PURPOSE: To evaluate diagnostic image quality of 3D late gadolinium enhancement (LGE) with high isotropic spatial resolution (∼1.4 mm(3) ) images reconstructed from randomly undersampled k-space using LOw-dimensional-structure Self-learning and Thresholding (LOST). MATERIALS AND METHODS: We prospectively enrolled 270 patients (181 men; 55 ± 14 years) referred for myocardial viability assessment. 3D LGE with isotropic spatial resolution of 1.4 ± 0.1 mm(3) was acquired at 1.5T using a LOST acceleration rate of 3 to 5. In a subset of 121 patients, 3D LGE or phase-sensitive LGE were acquired with parallel imaging with an acceleration rate of 2 for comparison. Two readers evaluated image quality using a scale of 1 (poor) to 4 (excellent) and assessed for scar presence. The McNemar test statistic was used to compare the proportion of detected scar between the two sequences. We assessed the association between image quality and characteristics (age, gender, torso dimension, weight, heart rate), using generalized linear models. RESULTS: Overall, LGE detection proportions for 3D LGE with LOST were similar between readers 1 and 2 (16.30% vs. 18.15%). For image quality, readers gave 85.9% and 80.0%, respectively, for images categorized as good or excellent. Overall proportion of scar presence was not statistically different from conventional 3D LGE (28% vs. 33% [P = 0.17] for reader 1 and 26% vs. 31% [P = 0.37] for reader 2). Increasing subject heart rate was associated with lower image quality (estimated slope = -0.009 (P = 0.001)). CONCLUSION: High-resolution 3D LGE with LOST yields good to excellent image quality in >80% of patients and identifies patients with LV scar at the same rate as conventional 3D LGE. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017.
PURPOSE: To compare remote myocardium native T1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. MATERIALS AND METHODS: A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T1 map was performed using a slice interleaved T1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. RESULTS: The remote myocardium native T1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P < 0.05). Remote myocardium native T1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P < 0.05). LGE infarct size had a moderate correlation with reduced LV ejection fraction (r = -0.33, P < 0.05), but there was no significant association between native T1 and infarct size. Native T1 time in the remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03). CONCLUSION: In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017.
OBJECTIVE: We aimed to investigate the association of diffuse myocardial fibrosis by cardiac magnetic resonance (CMR) T1 with complex ventricular arrhythmia (ComVA) in mitral valve prolapse (MVP). METHODS: A retrospective analysis was performed on 41 consecutive patients with MVP referred for CMR between 2006 and 2011, and 31 healthy controls. Arrhythmia analysis was available in 23 patients with MVP with Holter/event monitors. Left ventricular (LV) septal T1 times were derived from Look-Locker sequences after administration of 0.2 mmol/kg gadopentetate dimeglumine. Late gadolinium enhancement (LGE) CMR images were available for all subjects. RESULTS: Patients with MVP had significantly shorter postcontrast T1 times when compared with controls (334±52 vs 363±58 ms; p=0.03) despite similar LV ejection fraction (LVEF) (63±7 vs 60±6%, p=0.10). In a multivariable analysis, LV end-diastolic volume, LVEF and mitral regurgitation fraction were all correlates of T1 times, with LVEF and LV end-diastolic volume being the strongest (p=0.005, p=0.008 and p=0.045, respectively; model adjusted R(2)=0.30). Patients with MVP with ComVA had significantly shorter postcontrast T1 times when compared with patients with MVP without ComVA (324 (296, 348) vs 354 (327, 376) ms; p=0.03) and only 5/14 (36%) had evidence of papillary muscle LGE. CONCLUSIONS: MVP may be associated with diffuse LV myocardial fibrosis as suggested by reduced postcontrast T1 times. Diffuse interstitial derangement is linked to subclinical systolic dysfunction, and may contribute to ComVA in MVP-related mitral regurgitation, even in the absence of focal fibrosis.
BACKGROUND: T1 mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T1 mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. METHODS: A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T1 and T2 in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformité Européene (CE) marking. RESULTS: The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently-doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T1 maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the B 1 field. T1 and T2 values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15-30 °C the short-T1 tubes were more stable with temperature than the long-T1 tubes. A batch of 69 phantoms was mass-produced with random sampling of ten of these showing coefficients of variations for T1 of 0.64 ± 0.45 % and 0.49 ± 0.34 % at 1.5 T and 3 T respectively. CONCLUSION: The T1MES program has developed a T1 mapping phantom to CE/FDA manufacturing standards. An initial 69 phantoms with a multi-vendor user manual are now being scanned fortnightly in centers worldwide. Future results will explore T1 mapping sequences, platform performance, stability and the potential for standardization.
In hypertrophic cardiomyopathy (HC), there are significant variations in left ventricular (LV) wall thickness and fibrosis, which necessitates a volumetric coverage. Slice-interleaved T1 (STONE) mapping sequence allows for the assessment of native T1 time with complete coverage of LV myocardium. The aims of this study were to evaluate spatial heterogeneity of native T1 time in patients with HC. Twenty-nine patients with HC (55 ± 16 years) and 15 healthy adult control subjects (46 ± 19 years) were studied. Native T1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 seconds free-breathing scan. We measured LV native T1 time and maximum LV wall thickness in each 16 segments from 3 slices (basal, midventricular and apical slice). Late gadolinium enhanced (LGE) magnetic resonance imaging was acquired to assess the presence of myocardial enhancement. In patients with HC, LV native T1 time was significantly elevated compared with healthy controls, regardless of the presence or absence of LGE (mean native T1 time; LGE positive segments from HC, 1,141 ± 46 ms; LGE negative segments from HC, 1,114 ± 56 ms; segments from healthy controls, 1,065 ± 35 ms, p <0.001). Elevation of native T1 time was defined as >1,135 ms, which was +2SD of native T1 time by STONE sequence in healthy controls. A total of 120 of 405 (30%) LGE negative segments from patients with HC showed elevated native T1 time. Prevalence of segments with elevated native T1 time for basal, midventricular, and apical slice was 29%, 25%, 38%, respectively. Significant correlation was found between LV wall thickness and LV native T1 time (y = 0.029 × -22.6, p <0.001 by Spearman's correlation coefficient). In conclusion, substantial number of segments without LGE showed elevation of native T1 time, and whole-heart T1 mapping revealed heterogeneity of myocardial native T1 time in patients with HC.
Cardiac T1 mapping allows non-invasive imaging of interstitial diffuse fibrosis. Myocardial T1 is commonly calculated by voxel-wise fitting of the images acquired using balanced steady-state free precession (SSFP) after an inversion pulse. However, SSFP imaging is sensitive to B1 and B0 imperfection, which may result in additional artifacts. A gradient echo (GRE) imaging sequence has been used for myocardial T1 mapping; however, its use has been limited to higher magnetic field to compensate for the lower signal-to-noise ratio (SNR) of GRE versus SSFP imaging. A slice-interleaved T1 mapping (STONE) sequence with SSFP readout (STONE-SSFP) has been recently proposed for native myocardial T1 mapping, which allows longer recovery of magnetization (>8 R-R) after each inversion pulse. In this study, we hypothesize that a longer recovery allows higher SNR and enables native myocardial T1 mapping using STONE with GRE imaging readout (STONE-GRE) at 1.5T. Numerical simulations and phantom and in vivo imaging were performed to compare the performance of STONE-GRE and STONE-SSFP for native myocardial T1 mapping at 1.5T. In numerical simulations, STONE-SSFP shows sensitivity to both T2 and off resonance. Despite the insensitivity of GRE imaging to T2 , STONE-GRE remains sensitive to T2 due to the dependence of the inversion pulse performance on T2 . In the phantom study, STONE-GRE had inferior accuracy and precision and similar repeatability as compared with STONE-SSFP. In in vivo studies, STONE-GRE and STONE-SSFP had similar myocardial native T1 times, precisions, repeatabilities and subjective T1 map qualities. Despite the lower SNR of the GRE imaging readout compared with SSFP, STONE-GRE provides similar native myocardial T1 measurements, precision, repeatability, and subjective image quality when compared with STONE-SSFP at 1.5T.
BACKGROUND: Functional mitral regurgitation is one of the severe complications of non-ischemic dilated cardiomyopathy (DCM). Non-contrast native T1 mapping has emerged as a non-invasive method to evaluate myocardial fibrosis. We sought to evaluate the potential relationship between papillary muscle T1 time and mitral regurgitation in DCM patients. METHODS: Forty DCM patients (55 ± 13 years) and 20 healthy adult control subjects (54 ± 13 years) were studied. Native T1 mapping was performed using a slice interleaved T1 mapping sequence (STONE) which enables acquisition of 5 slices in the short-axis plane within a 90 s free-breathing scan. We measured papillary muscle diameter, length and shortening. DCM patients were allocated into 2 groups based on the presence or absence of functional mitral regurgitation. RESULTS: Papillary muscle T1 time was significantly elevated in DCM patients with mitral regurgitation (n = 22) in comparison to those without mitral regurgitation (n = 18) (anterior papillary muscle: 1127 ± 36 msec vs 1063 ± 16 msec, p < 0.05; posterior papillary muscle: 1124 ± 30 msec vs 1062 ± 19 msec, p < 0.05), but LV T1 time was similar (1129 ± 38 msec vs 1134 ± 58 msec, p = 0.93). Multivariate linear regression analysis showed that papillary muscle native T1 time (β = 0.10, 95 % CI: 0.05-0.17, p < 0.05) is significantly correlated with mitral regurgitant fraction. Elevated papillary muscle T1 time was associated with larger diameter, longer length and decreased papillary muscle shortening (all p values <0.05). CONCLUSIONS: In DCM, papillary muscle native T1 time is significantly elevated and related to mitral regurgitant fraction.
PURPOSE: To assess measurement reproducibility and image quality of myocardial T1 and T2 maps using free-breathing slice-interleaved T1 and T2 mapping sequences at 1.5 Tesla (T). MATERIALS AND METHODS: Eleven healthy subjects (33 ± 16 years; 6 males) underwent a slice-interleaved T1 and T2 mapping test/retest cardiac MR study at 1.5T on 2 days. For each day, subjects were imaged in two sessions with removal out of the magnet and repositioning before the subsequent session. We studied measurement reproducibility as well as the required sample size for sufficient statistical power to detect a predefined change in T1 and T2 . In a separate prospective study, we assessed T1 and T2 map image quality in 241 patients (54 ± 15 years; 73 women) with known/suspected cardiovascular disease referred for clinical cardiac MR. A subjective quality score was used to assess a segment-based image quality. RESULTS: In the healthy cohort, the slice-interleaved T1 measurements were highly reproducible, with global coefficients of variation (CVs) of 2.4% between subjects, 2.1% between days, and 1.7% between sessions. Slice-interleaved T2 mapping sequences provided similar reproducibility with global CVs of 7.2% between subjects, 6.3% between days, and 5.0 between sessions. A lower variability resulted in a reduction of the required number of subjects to achieve a certain statistical power when compared with other T1 mapping sequences. In the subjective image quality assessment, >80% of myocardial segments had interpretable data. CONCLUSION: Slice-interleaved T1 and T2 mapping sequences yield highly reproducible T1 and T2 measurements with >80% of interpretable myocardial segments. J. Magn. Reson. Imaging 2016;44:1159-1167.
BACKGROUND: Mapping resolution is influenced by electrode size and interelectrode spacing. The aims of this study were to establish normal electrogram criteria for 1-mm multielectrode-mapping catheters (Pentaray) in the ventricle and to compare its mapping resolution within scar to standard 3.5-mm catheters (Smart-Touch Thermocool). METHODS AND RESULTS: Three healthy swine and 11 swine with healed myocardial infarction underwent sequential mapping of the left ventricle with both catheters. Bipolar voltage amplitude in healthy tissue was similar between 3.5- and 1-mm multielectrode catheters with a 5th percentile of 1.61 and 1.48 mV, respectively. In swine with healed infarction, the total area of low bipolar voltage amplitude (defined as <1.5 mV) was 22.5% smaller using 1-mm multielectrode catheters (21.7 versus 28.0 cm2; P=0.003). This was more evident in the area of dense scar (bipolar amplitude <0.5 mV) with a 47% smaller very low-voltage area identified using 1-mm electrode catheters (7.1 versus 15.2 cm(2); P=0.003). In this region, 1-mm multielectrode catheters recorded higher voltage amplitude (0.72±0.81 mV versus 0.30±0.12 mV; P<0.001). Importantly, 27% of these dense scar electrograms showed distinct triphasic electrograms when mapped using a 1-mm multielectrode catheter compared with fractionated multicomponent electrogram recorded with the 3.5-mm electrode catheter. In 8 mapped reentrant ventricular tachycardias, the circuits included regions of preserved myocardial tissue channels identified with 1-mm multielectrode catheters but not 3.5-mm electrode catheters. Pacing threshold within the area of low voltage was lower with 1-mm electrode catheters (0.9±1.3 mV versus 3.8±3.7 mV; P=0.001). CONCLUSIONS: Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.
Diffuse myocardial fibrosis is involved in the pathology of nonischemic cardiomyopathy (NIC). Recently, the application of native (noncontrast) myocardial T1 measurement has been proposed as a method for characterizing diffuse interstitial fibrosis. To determine the association of native T1 with myocardial structure and function, we prospectively studied 39 patients with NIC (defined as left ventricular ejection fraction (LVEF) ≤ 50% without cardiac magnetic resonance (CMR) evidence of previous infarction) and 27 subjects with normal LVEF without known overt cardiovascular disease. T1, T2, and extracellular volume fraction (ECV) were determined over 16 segments across the base, mid, and apical left ventricular (LV). NIC participants (57 ± 15 years) were predominantly men (74%), with a mean LVEF 34 ± 10%. Subjects with NIC had a greater native T1 (1,131 ± 51 vs 1,069 ± 29 ms; p <0.0001), a greater ECV (0.28 ± 0.04 vs 0.25 ± 0.02, p = 0.002), and a longer myocardial T2 (52 ± 8 vs 47 ± 5 ms; p = 0.02). After multivariate adjustment, a lower global native T1 time in NIC was associated with a greater LVEF (β = -0.59, p = 0.0003), greater right ventricular ejection fraction (β = -0.47, p = 0.006), and smaller left atrial volume index (β = 0.51, p = 0.001). The regional distribution of native myocardial T1 was similar in patients with and without NIC. In NIC, native myocardial T1 is elevated in all myocardial segments, suggesting a global (not regional) abnormality of myocardial tissue composition. In conclusion, native T1 may represent a rapid, noncontrast alternative to ECV for delineating myocardial tissue remodeling in NIC.
BACKGROUND: Native T1 mapping has emerged as a noninvasive non-contrast magnetic resonance imaging (MRI) method to assess for diffuse myocardial fibrosis. However, LV native T1 time in AF patients and its clinical relevance are unclear. METHODS: Fifty paroxysmal AF patients referred for PVI (60 ± 8 years, 37 male) and 11 healthy control subjects (57 ± 8 years, 10 male) were studied. All patients were in sinus rhythm during the MRI scan. Native T1 mapping images were acquired using a Modified Look-Locker imaging (MOLLI) sequence in 3 short-axis planes (basal, mid and apical slices) using an electrocardiogram triggered single-shot acquisition with a balanced steady-state free precession readout. Late gadolinium enhanced (LGE) MRI was acquired to evaluate for LV myocardial scar. RESULTS: LV ejection fraction was similar between groups (AF: 61 ± 6%; controls: 60 ± 6%, p=0.75). No LV myocardial scar was observed in any patient on LGE. Myocardial native T1 time was greater in AF patients (1099 ± 52 vs 1042 ± 20 msec, p<0.001). During a median follow-up period of 326 days, 18 of 50 (36%) patients experienced recurrence of AF. Multivariate Cox proportional hazard analysis identified elevated native T1 time as an independent predictor of recurrence of AF (HR: 6.53, 95% CI: 1.25-34.3, p=0.026). CONCLUSIONS: There are differences in the native LV myocardial T1 time between AF patients with preserved LV function referred for PVI and normal controls. Native T1 time is an independent predictor of recurrence of AF after PVI in patients with paroxysmal AF.
BACKGROUND: Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. OBJECTIVE: We aimed to develop and characterize a swine model of scar-related reentrant VT. METHODS: Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 6-8-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. RESULTS: Left ventricular (LV) ejection fraction measured using CMR imaging was 36% ± 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% ± 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% ± 3.5% of the LV surface area (bipolar voltage ≤1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with "pseudo-block" due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 ± 1.1; range 1-4) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. CONCLUSION: This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction reentrant VT.
PURPOSE: To develop a novel MR sequence for combined three-dimensional (3D) phase-sensitive (PS) late gadolinium enhancement (LGE) and T1 mapping to allow for simultaneous assessment of focal and diffuse myocardial fibrosis. METHODS: In the proposed sequence, four 3D imaging volumes are acquired with different T1 weightings using a combined saturation and inversion preparation, after administration of a gadolinium contrast agent. One image is acquired fully sampled with the inversion time selected to null the healthy myocardial signal (the LGE image). The other three images are three-fold under-sampled and reconstructed using compressed sensing. An acquisition scheme with two interleaved imaging cycles and joint navigator-gating of those cycles ensures spatial registration of the imaging volumes. T1 maps are generated using all four imaging volumes. The signal-polarity in the LGE image is restored using supplementary information from the T1 fit to generate PS-LGE images. The accuracy of the proposed method was assessed with respect to a inversion-recovery spin-echo sequence. In vivo T1 maps and LGE images were acquired with the proposed sequence and quantitatively compared with 2D multislice Modified Look-Locker inversion recovery (MOLLI) T1 maps. Exemplary images in a patient with focal scar were compared with conventional LGE imaging. RESULTS: The deviation of the proposed method and the spin-echo reference was < 11 ms in phantom for T1 times between 250 and 600 ms, regardless of the inversion time selected in the LGE image. There was no significant difference in the in vivo T1 times of the proposed sequence and the 2D MOLLI technique (myocardium: 292 ± 75 ms versus 310 ± 49 ms, blood-pools: 191 ± 75 ms versus 182.0 ± 33). The LGE images showed proper nulling of the healthy myocardium in all subjects and clear depiction of scar in the patient. CONCLUSION: The proposed sequence enables simultaneous acquisition of 3D PS-LGE images and spatially registered 3D T1 maps in a single scan.
PURPOSE: To provide a method for the optimal selection of sampling points for myocardial T1 mapping, and to evaluate how this selection affects the precision. THEORY: The Cramér-Rao lower bound on the variance of the unbiased estimator was derived for the sampling of the longitudinal magnetization curve, as a function of T1 , signal-to-noise ratio, and noise mean. The bound was then minimized numerically over a search space of possible sampling points to find the optimal selection of sampling points. METHODS: Numerical simulations were carried out for a saturation recovery-based T1 mapping sequence, comparing the proposed point selection method to a uniform distribution of sampling points along the recovery curve for various T1 ranges of interest, as well as number of sampling points. Phantom imaging was performed to replicate the scenarios in numerical simulations. In vivo imaging for myocardial T1 mapping was also performed in healthy subjects. RESULTS: Numerical simulations show that the precision can be improved by 13-25% by selecting the sampling points according to the target T1 values of interest. Results of the phantom imaging were not significantly different than the theoretical predictions for different sampling strategies, signal-to-noise ratio and number of sampling points. In vivo imaging showed precision can be improved in myocardial T1 mapping using the proposed point selection method as predicted by theory. CONCLUSION: The framework presented can be used to select the sampling points to improve the precision without penalties on accuracy or scan time.