Nakamori S, Fahmy A, Jang J, El-Rewaidy H, Neisius U, Berg S, Goddu B, Pierce P, Rodriguez J, Hauser T, Ngo LH, Manning WJ, Nezafat R. Changes in Myocardial Native T1 and T2 After Exercise Stress: A Noncontrast CMR Pilot Study. JACC: Cardiovascular Imaging 2019;Abstract


This study assessed changes in myocardial native T1 and T2 values after supine exercise stress in healthy subjects and in patients with suspected ischemia as potential imaging markers of ischemia.


With emerging data on the long-term retention of gadolinium in the body and brain, there is a need for an alternative noncontrast cardiovascular magnetic resonance (CMR)-based myocardial ischemia assessment.


Twenty-eight healthy adult subjects and 14 patients with coronary artery disease (CAD) referred for exercise stress and/or rest single-photon emission computed tomography/myocardial perfusion imaging (SPECT/MPI) for evaluation of chest pain were prospectively enrolled. Free-breathing myocardial native T1 and T2 mapping were performed before and after supine bicycle exercise stress using a CMR-compatible supine ergometer positioned on the MR table. Differences in T1 rest, T2 rest and T1 post-exercise, T2 post-exercise values were calculated as T1 and T2 reactivity, respectively.


The mean exercise intensity was 104 W, with exercise duration of 6 to 12 min. After exercise, native T1 was increased in healthy subjects (p < 0.001). T1 reactivity, but not T2 reactivity, correlated with the rate-pressure product as the index of myocardial blood flow during exercise (r = 0.62; p < 0.001). In patients with CAD, T1 reactivity was associated with the severity of myocardial perfusion abnormality on SPECT/MPI (normal: 4.9%; quartiles: 3.7% to 6.3%, mild defect: 1.2%, quartiles: 0.08% to 2.5%; moderate defect: 0.45%, quartiles: -0.35% to 1.4%; severe defect: 0.35%, quartiles: -0.44% to 0.8%) and had similar potential as SPECT/MPI to detect significant CAD (>50% diameter stenosis on coronary angiography). The area under the receiver-operating characteristic curve was 0.80 versus 0.72 (p = 0.40). The optimum cutoff value of T1 reactivity for predicting flow-limiting stenosis was 2.5%, with a sensitivity of 83% and a specificity of 92%, a negative predictive value of 96%, a positive predictive value of 71%, and an area under the curve of 0.86.


Free-breathing stress/rest native T1 mapping, but not T2 mapping, can detect physiological changes in the myocardium during exercise. Our feasibility study in patients shows the potential of this technique as a method for detecting myocardial ischemia in patients with CAD without using a pharmacological stress agent.

Jang J, Hwang H-J, Tschabrunn CM, Whitaker J, Menze B, Anter E, Nezafat R. Cardiovascular Magnetic Resonance-Based Three-Dimensional Structural Modeling and Heterogeneous Tissue Channel Detection in Ventricular Arrhythmia. Scientific Reports 2019;9(9317)Abstract


Geometrical structure of the myocardium plays an important role in understanding the generation of

arrhythmias. In particular, a heterogeneous tissue (HT) channel defined in cardiovascular magnetic

resonance (CMR) has been suggested to correlate with conduction channels defined in electroanatomic

mapping in ventricular tachycardia (VT). Despite the potential of CMR for characterization of the

arrhythmogenic substrate, there is currently no standard approach to identify potential conduction

channels. Therefore, we sought to develop a workflow to identify HT channel based on the structural

3D modeling of the viable myocardium within areas of dense scar. We focus on macro-level HT channel

detection in this work. The proposed technique was tested in high-resolution ex-vivo CMR images in 20

post-infarct swine models who underwent an electrophysiology study for VT inducibility. HT channel

was detected in 15 animals with inducible VT, whereas it was only detected in 1 out of 5 animal with

non-inducible VT (P < 0.01, Fisher’s exact test). The HT channel detected in the non-inducible animal

was shorter than those detected in animals with inducible VTs (inducible-VT animals: 35 ± 14 mm vs.

non-inducible VT animal: 9.94 mm). Electrophysiology study and histopathological analyses validated

the detected HT channels. The proposed technique may provide new insights for understanding the

macro-level VT mechanism.

Jang J, Whitaker J, Leshem E, Ngo LH, Neisius U, Nakamori S, Pashakhanloo F, Menze B, Manning WJ, Anter E, Nezafat R. Local Conduction Velocity in the Presence of Late Gadolinium Enhancement and Myocardial Wall Thinning: A Cardiac Magnetic Resonance Study in a Swine Model of Healed Left Ventricular Infarction. Circulation: Arrhythmia and Electrophysiology 2019;12(5)Abstract


Conduction velocity (CV) is an important property that contributes to the arrhythmogenicity of the tissue substrate. The aim of this study was to investigate the association between local CV versus late gadolinium enhancement (LGE) and myocardial wall thickness in a swine model of healed left ventricular infarction.


Six swine with healed myocardial infarction underwent cardiovascular magnetic resonance imaging and electroanatomic mapping. Two healthy controls (one treated with amiodarone and one unmedicated) underwent electroanatomic mapping with identical protocols to establish the baseline CV. CV was estimated using a triangulation technique. LGE+ regions were defined as signal intensity >2 SD than the mean of remote regions, wall thinning+ as those with wall thickness <2 SD than the mean of remote regions. LGE heterogeneity
was defined as SD of LGE in the local neighborhood of 5 mm and wall thickness gradient as SD within 5 mm. Cardiovascular magnetic resonance and electroanatomic mapping data were registered, and hierarchical modeling was performed to estimate the mean difference of CV (LGE+/−, wall thinning+/−), or the change of the mean of CV per unit change (LGE heterogeneity, wall thickness gradient).


Significantly slower CV was observed in LGE+ (0.33±0.25 versus 0.54±0.36 m/s; P<0.001) and wall thinning+ regions (0.38±0.28 versus 0.55±0.37 m/s; P<0.001). Areas with greater LGE heterogeneity (P<0.001) and wall thickness gradient (P<0.001) exhibited slower CV.


Slower CV is observed in the presence of LGE, myocardial wall thinning, high LGE heterogeneity, and a high wall thickness gradient. Cardiovascular magnetic resonance may offer a valuable imaging surrogate for estimating CV, which may support noninvasive identification of the arrhythmogenic substrate.

Neisius U, El-Rewaidy H, Nakamori S, Rodriguez J, Manning WJ, Nezafat R. Radiomic Analysis of Myocardial Native T1 Imaging Discriminates Between Hypertensive Heart Disease and Hypertrophic Cardiomyopathy. JACC: Cardiovascular Imaging 2019;Abstract


This study sought to examine the diagnostic ability of radiomic texture analysis (TA) on quantitative cardiovascular magnetic resonance images to differentiate between hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM).


HHD and HCM are associated with increased left ventricular wall thickness (LVWT). Contemporary guidelines define HCM as LVWT ≥15 mm that is unexplained by other disease, which complicates diagnosis in cases of co-occurrences. Conventional global native T1 mapping involves calculation of mean T1 values as a surrogate for fibrosis. However, there may be differences in its spatial localization, such as diffuse and more focal fibrosis in HHD and HCM, respectively.


This study identified 232 subjects (53 with HHD, 108 with HCM, and 71 control subjects) for TA who consecutively underwent free-breathing multislice native T1 mapping. Four sets of texture descriptors were applied to capture spatially dependent and independent pixel statistics. Six texture features were sequentially selected with the best discriminatory capacity between HHD and HCM and were tested using a support vector machine (SVM) classifier. Each disease group was randomly split 4:1 (feature selection/test validation), in which the reproducibility of the pattern was analyzed in the test validation dataset.


The selected texture features provided the maximum diagnostic accuracy of 86.2% (c-statistic: 0.820; 95% confidence interval [CI]: 0.769 to 0.903) using the SVM. For the test validation dataset, the accuracy of the pattern remained high at 80.0% (c-statistic: 0.89; 95% CI: 0.77 to 1.00). Global native T1, with an accuracy of 64%, separated HHD and HCM patients modestly (c-statistic: 0.549; 95% CI: 0.452 to 0.640).


Radiomics analysis of native T1 images discriminates between HHD and HCM patients and provides incremental value over global native T1 mapping.

Fahmy AS, El-Rewaidy H, Nezafat M, Nakamori S, Nezafat R. Automated analysis of cardiovascular magnetic resonance myocardial native T1 mapping images using fully convolutional neural networks. Journal of Cardiovascular Magnetic Resonance 2019;21(1)Abstract


Cardiovascular magnetic resonance (CMR) myocardial native T1 mapping allows assessment of interstitial diffuse fibrosis. In this technique, the global and regional T1 are measured manually by drawing region of interest in motion-corrected T1 maps. The manual analysis contributes to an already lengthy CMR analysis workflow and impacts measurements reproducibility. In this study, we propose an automated method for combined myocardium segmentation, alignment, and T1 calculation for myocardial T1 mapping.


A deep fully convolutional neural network (FCN) was used for myocardium segmentation in T1 weighted images. The segmented myocardium was then resampled on a polar grid, whose origin is located at the center-of-mass of the segmented myocardium. Myocardium T1 maps were reconstructed from the resampled T1 weighted images using curve fitting. The FCN was trained and tested using manually segmented images for 210 patients (5 slices, 11 inversion times per patient). An additional image dataset for 455 patients (5 slices and 11 inversion times per patient), analyzed by an expert reader using a semi-automatic tool, was used to validate the automatically calculated global and regional T1 values. Bland-Altman analysis, Pearson correlation coefficient, r, and the Dice similarity coefficient (DSC) were used to evaluate the performance of the FCN-based analysis on per-patient and per-slice basis. Inter-observer variability was assessed using intraclass correlation coefficient (ICC) of the T1 values calculated by the FCN-based automatic method and two readers.


The FCN achieved fast segmentation (< 0.3 s/image) with high DSC (0.85 ± 0.07). The automatically and manually calculated T1 values (1091 ± 59 ms and 1089 ± 59 ms, respectively) were highly correlated in per-patient (r = 0.82; slope = 1.01; p < 0.0001) and per-slice (r = 0.72; slope = 1.01; p < 0.0001) analyses. Bland-Altman analysis showed good agreement between the automated and manual measurements with 95% of measurements within the limits-of-agreement in both per-patient and per-slice analyses. The intraclass correllation of the T1 calculations by the automatic method vs reader 1 and reader 2 was respectively 0.86/0.56 and 0.74/0.49 in the per-patient/per-slice analyses, which were comparable to that between two expert readers (=0.72/0.58 in per-patient/per-slice analyses).


The proposed FCN-based image processing platform allows fast and automatic analysis of myocardial native T1 mapping images mitigating the burden and observer-related variability of manual analysis.


Automatic analysis; Convolutional neural networks; Myocardium segmentation; T1 mapping

Duan C, Zhu Y, Jang J, Rodriguez J, Neisius U, Fahmy AS, Nezafat R. Non-contrast myocardial infarct scar assessment using a hybrid native T1 and magnetization transfer imaging sequence at 1.5T. Magnetic Resonance in Medicine 2018;00:1-10.Abstract


To develop a gadolinium-free cardiac MR technique that simultaneously exploits native T1 and magnetization transfer (MT) contrast for the imaging of myocardial infarction.


A novel hybrid T one and magnetization transfer (HYTOM) method was developed based on the modified look-locker inversion recovery (MOLLI) sequence, with a train of MT-prep pulses placed before the balanced SSFP (bSSFP) readout pulses. Numerical simulations, based on Bloch-McConnell equations, were performed to investigate the effects of MT induced by (1) the bSSFP readout pulses, and (2) the MT-prep pulses, on the measured, "apparent," native T1 values. The HYTOM method was then tested on 8 healthy adult subjects, 6 patients, and a swine with prior myocardial infarction (MI). The resulting imaging contrast between normal myocardium and infarcted tissues was compared with that of MOLLI. Late gadolinium enhancement (LGE) images were also obtained for infarct assessment in patients and swine.


Numerical simulation and in vivo studies in healthy volunteers demonstrated that MT effects, resulting from on-resonance bSSFP excitation pulses and off-resonance MT-prep pulses, reduce the measured T1 in both MOLLI and HTYOM. In vivo studies in patients and swine showed that the HYTOM sequence can identify locations of MI, as seen on LGE. Furthermore, the HYTOM method yields higher myocardium-to-scar contrast than MOLLI (contrast-to-noise ratio: 7.33 ± 1.67 vs. 3.77 ± 0.66, P < 0.01).


The proposed HYTOM method simultaneously exploits native T1 and MT contrast and significantly boosts the imaging contrast for myocardial infarction.


Bloch-McConnell equations; MOLLI; magnetization transfer; myocardial infarction; native T1

Zhu Y, Kang J, Duan C, Nezafat M, Neisius U, Jang J, Nezafat R. Integrated motion correction and dictionary learning for free-breathing myocardial T1 mapping. 2018;Abstract


To develop and evaluate an integrated motion correction and dictionary learning (MoDic) technique to accelerate data acquisition for myocardial T1 mapping with improved accuracy.


MoDic integrates motion correction with dictionary learning-based reconstruction. A random undersampling scheme was implemented for slice-interleaved T1 mapping sequence to allow prospective undersampled data acquisition. Phantom experiments were performed to evaluate the effect of reconstruction on T1 measurement. In vivo T1 mappings were acquired in 8 healthy subjects using 6 different acceleration approaches: uniform or randomly undersampled k-space data with reduction factors (R) of 2, 3, and 4. Uniform undersampled data were reconstructed with SENSE, and randomly undersampled k-space data were reconstructed using dictionary learning, compressed sensing SENSE, and MoDic methods. Three expert readers subjectively evaluated the quality of T1 maps using a 4-point scoring system. The agreement between T1 values was assessed by Bland-Altman analysis.


In the phantom study, the accuracy of T1 measurements improved with increasing reduction factors ( − 31 ± 35 ms, − 13 ± 18 ms, and − 5 ± 11 ms for reduction factor (R) = 2 to 4, respectively). The image quality of in vivo T1 maps assessed by subjective scoring using MoDic was similar to that of SENSE at R = 2 (P = .61) but improved at R = 3 and 4 (P < .01). The scores of dictionary learning (2.98 ± 0.71, 2.91 ± 0.60, and 2.67 ± 0.71 for R = 2 to 4) and CS-SENSE (3.32 ± 0.42, 3.05 ± 0.43, and 2.53 ± 0.43) were lower than those of MoDic (3.48 ± 0.46, 3.38 ± 0.52, and 2.9 ± 0.60) for all reduction factors (P < .05 for all).


The MoDic method accelerates data acquisition for myocardial T1 mapping with improved T1 measurement accuracy.


compressed sensing; dictionary learning; motion correction; myocardial T1 mapping

Nakamori S, Ngo LH, Tugal D, Manning WJ, Nezafat R. Incremental Value of Left Atrial Geometric Remodeling in Predicting Late Atrial Fibrillation Recurrence After Pulmonary Vein Isolation: A Cardiovascular Magnetic Resonance Study. J Am Heart Assoc. 2018;7(19)Abstract


Left atrial ( LA ) enlargement is a marker for increased risk of atrial fibrillation ( AF ). However, LA remodeling is a complex process that is poorly understood, and LA geometric remodeling may also be associated with the development of AF . We sought to determine whether LA spherical remodeling or its temporal change predict late AF recurrence after pulmonary vein isolation ( PVI ).


Two hundred twenty-seven consecutive patients scheduled for their first PVI for paroxysmal or persistent AF who underwent cardiovascular magnetic resonance before and within 6 months after PVI were retrospectively identified. The LA sphericity index was computed as the ratio of the measured LA maximum volume to the volume of a sphere with maximum LA length diameter. During mean follow-up of 25 months, 88 patients (39%) experienced late recurrence of AF. Multivariable Cox regression analyses identified an increased pre- PVI LA sphericity index as an independent predictor of late AF recurrence (hazard ratio, 1.32; 95% confidence interval, 1.07-1.62, P=0.009). Patients in the highest LA sphericity index tertile were at highest risk of late recurrence (highest versus lowest: 59% versus 28%; P<0.001). The integration of the LA sphericity index to the LA minimum volume index and passive emptying fraction provided important incremental prognostic information for predicting late AF recurrence post PVI (categorical net reclassification improvement, 0.43; 95% confidence interval, 0.16-0.69, P=0.001).


The assessment of pre- PVI LA geometric remodeling provides incremental prognostic information regarding late AF recurrence and may be useful to identify those for whom PVI has reduced success or for whom more aggressive ablation or medications may be useful.


atrial fibrillation; cardiovascular magnetic resonance; late recurrence; left atrial sphericity index; left atrial volume; pulmonary vein isolation

Jang J, Tschabrunn CM, Barkagan M, Anter E, Menze B, Nezafat R. Three-dimensional holographic visualization of high-resolution myocardial scar on HoloLens. PLos One 2018;13(10)Abstract
Visualization of the complex 3D architecture of myocardial scar could improve guidance of radio-frequency ablation in the treatment of ventricular tachycardia (VT). In this study, we sought to develop a framework for 3D holographic visualization of myocardial scar, imaged using late gadolinium enhancement (LGE), on the augmented reality HoloLens. 3D holographic LGE model was built using the high-resolution 3D LGE image. Smooth endo/epicardial surface meshes were generated using Poisson surface reconstruction. For voxel-wise 3D scar model, every scarred voxel was rendered into a cube which carries the actual resolution of the LGE sequence. For surface scar model, scar information was projected on the endocardial surface mesh. Rendered layers were blended with different transparency and color, and visualized on HoloLens. A pilot animal study was performed where 3D holographic visualization of the scar was performed in 5 swines who underwent controlled infarction and electroanatomic mapping to identify VT substrate. 3D holographic visualization enabled assessment of the complex 3D scar architecture with touchless interaction in a sterile environment. Endoscopic view allowed visualization of scar from the ventricular chambers. Upon completion of the animal study, operator and mapping specialist independently completed the perceived usefulness questionnaire in the six-item usefulness scale. Operator and mapping specialist found it useful (usefulness rating: operator, 5.8; mapping specialist, 5.5; 1-7 scale) to have scar information during the intervention. HoloLens 3D LGE provides a true 3D perception of the complex scar architecture with immersive experience to visualize scar in an interactive and interpretable 3D approach, which may facilitate MR-guided VT ablation.
Akhtari S, Chuang ML, Salton CJ, Berg S, Kissinger KV, Goddu B, O'Donnell CJ, Manning WJ. Effect of isolated left bundle-branch block on biventricular volumes and ejection fraction: a cardiovascular magnetic resonance assessment. J Cardiovasc Magn Reson 2018;20(66)Abstract


Left bundle branch block (LBBB) is associated with abnormal left ventricular (LV) contraction, and is frequently associated with co-morbid cardiovascular disease, but the effect of an isolated (i.e. in the absence of cardiovascular dissease) LBBB on biventricular volumes and ejection fraction (EF) is not well characterized. The objective of this study was to compare LV and right ventricular (RV) volumes and EF in adults with an isolated LBBB to matched healthy controls and to population-derived normative values, using cardiovascular magnetic resonance (CMR) imaging.


We reviewed our clinical echocardiography database and the Framingham Heart Study Offspring cohort CMR database to identify adults with an isolated LBBB. Age-, sex-, hypertension-status, and body-surface area (BSA)-matched controls were identified from the Offspring cohort. All study subjects were scanned using the same CMR hardware and imaging sequence. Isolated-LBBB cases were compared with matched controls using Wilcoxon paired signed-rank test, and to normative reference values via Z-score.


Isolated-LBBB subjects (n = 18, 10F) ranged in age from 37 to 82 years. An isolated LBBB was associated with larger LV end-diastolic and end-systolic volumes (both p < 0.01) and lower LVEF (56+/- 7% vs. 68+/- 6%; p  <0.001) with similar myocardial contraction fraction. LVEF in isolated LBBB was nearly two standard deviations (Z = - 1.95) below mean sex and age-matched group values. LV stroke volume, cardiac output, and mass, and all RV parameters were similar (p = NS) between the groups.


Adults with an isolated LBBB have greater LV volumes and markedly reduced LVEF, despite the absence of overt cardiovascular disease. These data may be useful toward the clinical interpretation of imaging studies performed on patients with an isolated LBBB.

Choi S, Han SI, Jung D, Hwang HJ, Lim C, Bae S, Park OK, Tschabrunn CM, Lee M, Bae SY, Yu JW, Ryu JH, Lee S-W, Park K, Kang PM, Lee WB, Nezafat R, Hyeon T, Kim D-H. Highly conductive, stretchable and biocompatible Ag-Au core-sheath nanowire composite for wearable and implantable bioelectronics [Internet]. Nature Nanotechnology 2018; Publisher's VersionAbstract
Wearable and implantable devices require conductive, stretchable and biocompatible materials. However, obtaining composites that simultaneously fulfil these requirements is challenging due to a trade-off between conductivity and stretchability. Here, we report on Ag–Au nanocomposites composed of ultralong gold-coated silver nanowires in an elastomeric block-copolymer matrix. Owing to the high aspect ratio and percolation network of the Ag–Au nanowires, the nanocomposites exhibit an optimized conductivity of 41,850 S cm−1 (maximum of 72,600 S cm−1). Phase separation in the Ag–Au nanocomposite during the solvent-drying process generates a microstructure that yields an optimized stretchability of 266% (maximum of 840%). The thick gold sheath deposited on the silver nanowire surface prevents oxidation and silver ion leaching, making the composite biocompatible and highly conductive. Using the nanocomposite, we successfully fabricate wearable and implantable soft bioelectronic devices that can be conformally integrated with human skin and swine heart for continuous electrophysiological recording, and electrical and thermal stimulation.
Nakamori S, Nezafat M, Ngo LH, Manning WJ, Nezafat R. Left Atrial Epicardial Fat Volume Is Associated With Atrial Fibrillation: A Prospective Cardiovascular Magnetic Resonance 3D Dixon Study. J Am Heart Assoc 2018;7(6)Abstract
BACKGROUND: Recent studies demonstrated a strong association between atrial fibrillation (AF) and epicardial fat around the left atrium (LA). We sought to assess whether epicardial fat volume around the LA is associated with AF, and to determine the additive value of LA-epicardial fat measurements to LA structural remodeling for identifying patients with AF using 3-dimensional multi-echo Dixon fat-water separated cardiovascular magnetic resonance. METHODS AND RESULTS: A total of 105 subjects were studied: 53 patients with a history of AF and 52 age-matched patients with other cardiovascular diseases but no history of AF. The 3-dimensional multi-echo Dixon fat-water separated sequence was performed for LA-epicardial fat measurements. AF patients had significantly greater LA-epicardial fat (28.9±12.3 and 14.2±7.3 mL for AF and non-AF, respectively; <0.001) and LA volume (110.8±38.2 and 89.7±30.3 mL for AF and non-AF, respectively; =0.002). LA-epicardial fat adjusted for LA volume was still higher in patients with AF compared with those without AF (<0.001). LA-epicardial fat and hypertension were independently associated with the risk of AF (odds ratio, 1.17; 95% confidence interval, 1.10%-1.25%, <0.001, and odds ratio, 3.29; 95% confidence interval, 1.17%-9.27%, =0.03, respectively). In multivariable logistic regression analysis adjusted for body surface area, LA-epicardial fat remained significant and an increase per mL was associated with a 42% increase in the odds of AF presence (odds ratio, 1.42; 95% confidence interval, 1.23%-1.62%, <0.001). Combined assessment of LA-epicardial fat and LA volume provided greater discriminatory performance for detecting AF than LA volume alone (c-statistic=0.88 and 0.74, respectively, DeLong test; <0.001). CONCLUSIONS: Cardiovascular magnetic resonance 3-dimensional Dixon-based LA-epicardial fat volume is significantly increased in AF patients. LA-epicardial fat measured by 3-dimensional Dixon provides greater performance for detecting AF beyond LA structural remodeling.
Wang C, Jang J, Neisius U, Nezafat M, Fahmy A, Kang J, Rodriguez J, Goddu B, Pierce P, Berg S, Zhang J, Wang X, Nezafat R. Black blood myocardial T2 mapping. Magn Reson Med 2018;Abstract
PURPOSE: To develop a black blood heart-rate adaptive T -prepared balanced steady-state free-precession (BEATS) sequence for myocardial T mapping. METHODS: In BEATS, blood suppression is achieved by using a combination of preexcitation and double inversion recovery pulses. The timing and flip angles of the preexcitation pulse are auto-calculated in each patient based on heart rate. Numerical simulations, phantom studies, and in vivo studies were conducted to evaluate the performance of BEATS. BEATS T maps were acquired in 36 patients referred for clinical cardiac MRI and in 1 swine with recent myocardial infarction. Two readers assessed all images acquired in patients to identify the presence of artifacts associated with slow blood flow. RESULTS: Phantom experiments showed that the BEATS sequence provided accurate T values over a wide range of simulated heart rates. Black blood myocardial T maps were successfully obtained in all subjects. No significant difference was found between the average T measurements obtained from the BEATS and conventional bright-blood T ; however, there was a decrease in precision using the BEATS sequence. A suppression of the blood pool resulted in sharper definition of the blood-myocardium border and reduced partial voluming effect. The subjective assessment showed that 16% (18 out of 108) of short-axis slices have residual blood artifacts (12 in the apical slice, 4 in the midventricular slice, and 2 in the basal slice). CONCLUSION: The BEATS sequence yields dark blood myocardial T maps with better definition of the blood-myocardium border. Further studies are warranted to evaluate diagnostic accuracy of black blood T mapping.
Hosny A, Keating SJ, Dilley JD, Ripley B, Kelil T, Pieper S, Kolb D, Bader C, Pobloth A-M, Griffin M, Nezafat R, Duda G, Chiocca EA, Stone JR, Michaelson JS, Dean MN, Oxman N, Weaver JC. From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets [Internet]. 3D Printing and Additive Manufacturing 2018;5(2) Publisher's VersionAbstract
Three-dimensional (3D) printing technologies are increasingly used to convert medical imaging studies into tangible (physical) models of individual patient anatomy, allowing physicians, scientists, and patients an unprecedented level of interaction with medical data. To date, virtually all 3D-printable medical data sets are created using traditional image thresholding, subsequent isosurface extraction, and the generation of .stl surface mesh file formats. These existing methods, however, are highly prone to segmentation artifacts that either over or underexaggerate the features of interest, thus resulting in anatomically inaccurate 3D prints. In addition, they often omit finer detailed structures and require time- and labor-intensive processes to visually verify their accuracy. To circumvent these problems, we present a bitmap-based multimaterial 3D printing workflow for the rapid and highly accurate generation of physical models directly from volumetric data stacks. This workflow employs a thresholding-free approach that bypasses both isosurface creation and traditional mesh slicing algorithms, hence significantly improving speed and accuracy of model creation. In addition, using preprocessed binary bitmap slices as input to multimaterial 3D printers allows for the physical rendering of functional gradients native to volumetric data sets, such as stiffness and opacity, opening the door for the production of biomechanically accurate models.
Fahmy AS, Neisius U, Tsao C, Berg S, Goddu E, Pierce P, Basha T, Ngo L, Manning WJ, Nezafat R. Gray blood late gadolinium enhancement cardiovascular magnetic resonance for improved detection of myocardial scar. J Cardiovasc Magn Reson 2018;Abstract


Low scar-to-blood contrast in late gadolinium enhanced (LGE) MRI limits the visualization of scars adjacent to the blood pool. Nulling the blood signal improves scar detection but results in lack of contrast between myocardium and blood, which makes clinical evaluation of LGE images more difficult.


GB-LGE contrast is achieved through partial suppression of the blood signal using T2magnetization preparation between the inversion pulse and acquisition. The timing parameters of GB-LGE sequence are determined by optimizing a cost-function representing the desired tissue contrast. The proposed 3D GB-LGE sequence was evaluated using phantoms, human subjects (n = 45) and a swine model of myocardial infarction (n = 5). Two independent readers subjectively evaluated the image quality and ability to identify and localize scarring in GB-LGE compared to black-blood LGE (BB-LGE) (i.e., with complete blood nulling) and conventional (bright-blood) LGE.


GB-LGE contrast was successfully generated in phantoms and all in-vivo scans. The scar-to-blood contrast was improved in GB-LGE compared to conventional LGE in humans (1.1 ± 0.5 vs. 0.6 ± 0.4, P < 0.001) and in animals (1.5 ± 0.2 vs. -0.03 ± 0.2). In patients, GB-LGE detected more tissue scarring compared to BB-LGE and conventional LGE. The subjective scores of the GB-LGE ability for localizing LV scar and detecting papillary scar were improved as compared with both BB-LGE (P < 0.024) and conventional LGE (P < 0.001). In the swine infarction model, GB-LGE scores for the ability to localize LV scar scores were consistently higher than those of both BB-LGE and conventional-LGE.


GB-LGE imaging improves the ability to identify and localize myocardial scarring compared to both BB-LGE and conventional LGE. Further studies are warranted to histologically validate GB-LGE.

Whitaker J, Tschabrunn CM, Jang J, Eran L, O'Neill M, Manning WJ, Anter E, Reza N. Cardiac MR Characterization of left ventricular remodeling in a swine model of infarct followed by reperfusion. J Magn Reson Imaging 2018;Abstract


Myocardial infarction (MI) survivors are at risk of complications including heart failure and malignant arrhythmias.


We undertook serial imaging of swine following MI with the aim of characterizing the longitudinal left ventricular (LV) remodeling in a translational model of ischemia-reperfusion-mediated MI.


Eight Yorkshire swine underwent mid left anterior descending coronary artery balloon occlusion to create an ischemia-reperfusion experimental model of MI.


1.5T Philips Achieva scanner. Serial cardiac MRI was performed at 16, 33, and 62 days post-MI, including cine imaging, native and postcontrast T1 , T2 and dark-blood late gadolinium enhanced (DB-LGE) scar imaging.


Regions of interest were selected on the parametric maps to assess native T1 and T2 in the infarct and in remote tissue. Volume of enhanced tissue, nonenhanced tissue, and gray zone were assessed from DB-LGE imaging. Volumes, cardiac function, and strain were calculated from cine imaging.


Parameters estimated at more than two timepoints were compared with a one-way repeated measures analysis of variance. Parametric mapping data were analyzed using a generalized linear mixed model corrected for multiple observations. A result was considered statistically significant at P < 0.05.


All animals developed anteroseptal akinesia and hyperenhancement on DB-LGE with a central core of nonenhancing tissue. Mean hyperenhancement volume did not change during the observation period, while the central core contracted from 2.2 ± 1.8 ml at 16 days to 0.08 ± 0.19 ml at 62 days (P = 0.008). Native T1 of ischemic myocardium increased from 1173 ± 93 msec at 16 days to 1309 ± 97 msec at 62 days (P < 0.001). Mean radial and circumferential strain rate magnitude in remote myocardium increased with time from the infarct (P < 0.05).


In this swine model of MI, serial quantitative cardiac MR exams allow characterization of LV remodeling and scar formation.


2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

El-Rewaidy H, Nezafat M, Jang J, Nakamori S, Fahmy A, Nezafat R. Nonrigid Active Shape Model-Based Registration Framework for Motion Correction of Cardiac T1 Mapping. Magn Reson Med 2018;Abstract

ASM Reg T1

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.

Tan AY, Nearing BD, Rosenberg M, Nezafat R, Josephson ME, Verrier RL. 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 2017;28(11):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.
Nakamori S, Bui AH, Jang J, El-Rewaidy HA, Kato S, Ngo LH, Josephson ME, Manning WJ, Nezafat R. Increased myocardial native T1 relaxation time in patients with nonischemic dilated cardiomyopathy with complex ventricular arrhythmia. J Magn Reson Imaging 2017;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.
Messroghli DR, Moon JC, Ferreira VM, Grosse-Wortmann L, He T, Kellman P, Mascherbauer J, Nezafat R, Salerno M, Schelbert EB, Taylor AJ, Thompson R, Ugander M, van Heeswijk RB, Friedrich MG. 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 2017;19(1):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.
Nakamori S, Ismail H, Ngo LH, Manning WJ, Nezafat R. Left ventricular geometry predicts ventricular tachyarrhythmia in patients with left ventricular systolic dysfunction: a comprehensive cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2017;19(1):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.
Basha TA, Akçakaya M, Liew C, Tsao CW, Delling FN, Addae G, Ngo L, Manning WJ, Nezafat R. Clinical performance of high-resolution late gadolinium enhancement imaging with compressed sensing. J Magn Reson Imaging 2017;46(6):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.
Basha TA, Tang MC, Tsao C, Tschabrunn CM, Anter E, Manning WJ, Nezafat R. Improved dark blood late gadolinium enhancement (DB-LGE) imaging using an optimized joint inversion preparation and T2 magnetization preparation. Magn Reson Med 2017;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.
Bui AH, Roujol S, Foppa M, Kissinger KV, Goddu B, Hauser TH, Zimetbaum PJ, Ngo LH, Manning WJ, Nezafat R, Delling FN. Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia. Heart 2017;103(3):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.
Nakamori S, Alakbarli J, Bellm S, Motiwala SR, Addae G, Manning WJ, Nezafat R. Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction. J Magn Reson Imaging 2017;46(4):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.
Tschabrunn CM, Roujol S, Nezafat R, Faulkner-Jones B, Buxton AE, Josephson ME, Anter E. A swine model of infarct-related reentrant ventricular tachycardia: Electroanatomic, magnetic resonance, and histopathological characterization. Heart Rhythm 2016;13(1):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.
Akçakaya M, Weingärtner S, Basha TA, Roujol S, Bellm S, Nezafat R. Joint myocardial T1 and T2 mapping using a combination of saturation recovery and T2 -preparation. Magn Reson Med 2016;76(3):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.
Basha TA, Bellm S, Roujol S, Kato S, Nezafat R. Free-breathing slice-interleaved myocardial T2 mapping with slice-selective T2 magnetization preparation. Magn Reson Med 2016;76(2):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.
Kato S, Foppa M, Roujol S, Basha T, Berg S, Kissinger KV, Goddu B, Manning WJ, Nezafat R. 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 2016;203:848-54.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.
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