as ECV were obtained from the three short and long axes, respectively. Results There were significantly lower median native myocardial T1 values on long axis slices (1079 (1040-1130.0)) compared to short axis slices (1103 (1069-1140); p=0.0026). However, there were no significant differences in postcontrast myocardial T1 values (median 554 (505-596) vs. 555 (509-601); p=0.2299) or ECV (median 30 (27-33) vs. 29 (26-33); p=0.6063) between short and long axis slices, respectively. Conclusions Slice orientation could be a potential confounding factor for the assessment of native global myocardial T1 values in myocarditis. Possible explanations for this finding include technical issues, such as variations in throughplane motion or partial-volume effects related to slice orientation, but also the heterogeneity of myocardial injury in myocarditis. However, our data indicate that global myocardial ECV values could be less sensitive to slice orientation.

CMR in Patients With Severe Myocarditis: Diagnostic Value of Quantitative Tissue Markers Including Extracellular Volume Imaging

ObjectivesThis study evaluated the accuracy of T2, T1, and extracellular volume (ECV) quantification as novel quantitative tissue markers in comparison with standard “Lake-Louise” cardiac magnetic resonance (CMR) criteria to diagnose myocarditis. BackgroundNovel approaches using T2 and T1 mapping may overcome the limitations of signal intensity-based parameters, which would potentially result in a better diagnostic accuracy compared with standard CMR techniques in suspected myocarditis. MethodsCMR was performed in 104 patients with myocarditis and 21 control subjects at 1.5-T. Patients with myocarditis underwent CMR 2 weeks (interquartile range: 1 to 7 weeks) after presentation with new-onset heart failure (n = 66) or acute chest pain (n = 38). T2 and T1 mapping were implemented into a standard protocol including T2-weighted (T2w), early gadolinium enhancement (EGE) CMR, and late gadolinium enhancement (LGE) CMR. T2 quantification was performed using a free-breathing, navigator-gated multiecho sequence. T1 quantification was performed using the modified Look-Locker inversion recovery sequence before and after administration of 0.075 mmol/kg gadobenate dimeglumine. T2, T1, and ECV maps were generated using a plug-in for the OsiriX software (Pixmeo, Bernex, Switzerland) to calculate mean global myocardial T2, T1, and ECV values. ResultsThe diagnostic accuracies of conventional CMR were 70% (95% confidence interval [CI]: 61% to 77%) for T2w CMR, 59% (95% CI: 56% to 73%) for EGE, and 67% (95% CI: 59% to 75%) for LGE. The diagnostic accuracies of mapping techniques were 63% (95% CI: 53% to 73%) for myocardial T2, 69% (95% CI: 60% to 76%) for native myocardial T1, and 76% (95% CI: 68% to 82%) for global myocardial ECV. The diagnostic accuracy of CMR was significantly improved to 90% (95% CI: 84% to 95%) by a stepwise approach, using the presence of LGE and myocardial ECV ≥27% as diagnostic criteria, compared with 79% (95% CI: 71% to 85%; p = 0.0043) for the Lake-Louise criteria. ConclusionsIn patients with clinical evidence for subacute, severe myocarditis, ECV quantification with LGE imaging significantly improved the diagnostic accuracy of CMR compared with standard Lake-Louise criteria.

Myocardial injury and fibrogenesis: extracellular volume expansion is associated with elevated Galectin-3 levels in patients with myocarditis

Background Myocarditis subsumes a variety of entities, including diverse courses from complete healing to dilated cardiomyopathy with severe myocardial fibrosis. T1-mapping cardiovascular magnetic resonance (CMR) has the ability to quantify myocardial extracellular volume (ECV) as a surrogate of acute and chronic myocardial injury. Galectin-3 is an important mediator of fibrogenesis and contributes to adverse left ventricular (LV) remodeling. This study evaluated, if myocardial ECV expansion is linked to Galectin-3 levels in patients with myocarditis. Methods Galectin-3 blood levels were measured in 20 patients with myocarditis using a commercially available chemiluminescent microparticle immunoassay (ARCHITECT Galectin-3, Abbott Germany). T1 quantification was performed at 1.5 Tesla using the modified Look-Locker inversion-recovery (MOLLI) sequence before and 15 minutes after administration of 0.075 mmol/kg gadolinium-BOPTA. Global myocardial ECV was calculated from T1 maps generated by a dedicated plug-in written for the OsiriX software. Results Median Galectin-3 level was 17.4 ng/mL (interquartile range 13.2 to 20.5 ng/mL) and median global myocardial ECV was 29 % (interquartile range 26 to 33 %) in the study population. There was a significant correlation between Galectin-3 levels and global myocardial ECV (r = 0.50; p < 0.05). In contrast, no significant correlation was found between Galectin-3 levels and LV end-diastolic volumes (r = -0.08; p = ns), LV end-systolic volumes (r = 0.06; p = ns), LV stroke volumes (r = -0.33; p = ns); LV ejection fractions (r = -0.11; p = ns), Troponin T levels (r = 0.20; p = ns) or NT-proBNP levels (r = 0.28; p = ns), respectively. Conclusions Myokardial ECV expansion, as a surrogate for myocardial injury, is associated with increased Galectin-3 levels, indicating activated fibrogenesis in patients with myocarditis. Combining Galectin-3 measurements with ECV-imaging could improve risk stratification beyond conventional imaging parameters or biomarkers in these patients.

Differentiation between active myocarditis and dilative cardiomyopathy in new-onset systolic heart failure: Potential role of T1 and T2 mapping cardiovascular magnetic resonance

Background There is an overlapping phenotype in patients with newonset systolic heart failure due to myocarditis and dilative cardiomyopathy (DCM). Differentiation between both etiologies has important therapeutic and prognostic implications and is currently based on endomyocardial biopsy (EMB). In contrast, current cardiovascular magnetic resonance (CMR) techniques are of limited value in these patients with predominantly diffuse myocardial injury. This study evaluated the performance of quantitative T1- and T2-mapping CMR to differentiate between active myocarditis and DCM in patients with new-onset systolic heart failure. Methods This study included 26 patients with new-onset systolic heart failure and reduced left ventricular (LV) ejection fraction (32 ± 12 %), who underwent EMB and CMR at 1.5 Tesla. The protocol included conventional sequences (T2w-STIR), Early- (T1w-TSE) and Late-GadoliniumEnhancement (PSIR). Furthermore, T1 quantification was performed using the modified Look-Locker inversionrecovery (MOLLI) sequence before (native) and 15 minutes after administration of 0.075 mmol/kg GadoliniumBOPTA. T2 quantification was performed using a freebreathing, navigator-gated multi-echo sequence. Native T1, post-contrast T1, extracellular volume (ECV) and T2 maps were calculated with a dedicated plug-in written for the OsiriX software. Results EMB revealed variants of active myocarditis in 13 (50 %) and DCM in the remaining 13 (50 %) patients. The ROC areas-under-the-curve (AUC) to discriminate between both etiologies was 0.54 (p = 0.77) for Early-GadoliniumEnhancement, 0.63 (p = 0.23) for Late-GadoliniumEnhancement, 0.68 (p = 0.11) for T2w-STIR, 0.66 (p = 0.17) for native global myocardial T1, 0.72 (p = 0.05) for post-contrast global myocardial T1, 0.61 (p = 0.36) for global myocardial ECV and 0.74 (p < 0.05) for global myocardial T2. Sensitivity and specificity were 50 % and 83 % to discriminate between myocarditis and DCM using global myocardial T2 (optimal cut-off ≥ 60 ms). Conclusions Assessing myocardial inflammation by T2-mapping CMR could be helpful to discriminate between active myocarditis and DCM in patients with new-onset systolic heart failure. T2-mapping CMR appears to be superior compared to conventional techniques but also to T1-mapping CMR in this context. Funding