Jing Han

Myocardial T1 and Extracellular Volume Fraction Mapping at 3 Tesla

BackgroundTo compare 11 heartbeat (HB) and 17 HB modified lock locker inversion recovery (MOLLI) pulse sequence at 3T and to establish preliminary reference values for myocardial T1 and the extracellular volume fraction (ECV).MethodsBoth phantoms and normal volunteers were scanned at 3T using 11 HB and 17 HB MOLLI sequence with the following parameters: spatial resolution = 1.75 × 1.75 × 10 mm on a 256 × 180 matrix, TI initial = 110 ms, TI increment = 80 ms, flip angle = 35°, TR/TE = 1.9/1.0 ms. All volunteers were administered Gadolinium-DTPA (Magnevist, 0.15 mmol/kg), and multiple post-contrast MOLLI scans were performed at the same pre-contrast position from 3.5-23.5 minutes after a bolus contrast injection. Late gadolinium enhancement (LGE) images were also acquired 12-30 minutes after the gadolinium bolus.ResultsT1 values of 11 HB and 17 HB MOLLI displayed good agreement in both phantom and volunteers. The average pre-contrast myocardial and blood T1 was 1315 ± 39 ms and 2020 ± 129 ms, respectively. ECV was stable between 8.5 to 23.5 minutes post contrast with an average of 26.7 ± 1.0%.ConclusionThe 11 HB MOLLI is a faster method for high-resolution myocardial T1 mapping at 3T. ECV fractions are stable over a wide time range after contrast administration.

Relative Importance of Errors in Left Ventricular Quantitation by Two-Dimensional Echocardiography: Insights From Three-Dimensional Echocardiography and Cardiac Magnetic Resonance Imaging

BACKGROUND The accuracy of left ventricular (LV) volumes and ejection fraction (EF) on two-dimensional echocardiography (2DE) is limited by image position (IP), geometric assumption (GA), and boundary tracing (BT) errors. METHODS Real-time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR) were used to determine the relative contribution of each error source in normal controls (n = 35) and patients with myocardial infarctions (MIs) (n = 34). LV volumes and EFs were calculated using (1) apical biplane disk summation on 2DE (IP + GA + BT errors), (2) biplane disk summation on RT3DE (GA + BT errors), (3) 4-multiplane to 8-multiplane surface approximation on RT3DE (GA + BT errors), (4) voxel-based surface approximation on RT3DE (BT error alone) and (5) CMR. By comparing each method with CMR, the absolute and relative contributions of each error source were determined. RESULTS IP error predominated in LV volume quantification on 2DE in normal controls, whereas GA error predominated in patients with MIs. Underestimation of volumes on 2DE was overcome by increasing the number of imaging planes on RT3DE. Although 4 equidistant image planes were acceptable, the best results were achieved with voxel-based RT3DE. For EF estimation, IP error predominated in normal controls, whereas BT error predominated in patients with MIs. Nevertheless, one third of the EF estimation error in patients with MIs was due to a combination of IP and GA errors, both of which may be addressed using RT3DE. CONCLUSIONS The relative contribution of each source of LV quantitation error on 2DE was defined and quantified. Each source of error differed depending on patient characteristics and LV geometry.

Association Between Elevated Fibrosis Markers and Heart Failure in the Elderly The Cardiovascular Health Study

Background—Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly. Methods and Results—Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77±6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction ≥55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001). Conclusions—Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.

Diffuse myocardial fibrosis evaluation using cardiac magnetic resonance T1 mapping: sample size considerations for clinical trials

BackgroundCardiac magnetic resonance (CMR) T1 mapping has been used to characterize myocardial diffuse fibrosis. The aim of this study is to determine the reproducibility and sample size of CMR fibrosis measurements that would be applicable in clinical trials.MethodsA modified Look-Locker with inversion recovery (MOLLI) sequence was used to determine myocardial T1 values pre-, and 12 and 25min post-administration of a gadolinium-based contrast agent at 3 Tesla. For 24 healthy subjects (8 men; 29 ± 6 years), two separate scans were obtained a) with a bolus of 0.15mmol/kg of gadopentate dimeglumine and b) 0.1mmol/kg of gadobenate dimeglumine, respectively, with averaged of 51 ± 34 days between two scans. Separately, 25 heart failure subjects (12 men; 63 ± 14 years), were evaluated after a bolus of 0.15mmol/kg of gadopentate dimeglumine. Myocardial partition coefficient (λ) was calculated according to (ΔR1myocardium/ΔR1blood), and ECV was derived from λ by adjusting (1-hematocrit).ResultsMean ECV and λ were both significantly higher in HF subjects than healthy (ECV: 0.287 ± 0.034 vs. 0.267 ± 0.028, p=0.002; λ: 0.481 ± 0.052 vs. 442 ± 0.037, p < 0.001, respectively). The inter-study ECV and λ variation were about 2.8 times greater than the intra-study ECV and λ variation in healthy subjects (ECV:0.017 vs. 0.006, λ:0.025 vs. 0.009, respectively). The estimated sample size to detect ECV change of 0.038 or λ change of 0.063 (corresponding to ~3% increase of histological myocardial fibrosis) with a power of 80% and an alpha error of 0.05 for heart failure subjects using a two group design was 27 in each group, respectively.ConclusionECV and λ quantification have a low variability across scans, and could be a viable tool for evaluating clinical trial outcome.

Modified look-locker inversion recovery T1 mapping indices: assessment of accuracy and reproducibility between magnetic resonance scanners.

BackgroundCardiovascular magnetic resonance (CMR) T1 mapping indices, such as T1 time and partition coefficient (λ), have shown potential to assess diffuse myocardial fibrosis. The purpose of this study was to investigate how scanner and field strength variation affect the accuracy and precision/reproducibility of T1 mapping indices.MethodsCMR studies were performed on two 1.5T and three 3T scanners. Eight phantoms were made to mimic the T1/T2 of pre- and post-contrast myocardium and blood at 1.5T and 3T. T1 mapping using MOLLI was performed with simulated heart rate of 40-100 bpm. Inversion recovery spin echo (IR-SE) was the reference standard for T1 determination. Accuracy was defined as the percent error between MOLLI and IR-SE, and scan/re-scan reproducibility was defined as the relative percent mean difference between repeat MOLLI scans. Partition coefficient was estimated by ΔR1myocardium phantom/ΔR1blood phantom. Generalized linear mixed model was used to compare the accuracy and precision/reproducibility of T1 and λ across field strength, scanners, and protocols.ResultsField strength significantly affected MOLLI T1 accuracy (6.3% error for 1.5T vs. 10.8% error for 3T, p<0.001) but not λ accuracy (8.8% error for 1.5T vs. 8.0% error for 3T, p=0.11). Partition coefficients of MOLLI were not different between two 1.5T scanners (47.2% vs. 47.9%, p=0.13), and showed only slight variation across three 3T scanners (49.2% vs. 49.8% vs. 49.9%, p=0.016). Partition coefficient also had significantly lower percent error for precision (better scan/re-scan reproducibility) than measurement of individual T1 values (3.6% for λ vs. 4.3%-4.8% for T1 values, approximately, for pre/post blood and myocardium values).ConclusionBased on phantom studies, T1 errors using MOLLI ranged from 6-14% across various MR scanners while errors for partition coefficient were less (6-10%). Compared with absolute T1 times, partition coefficient showed less variability across platforms and field strengths as well as higher precision.

Association Between Elevated Fibrosis Markers and Heart Failure in the ElderlyCLINICAL PERSPECTIVE

Background—Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly. Methods and Results—Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77±6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction ≥55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001). Conclusions—Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.

The Relationship between Serum Markers of Collagen Turnover and Cardiovascular Outcome in the Elderly: The Cardiovascular Health Study

Background— The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals. Methods and Results— In 880 participants in the Cardiovascular Health Study (mean age, 77±6 years; 48% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF; n=175, EF ≥55%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12±4 years (range, 3–17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups. Conclusions— In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

Myocardial and blood T1 quantification in normal volunteers at 3T

T1 mapping is a novel quantitative method for myocardial tissue characterization. Reference values of myocardium and blood have been established at 1.5T (Messroghli, MRM, 2007). CMR at 3T is a rapidly maturing field, and T1 values generally increase with magnetic field strength, making it necessary to establish new reference values at this higher field strength. The aim of this study is to establish pre- and post-contrast myocardium and blood reference T1 values at 3T.

Sample size calculation for clinical trials using cardiac magnetic resonance partition coefficient and extracellular volume fraction for the assessment of diffuse myocardial fibrosis

Methods A modified Look-Locker with inversion recovery (MOLLI) sequence was used to determine myocardial T1 values pre-, and 12 and 25 min post-administration of a gadolinium-based contrast agent at 3 Tesla. For 24 healthy subjects (8 men; 29±6 years), two separate scans were obtained a) with a bolus of 0.15 mmol/kg of gadopentate dimeglumine and b) 0.1 mmol/kg of gadobenate dimeglumine, respectively, with averaged of 51±34 days between two scans. Separately, 25 heart failure subjects (12 men; 63±14 years), were evaluated after a bolus of 0.15mmol/kg of gadopentate dimeglumine. Myocardial partition coefficient (l) was calculated according to (ΔR1myocardium/ΔR1blood), and ECV was derived from l by adjusting (1-hematocrit).

Phantom validation of 17 and 11 heartbeat MOLLI T1 mapping sequence at 3T.

Background and objective The Modified Look-Locker Inversion-Recovery (MOLLI) sequence (Messroghli, et al, JMRI, 2007) was optimized for myocardial T1 mapping on 1.5T. However, little data exists on T1 mapping at 3T. The standard MOLLI sequence uses three inversion-recovery blocks to acquire 11 images over 17 heartbeats (HB). The long breath hold could limit its clinical application in patients with cardiorespiratory compromise. A new 11 HB MOLLI protocol with two inversion-recovery blocks was introduced recently, which reduces scan time by 35%. This aim of this study is to verify both 17 HB and 11 HB MOLLI sequences at 3T.