Hossam El-Rewaidy, Maryam Nezafat, Jihye Jang, Shiro Nakamori, Ahmed Fahmy, and Reza Nezafat. 2018. “Nonrigid Active Shape Model-Based Registration Framework for Motion Correction of Cardiac T1 Mapping.” Magn Reson Med.Abstract

PURPOSE: Accurate reconstruction of myocardial T1 maps from a series of T1-weighted images consists of cardiac motions induced from breathing and diaphragmatic drifts. We propose and evaluate a new framework based on active shape models to correct for motion in myocardial T1 maps.
METHODS: Multiple appearance models were built at different inversion time intervals to model the blood-myocardium contrast and brightness changes during the longitudinal relaxation. Myocardial inner and outer borders were automatically segmented using the built models, and the extracted contours were used to register the T1-weighted images. Data acquired from 210 patients using a free-breathing acquisition protocol were used to train and evaluate the proposed framework. Two independent readers evaluated the quality of the T1 maps before and after correction using a four-point score. The mean absolute distance and Dice index were used to validate the registration process.
RESULTS: The testing data set from 180 patients at 5 short axial slices showed a significant decrease of mean absolute distance (from 3.3 ± 1.6 to 2.3 ± 0.8 mm, P < 0.001) and increase of Dice (from 0.89 ± 0.08 to 0.94 ± 0.4%, P < 0.001) before and after correction, respectively. The T1 map quality improved in 70 ± 0.3% of the motion-affected maps after correction. Motion-corrupted segments of the myocardium reduced from 21.8 to 8.5% (P < 0.001) after correction.
CONCLUSION: The proposed method for nonrigid registration of T1-weighted images allows T1 measurements in more myocardial segments by reducing motion-induced T1 estimation errors in myocardial segments. Magn Reson Med, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Shiro Nakamori, Haisam Ismail, Long H Ngo, Warren J Manning, and Reza Nezafat. 2017. “Left ventricular geometry predicts ventricular tachyarrhythmia in patients with left ventricular systolic dysfunction: a comprehensive cardiovascular magnetic resonance study.” J Cardiovasc Magn Reson, 19, 1, Pp. 79.Abstract
BACKGROUND: Most patients with implantable cardioverter-defibrillator (ICD) implantation fail to utilize the device resulting in increasing societal costs and patient exposure to device morbidity. We sought to determine whether volumetric cardiovascular magnetic resonance (CMR) left ventricular (LV) spherical remodeling predicts future ventricular arrhythmias in primary ICD patients with reduced LV ejection fraction (EF). METHODS: Sixty-eight consecutive patients with transthoracic echocardiographic LVEF <35% referred for CMR prior to ICD implantation for primary prevention of sudden death were identified. Sphericity index was measured as the ratio of LV end-diastolic volume (from cine short axis stack) to the volume of a sphere with a LV end-diastolic 4-chamber length diameter. RESULTS: During a median follow-up of 55 months (interquartile range; 28-88), 15 patients (22%) received appropriate ICD therapy. Multivariable Cox's proportional hazard modeling identified increased CMR-derived sphericity index as the strongest independent predictor of appropriate ICD therapy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.02 to 1.16; p = 0.007). In addition, dichotomized volumetric CMR-derived sphericity index ≥0.57 carried a 4-fold hazard risk for appropriate ICD therapy, controlling for age and LVEF (HR, 4.49; 95% CI, 1.53 to 13.21; p = 0.006). When sphericity index, LVEF and mass index were used in combination, important incremental prognostic information was achieved (net reclassification improvement, 0.42; 95% CI, 0.06 to 0.77). CONCLUSIONS: The combined assessment of LV geometry, mass index and systolic function may provide incremental prognostic information regarding ventricular arrhythmia requiring appropriate ICD therapy in primary prevention patients with reduced LVEF.
Daniel R Messroghli, James C Moon, Vanessa M Ferreira, Lars Grosse-Wortmann, Taigang He, Peter Kellman, Julia Mascherbauer, Reza Nezafat, Michael Salerno, Erik B Schelbert, Andrew J Taylor, Richard Thompson, Martin Ugander, Ruud B van Heeswijk, and Matthias G Friedrich. 2017. “Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imagi.” J Cardiovasc Magn Reson, 19, 1, Pp. 75.Abstract
Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.
Alex Y Tan, Bruce D Nearing, Michael Rosenberg, Reza Nezafat, Mark E Josephson, and Richard L Verrier. 2017. “Interlead heterogeneity of R- and T-wave morphology in standard 12-lead ECGs predicts sustained ventricular tachycardia/fibrillation and arrhythmic death in patients with cardiomyopathy.” J Cardiovasc Electrophysiol, 28, 11, Pp. 1324-1333.Abstract
INTRODUCTION: Nonuniformities in depolarization and repolarization morphology are critical factors in ventricular arrhythmogenesis. METHODS AND RESULTS: We assessed interlead R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH) in standard 12-lead electrocardiograms (ECGs) using second central moment analysis. This technique quantifies variance about the mean morphology of beats in adjoining precordial leads, V4 , V5 , and V6 in this study. The study was conducted in 120 consecutive patients without an apparent reversible trigger for ventricular tachycardia (VT), recent myocardial infarction, or active ischemia, who presented for electrophysiologic study, implantable cardioverter defibrillator (ICD) placement, or generator change at our institution from 2008 to 2011. Primary outcome was sustained VT/ventricular fibrillation (VF) or appropriate ICD therapies. Secondary outcome was arrhythmic death or resuscitated cardiac arrest. Cutpoints for elevated RWH (>160 μV) and TWH (>80 μV) identified 67% of primary outcome cases and 85% of secondary outcome cases. Cardiomyopathy patients who met the primary outcome (n = 42) had significantly higher TWH than those who did not (n = 28) (TWH: 95 ± 11 μV vs. 44 ± 9 μV, P < 0.002). Likewise, cardiomyopathy patients who met secondary outcome (N = 13) had VT/VF during follow-up and also had significantly higher TWH than survivors (N = 57) (TWH: 105 ± 24 μV vs. 67 ± 8 μV, P < 0.002). Kaplan-Meier analysis revealed significant differences in arrhythmia-free survival (P = 0.012) and total survival (P = 0.011) among cardiomyopathy patients with (n = 37) compared to without (n = 33) elevated RWH and/or TWH independent of age, sex, and left ventricular ejection fraction (LVEF). CONCLUSION: Interlead RWH and TWH in 12-lead ECGs predict sustained ventricular arrhythmia, appropriate ICD therapies, and arrhythmic death or cardiac arrest in cardiomyopathy patients independent of LVEF and other standard variables.
Tamer A Basha, Mehmet Akçakaya, Charlene Liew, Connie W Tsao, Francesca N Delling, Gifty Addae, Long Ngo, Warren J Manning, and Reza Nezafat. 2017. “Clinical performance of high-resolution late gadolinium enhancement imaging with compressed sensing.” J Magn Reson Imaging, 46, 6, Pp. 1829-1838.Abstract
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 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1829-1838.
Shiro Nakamori, An H Bui, Jihye Jang, Hossam A El-Rewaidy, Shingo Kato, Long H Ngo, Mark E Josephson, Warren J Manning, and Reza Nezafat. 2017. “Increased myocardial native T1 relaxation time in patients with nonischemic dilated cardiomyopathy with complex ventricular arrhythmia.” J Magn Reson Imaging.Abstract
PURPOSE: To study the relationship between diffuse myocardial fibrosis and complex ventricular arrhythmias (ComVA) in patients with nonischemic dilated cardiomyopathy (NICM). We hypothesized that NICM patients with ComVA would have a higher native myocardial T1 time, suggesting more extensive myocardial diffuse fibrosis. MATERIALS AND METHODS: We prospectively enrolled NICM patients with a history of ComVA (n = 50) and age-matched NICM patients without ComVA (n = 57). Imaging was performed at 1.5T with a protocol that included cine magnetic resonance imaging (MRI) for left ventricular (LV) function, late gadolinium enhancement (LGE) for focal scar, and native T1 mapping for diffuse fibrosis assessment. RESULTS: Global native T1 time was significantly higher in patients with NICM with ComVA when compared to patients with NICM without ComVA (1131 ± 42 vs. 1107 ± 45 msec, P = 0.006), and this finding remained after excluding segments with scar on LGE (1124 ± 36 vs. 1102 ± 44 msec, P = 0.006). Native T1 was similar in NICM patients with and without the presence of LGE (1121 ± 39 vs. 1117 ± 48 msec, P = 0.68) and mildly correlated with LV end-diastolic volume index (r = 0.27, P = 0.005), LV end-systolic volume index (r = 0.24, P = 0.01), and LV ejection fraction (r = -0.28, P = 0.003). Native T1 value for each 10-msec increment was an independent predictor of ComVA (odds ratio 1.14, 95% confidence interval 1.03-1.25; P = 0.008) beyond LV function and LGE. CONCLUSION: NICM patients with ComVA have higher native T1 compared to NICM without any documented ComVA. Native myocardial T1 is independently associated with ComVA, after adjusting for LV function and LGE. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. In memoriam: The authors are grateful for Dr. Josephson's inspiring guidance and contributions to this study.
Shiro Nakamori, Javid Alakbarli, Steven Bellm, Shweta R Motiwala, Gifty Addae, Warren J Manning, and Reza Nezafat. 2017. “Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.” J Magn Reson Imaging, 46, 4, Pp. 1073-1081.Abstract
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 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081.
An H Bui, Sébastien Roujol, Murilo Foppa, Kraig V Kissinger, Beth Goddu, Thomas H Hauser, Peter J Zimetbaum, Long H Ngo, Warren J Manning, Reza Nezafat, and Francesca N Delling. 2017. “Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia.” Heart, 103, 3, Pp. 204-209.Abstract
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.
Tamer A Basha, Maxine C Tang, Connie Tsao, Cory M Tschabrunn, Elad Anter, Warren J Manning, and Reza Nezafat. 2017. “Improved dark blood late gadolinium enhancement (DB-LGE) imaging using an optimized joint inversion preparation and T2 magnetization preparation.” Magn Reson Med.Abstract
PURPOSE: To develop a dark blood-late gadolinium enhancement (DB-LGE) sequence that improves scar-blood contrast and delineation of scar region. METHODS: The DB-LGE sequence uses an inversion pulse followed by T2 magnetization preparation to suppress blood and normal myocardium. Time delays inserted after preparation pulses and T2 -magnetization-prep duration are used to adjust tissue contrast. Selection of these parameters was optimized using numerical simulations and phantom experiments. We evaluated DB-LGE in 9 swine and 42 patients (56 ± 14 years, 33 male). Improvement in scar-blood contrast and overall image quality was subjectively evaluated by two independent readers (1 = poor, 4 = excellent). The signal ratios among scar, blood, and myocardium were compared. RESULTS: Simulations and phantom studies demonstrated that simultaneous nulling of myocardium and blood can be achieved by selecting appropriate timing parameters. The scar-blood contrast score was significantly higher for DB-LGE (P < 0.001) with no significant difference in overall image quality (P > 0.05). Scar-blood signal ratios for DB-LGE versus LGE were 5.0 ± 2.8 versus 1.5 ± 0.5 (P < 0.001) for patients, and 2.2 ± 0.7 versus 1.0 ± 0.4 (P = 0.0023) for animals. Scar-myocardium signal ratios were 5.7 ± 2.9 versus 6.3 ± 2.6 (P = 0.35) for patients, and 3.7 ± 1.1 versus 4.1 ± 2.0 (P = 0.60) for swine. CONCLUSIONS: The DB-LGE sequence simultaneously reduces normal myocardium and blood signal intensity, thereby enhancing scar-blood contrast while preserving scar-myocardium contrast. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Gabriella Captur, Peter Gatehouse, Kathryn E Keenan, Friso G Heslinga, Ruediger Bruehl, Marcel Prothmann, Martin J Graves, Richard J Eames, Camilla Torlasco, Giulia Benedetti, Jacqueline Donovan, Bernd Ittermann, Redha Boubertakh, Andrew Bathgate, Celine Royet, Wenjie Pang, Reza Nezafat, Michael Salerno, Peter Kellman, and James C Moon. 2016. “A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance-the T1 Mapping and ECV Standardization in cardiovascular magnetic resonance (T1MES) program.” J Cardiovasc Magn Reson, 18, 1, Pp. 58.Abstract
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.
Mehmet Akçakaya, Sebastian Weingärtner, Tamer A Basha, Sébastien Roujol, Steven Bellm, and Reza Nezafat. 2016. “Joint myocardial T1 and T2 mapping using a combination of saturation recovery and T2 -preparation.” Magn Reson Med, 76, 3, Pp. 888-96.Abstract
PURPOSE: To develop a heart-rate independent breath-held joint T1 -T2 mapping sequence for accurate simultaneous estimation of coregistered myocardial T1 and T2 maps. METHODS: A novel preparation scheme combining both a saturation pulse and T2 -preparation in a single R-R interval is introduced. The time between these two pulses, as well as the duration of the T2 -preparation is varied in each heartbeat, acquiring images with different T1 and T2 weightings, and no magnetization dependence on previous images. Inherently coregistered T1 and T2 maps are calculated from these images. Phantom imaging is performed to compare the proposed maps with spin echo references. In vivo imaging is performed in ten subjects, comparing the accuracy and precision of the proposed technique to existing myocardial T1 and T2 mapping sequences of the same duration. RESULTS: Phantom experiments show that the proposed technique provides accurate quantification of T1 and T2 values over a wide-range (T1 : 260 ms to 1460 ms, T2 : 40 ms to 200 ms). In vivo imaging shows that the proposed sequence quantifies T1 and T2 values similar to a saturation-based T1 mapping and a conventional breath-hold T2 mapping sequence, respectively. CONCLUSION: The proposed sequence allows joint estimation of accurate and coregistered quantitative myocardial T1 and T2 maps in a single breath-hold. Magn Reson Med 76:888-896, 2016. © 2015 Wiley Periodicals, Inc.
Shingo Kato, Shiro Nakamori, Steven Bellm, Jihye Jang, Tamer Basha, Martin Maron, Warren J Manning, and Reza Nezafat. 2016. “Myocardial Native T1 Time in Patients With Hypertrophic Cardiomyopathy.” Am J Cardiol, 118, 7, Pp. 1057-62.Abstract
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.
Jihye Jang, Steven Bellm, Sébastien Roujol, Tamer A Basha, Maryam Nezafat, Shingo Kato, Sebastian Weingärtner, and Reza Nezafat. 2016. “Comparison of spoiled gradient echo and steady-state free-precession imaging for native myocardial T1 mapping using the slice-interleaved T1 mapping (STONE) sequence.” NMR Biomed, 29, 10, Pp. 1486-96.Abstract
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.
Shingo Kato, Shiro Nakamori, Sébastien Roujol, Francesca N Delling, Shadi Akhtari, Jihye Jang, Tamer Basha, Sophie Berg, Kraig V Kissinger, Beth Goddu, Warren J Manning, and Reza Nezafat. 2016. “Relationship between native papillary muscle T1 time and severity of functional mitral regurgitation in patients with non-ischemic dilated cardiomyopathy.” J Cardiovasc Magn Reson, 18, 1, Pp. 79.Abstract
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.
Steven Bellm, Tamer A Basha, Ravi V Shah, Venkatesh L Murthy, Charlene Liew, Maxine Tang, Long H Ngo, Warren J Manning, and Reza Nezafat. 2016. “Reproducibility of myocardial T1 and T2 relaxation time measurement using slice-interleaved T1 and T2 mapping sequences.” J Magn Reson Imaging, 44, 5, Pp. 1159-1167.Abstract
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.
Cory M Tschabrunn, Sebastien Roujol, Nicole C Dorman, Reza Nezafat, Mark E Josephson, and Elad Anter. 2016. “High-Resolution Mapping of Ventricular Scar: Comparison Between Single and Multielectrode Catheters.” Circ Arrhythm Electrophysiol, 9, 6.Abstract
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.
Ravi V Shah, Shingo Kato, Sebastien Roujol, Venkatesh Murthy, Steven Bellm, Abyaad Kashem, Tamer Basha, Jihye Jang, Aaron S Eisman, Warren J Manning, and Reza Nezafat. 2016. “Native Myocardial T1 as a Biomarker of Cardiac Structure in Non-Ischemic Cardiomyopathy.” Am J Cardiol, 117, 2, Pp. 282-8.Abstract
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.
Shingo Kato, Murilo Foppa, Sébastien Roujol, Tamer Basha, Sophie Berg, Kraig V Kissinger, Beth Goddu, Warren J Manning, and Reza Nezafat. 2016. “Left ventricular native T1 time and the risk of atrial fibrillation recurrence after pulmonary vein isolation in patients with paroxysmal atrial fibrillation.” Int J Cardiol, 203, Pp. 848-54.Abstract
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.
Cory M Tschabrunn, Sébastien Roujol, Reza Nezafat, Beverly Faulkner-Jones, Alfred E Buxton, Mark E Josephson, and Elad Anter. 2016. “A swine model of infarct-related reentrant ventricular tachycardia: Electroanatomic, magnetic resonance, and histopathological characterization.” Heart Rhythm, 13, 1, Pp. 262-73.Abstract
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.
Tamer A Basha, Steven Bellm, Sébastien Roujol, Shingo Kato, and Reza Nezafat. 2016. “Free-breathing slice-interleaved myocardial T2 mapping with slice-selective T2 magnetization preparation.” Magn Reson Med, 76, 2, Pp. 555-65.Abstract
PURPOSE: To develop and evaluate a free-breathing slice-interleaved T2 mapping sequence by proposing a new slice-selective T2 magnetization preparation (T2 prep) sequence that allows interleaved data acquisition for different slices in subsequent heartbeats. METHODS: We developed a slice-selective T2 prep for myocardial T2 mapping by adding slice-selective gradients to a conventional single-slice T2 prep sequence. In this sequence, five slices are acquired during five consecutive heartbeats, each using a slice-selective T2 prep. The scheme was repeated four times using different T2 prep echo times. We compared the performance of the proposed slice-interleaved T2 mapping sequence and the conventional single-slice T2 mapping sequence in term of accuracy, precision, and reproducibility using phantom experiments and in vivo imaging in 10 healthy subjects. We also evaluated the feasibility of the proposed sequence in 28 patients with cardiovascular disease, and the quality of the maps was scored subjectively. Furthermore, we investigated the impact of through-plane motion by comparing T2 measurements acquired during end-systole versus mid-diastole. RESULTS: T2 measurements using a slice-interleaved T2 mapping sequence were correlated with a spin echo (r(2)  = 0.88) and single-slice T2 mapping sequence (r(2)  = 0.98). The mean myocardial T2 values were correlated between slice-interleaved (48 ms) and single-slice (51 ms) T2 mapping sequences. Subjective scores of T2 map quality were good to excellent in 81% of the maps in patients. There was no difference in T2 measurements between end-systole versus mid-diastole. CONCLUSIONS: The proposed free-breathing slice-interleaved T2 mapping sequence allows T2 measurements of five left ventricular slices in 20 heartbeats with similar reproducibility and precision as the single-slice T2 mapping sequence but with a four-fold reduction in acquisition time. Magn Reson Med 76:555-565, 2016. © 2015 Wiley Periodicals, Inc.
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