Equilibrium Contrast CMR Research Articles

Diffuse myocardial fibrosis in adolescents operated with arterial switch for transposition of the great arteries - A CMR study

Diffuse myocardial fibrosis in adolescents operated with arterial switch for transposition of the great arteries - A CMR study

Circulation : Cardiovascular Imaging

<i>Circulation</i> : <i>Cardiovascular Imaging</i>

T1 Mapping in Heart Failure

Cardiovascular magnetic resonance (CMR) is increasingly used in the assessment of heart failure and cardiomyopathy because it offers uniquely precise noninvasive phenotypic characterization. Beyond enabling highly accurate and reproducible quantification of ventricular volumes and ejection fraction, the power of this technique was further established by the application of late gadolinium enhancement to identify scar, which has both diagnostic and prognostic use. Although this regional replacement fibrosis can be identified by late gadolinium enhancement and is clearly associated with adverse outcome in several cardiomyopathies,1,2 it is mostly irreversible. In contrast, reactive interstitial fibrosis, generally a precursor of replacement fibrosis, is potentially reversible. In reality, reactive fibrosis and replacement fibrosis are on a continuum. It is appreciated that a significant myocardial process is not identified by conventional late gadolinium enhancement CMR (in the absence of adequate expansion of the extracellular space) in a variety of cardiac conditions and that this undetected common pathology is diffuse interstitial fibrosis. Article see p 1056 T1 mapping to assess extracellular volume (ECV) as a biomarker for diffuse myocardial fibrosis is currently a hot topic in the literature because this technique has emerged from its infancy and developed during the past decade, proliferating during the past 3 years.2 T1 maps can be produced of the native T1 value of tissue (informing with regard to both the myocyte and the interstitium) or after gadolinium contrast administration (enabling quantification of the extracellular space). The current gold standard technique for ECV quantification is equilibrium contrast CMR as described by Flett et al,3 with continuing development.4,5 T1 mapping may be sensitive to myocardial involvement under several conditions long before other changes are evident by biochemical, imaging or clinical …

T1 Mapping for Myocardial Extracellular Volume Measurement by CMR: Bolus Only Versus Primed Infusion Technique

The aim of this study was to determine the accuracy of the contrast "bolus only" T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume fraction (ECV).Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions.One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF.The ECV by both techniques correlated with histological CVF (n = 18, r² = 0.69, p < 0.01 vs. r² = 0.71, p < 0.01, p = 0.42 for comparison). Across health and disease, there was strong correlation between the techniques (r² = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV <0.4 = -0.004 ± 0.037 vs. ECV >0.4 = 0.040 ± 0.075, p < 0.001).Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.

Diffuse myocardial fibrosis in the systemic right ventricle of patients late after Mustard or Senning surgery: an equilibrium contrast cardiovascular magnetic resonance study

After atrial redirection surgery (Mustard-Senning operations) for transposition of the great arteries (TGA), the systemic right ventricle (RV) suffers from late systolic failure with high morbidity and mortality. Mechanisms of late RV failure are poorly characterized. We hypothesized that diffuse interstitial expansion representing diffuse fibrosis is greater in systemic RVs of patients following Mustard-Senning surgery and that it would be associated with other markers of heart failure and disease severity. We used equilibrium contrast cardiovascular magnetic resonance (CMR) imaging to quantify extracellular volume (ECV) in the septum and RV free wall of 14 adults presenting to a specialist clinic late after surgery for TGA (8 Mustard, 6 female, median age 33). These were compared with 14 age-and sex-matched healthy volunteers. Patients were assessed with a standardized CMR protocol, NT-brain natriuretic peptide (NT-proBNP), and cardiopulmonary exercise (CPEX) testing. The mean septal ECV was significantly higher in patients than controls (0.254 ± 0.036 vs. 0.230 ± 0.032; P = 0.03). NT-proBNP positively related to septal ECV (P = 0.04; r = 0.55). The chronotropic index (CI) during CPEX testing negatively related to the ECV (P = 0.04; r = -0.58). No relationship was seen with other CMR or CPEX parameters. R.V free wall ECV was difficult to measure (heavy trabeculation, sternal wires, blood pool in regions of interest) with high and poor inter-observer reproducibility: this analysis was abandoned. Septal interstitial expansion is seen in adults late after atrial redirection surgery for TGA. It correlates well with NT-proBNP and CI and may have a role in the development of RV systolic impairment. Measuring interstitial expansion in the RV free wall is difficult using this methodology.

Quantification of Myocardial Extracellular Volume Fraction in Systemic AL Amyloidosis

Background— Cardiac involvement predicts outcome in systemic AL amyloidosis and influences therapeutic options. Current methods of cardiac assessment do not quantify myocardial amyloid burden. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) to quantify the cardiac interstitial compartment, measured as myocardial extracellular volume (ECV) fraction, hypothesizing it would reflect amyloid burden. Methods and Results— Sixty patients with systemic AL amyloidosis (65% men, median age 65 years) underwent conventional clinical cardiovascular magnetic resonance, including late enhancement, equilibrium contrast cardiovascular magnetic resonance, and clinical cardiac evaluation, including ECG, echocardiography, assays of N-terminal pro-brain natriuretic peptide and Troponin T, and functional assessment comprising the 6-minute walk test in ambulant individuals. Cardiac involvement in the amyloidosis patients was categorized as definite, probable, or none, suspected by conventional criteria. Findings were compared with 82 healthy controls. Mean ECV was significantly greater in patients than healthy controls (0.25 versus 0.40, P &lt;0.001) and correlated with conventional criteria for characterizing the presence of cardiac involvement, the categories of none, probable, definite corresponding to ECV of 0.276 versus 0.342 versus 0.488, respectively ( P &lt;0.001). ECV was correlated with cardiac parameters by echocardiography (eg, Tissue Doppler Imaging [TDI] S-wave R=0.52, P&lt;0.001) and conventional cardiovascular magnetic resonance (eg, indexed left ventricular mass R =0.56, P &lt;0.001). There were also significant correlations with N-terminal pro-brain natriuretic peptide ( R =0.69, P &lt;0.001) and Troponin T ( R =0.53, P =0.006). ECV was associated with smaller QRS voltages ( R =0.57, P &lt;0.001) and correlated with poorer performance in the 6-minute walk test ( R =0.36, P =0.03). Conclusions— Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.

Interstitial expansion in pressure overload left ventricular hypertrophy

Background Diffuse myocardial fibrosis (DMF) is an important factor in cardiac disease, but until recently could only be accurately assessed with biopsy. We hypothesised that DMF measured by Equilibrium contrast CMR (EQ-CMR) is elevated in cardiac pressure overload (hypertension and aortic stenosis), that the degree of DMF will track the clinical severity of pressure overload and cardiac effects, and as such DMF may be a key biomarker in assessing the cardiac effects of pressure overload.

Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease

ObjectiveTo measure and assess the significance of myocardial extracellular volume (ECV), determined non-invasively by equilibrium contrast cardiovascular magnetic resonance, as a clinical biomarker in health and a number of cardiac...

Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study

Haemodynamics alone do not fully explain symptoms and prognosis in clinically severe aortic stenosis (AS). Myocardial disease, specifically diffuse myocardial fibrosis (DMF), may contribute. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) and sought to non-invasively measure DMF in severe AS and determine its clinical significance before and after valve replacement. Patients with severe AS underwent echocardiography, brain natriuretic peptide (BNP), 6 min walk test (6MWT), and EQ-CMR pre- (n = 63) at baseline and at 6 months post- (n = 42) aortic valve replacement (AVR). EQ-CMR was also performed in 30 normal controls. Baseline: patients with AS had more DMF than controls (18 vs. 13%, P = 0.007) with a wide range (5-38%) that overlapped controls. The extent of diffuse fibrosis correlated inversely with the 6MWT performance (r(2) = 0.22, P = 0.001). Those with severe diastolic dysfunction had more DMF (P = 0.01). On multivariable analysis, the predictors of performance at 6MWT were diffuse fibrosis and BNP (P = 0.003 and 0.02, respectively). Post-op: following valve replacement, morphological and functional parameters improved [6 MWT, LA area, BNP, left ventricular (LV) hypertrophy, and volumes]. LV hypertrophy regression was shown to be cell volume reduction (P < 0.001) and not fibrosis regression (P = 0.54). Of the five deaths over six-month follow-up, four occurred in patients in the highest tertile of DMF. DMF as measured by EQ-CMR is elevated in severe AS vs. normal controls but with a considerable overlap. It correlates with functional capacity at baseline. LV hypertrophy regression 6 months after AVR is cellular rather than fibrosis resolution.

093 Cardiac involvement in cardiac al amyloidosis as measured by equilibrium contrast cardiovascular magnetic resonance

IntroductionCardiac involvement drives prognosis in Systemic AL Amyloidosis, predicting outcome and influencing therapeutic options. Current methods of cardiac assessment do not quantify the myocardial amyloid burden. We used Equilibrium Contrast...

092 Interstitial expansion in health and disease—an equilibrium contrast CMR study

IntroductionInterstitial myocardial volume expansion is an important factor in cardiac disease but until recently could only be accurately assessed with myocardial biopsy. It is usually a result of diffuse fibrosis,...

Cardiac involvement in cardiac AL amyloidosis as measured by equilibrium contrast cardiovascular magnetic resonance

Background Involvement of the heart drives prognosis in Systemic AL Amyloidosis, predicting outcome and influencing therapeutic options. Current methods of cardiac assessment do not allow formal quantification of the amyloid load. We used Equilibrium Contrast Cardiovascular Magnetic Resonance (EQ-CMR) to measure the interstitial compartment of the heart by measuring the myocardial contrast volume of distribution, VDm.

Assessment of the interstitial volume in healthy volunteers. An equilibrium contrast CMR study

Summary In this study we have used Equilibrium contrast CMR (EQ-CMR) to evaluate the cardiac insterstium in healthy volunteers creating a table of normal values and finding no correlation with age, but differences with gender, height and hematocrit. Background EQ-CMR is a new method for assessment of the myocardial contrast volume of distribution, Vd(m), a marker of interstitial space. We used EQ-CMR to assess the Vd (m) in healthy volunteers to ascertain normal age/gender values. Methods 86 healthy subjects (median age 45, range 24-81, 42 males) were recruited from hospital, university or via a local General Practitioner surgery. All were assessed with a cardiac history and examination, routine blood tests, 12 lead ECG, blood pressure and clinical CMR. Volunteers were excluded if any evidence of cardiovascular disease was found. Baseline differences between male and female volunteers were found, with the latter having a faster heart rate, smaller left ventricular volumes, shorter height, lower weight and lower hematocrit. Results Mean Vd(m) was 0.255±0.035. There was no significant correlation between age and Vd(m) (R=0.15, P=0.16, Fig 1). Vd(m) in females was significantly higher than males (0.275±0.028 vs 0.237±0.031, P<0.001) Fig 2). Negative correlations were found between Vd(m) and height (R=0.41, P<0.001), left ventricular mass (-0.38, P<0.001) and hematocrit (R=-0.41 P<0.001) - this last variable in females but not males. Conclusions Vd(m) did not change with age, but did with gender, height and hematocrit. Several plausible biological explanations exist for this gender finding, and support for the lack of age related changes exists in two large human necropsy studies. Further work will be required to evaluate these findings further.

Equilibrium contrast cardiovascular magnetic resonance shows increased interstitial expansion in the systemic right ventricle of adults late after Mustard or Senning surgery for transposition of the great arteries

Summary In this study, we have used equilibium contrast CMR (EQ-CMR) to assess the interstium volume of patients after atrial redirection surgery, finding higher amounts than in healthy volunteers and correlations with known clinical markers of disease. Background After atrial redirection surgery (the Mustard and Senning operations) for transposition of the great arteries (TGA) the systemic right ventricle (RV) suffers from late systolic failure with resultant high morbidity and mortality. The mechanisms of late systemic RV failure are poorly characterised. We hypothesised that diffuse interstitial expansion representing diffuse fibrosis would be greater in the right ventricles of patients following Mustard or Senning surgery and that it would be associated with other markers of heart failure and disease severity in these patients. Methods

Not all LGE is the same. Scar contrast volume of distribution is lower in HCM than in infarction

Background Focal fibrosis is visible as late gadolinium enhancement when using inversion recovery (IR) imaging late after a contrast bolus and carries major clinical import. The IR technique results in high sensitivity to regional T1 variation but sacrifices absolute quantification meaning that differing degrees of focal interstitial expansion will look the same (bright). We hypothesized that LGE in different disease processes would have different degrees of interstitial expansion. We used equilibrium contrast CMR (EQ-CMR), to measure the degree of interstitial expansion by measuring the volume of distribution of contrast, Vd(m).

Single breath-hold Vd(m) calculation as good as multi breath-hold technique in Equilibrium Contrast CMR

In this study we have compared the multi flip angle (MFA) FLASH T1 mapping technique to shortened look locker inversion recovery (ShMOLLI) for assessment of pre and post contrast T1 for equilibium contrast CMR (EQ-CMR) and also potential pseudoequilibrium post bolus. Good agreement was found in the volume of distribution, Vd(m), between both techniques and at equilibirum.

Interstitial expansion in health and disease - an equilibrium contrast CMR study

In this study of 278 particiapnts, we aimed to evaluate the cardiac interstitium in health and disease using Equilibrium constrast CMR (EQ-CMR). We found gender and disease differences in the contrast myocardial volume of distribution Vd(m) and correlations with clinical CMR markers of disease.

Histological validation of ShMOLLI equilibrium contrast CMR for the measurement of diffuse myocardial fibrosis

Methods In fourteen patients with symptomatic severe aortic stenosis awaiting valve surgery, we performed equilibrium contrast CMR (EQ-CMR: [Flett AS et al. Circulation 2010;122(2):138-44]) to calculate Vd(m) using ShMOLLI (Shortened Modified Look-Locker Inversion recovery [Piechnik at al. JCMR 2010;12:69]) and standard multibreathold (FLASH) mapping, for the pre and equilibrium contrast T1 mapping. We compared the results to surgical biopsy. Vd(m) was calculated by Vd(m)=(1-hematocrit)xΔ(1/ T1)myo ÷ Δ(1/T1)blood. Surgical left ventricular septal biopsies were fixed and stained with picrosirius red and then digitally photographed. Collagen volume fraction (CVF%) was calculated by a blinded observer using in-house software (macro written in Image J) for automated analysis. Patients with LGE in the biopsy area were pre-specified as being excluded from analysis.

The quantification and role of diffuse myocardial fibrosis in familial dilated cardiomyopathy - an equilibrium contrast cmr study

Objective To evaluate the role of diffuse myocardial fibrosis (DMF) in familial Dilated Cardiomyopathy (fDCM) using Equilibrium Contrast-CMR (EQ-CMR). Background Post mortem/biopsy studies have shown that DMF occurs in DCM, but its clinical significance remains largely unknown as its assessment requires invasive biopsy. EQ-CMR is a recently described technique that permits the non-invasive and accurate assessment of DMF by measuring the myocardial contrast volume of distribution (Vd(m)) at equilibrium contrast [1]. Methods Using international diagnostic guidelines we identified 28 patients with fDCM (mean age 42, 61% male, 89% NYHA class I, 11% NYHA class II). This cohort excluded the most severe cases of fDCM due to the high prevalence of permanent pacemakers or ICDs. The Vd(m) (a measure of DMF) was compared to that obtained in healthy volunteers (mean age 35, 63% male) and also to other indexed CMR parameters, including left atrial area and echocardiographic parameters of diastolic function (tissue doppler and strain imaging). Results fDCM patients had increased LV size (95mls/m2 vs 73mls/m2 , p=0.0001), worse ejection fraction (55% vs 69%, p<0.0001), increased indexed left atrial area (LAAi) (12.3cm2/m2 vs 9.5cm2/m2, p=0.0004) when compared to healthy volunteers. Significantly impaired diastolic function was detected in 14% of fDCM patients. No patients had worse than mild mitral regurgitation. The Vd(m) in patients was significantly greater than that of healthy volunteers (Fig 1) (0.282 vs 0.234, p=0.003). Vd(m) correlated with LAAi (fig 2) (r2= 0.44, p<0.0001) and EF (r2=0.12, p=0.034), but was independent of indexed LV diastolic volume, mass and echocardiographic derived parameters of diastolic function. On univariate analysis, LAAi was predicted by both Vd(m) (r2= 0.44) and E/Ea (r2= 0.31), which on multivariate analysis were independent with Vd(m) being the strongest predictor.

Beyond late gadolinium enhancement: the key role of diffuse myocardial fibrosis in severe aortic stenosis - an Equilibrium Contrast CMR study

Background In severe aortic stenosis (AS), hemodynamics and conventional indices do not fully explain symptoms, prognosis or treatment response. We hypothesize that diffuse myocardial fibrosis (DMF) is a key missing factor in AS. This can now be accurately measured non-invasively using equilibrium contrast CMR (EQ-CMR) [1] involving a primed gadolinium infusion, T1 measurement preand post-infusion, and direct measure of blood volume of distribution (1-hematocrit). The derived myocardial volume of distribution (Vd(m)) correlates strongly with histological diffuse myocardial fibrosisin AS and this calibration can convert Vd(m) to DMF%. Cell volume can be calculated as 1-DMF%*LV mass.