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

Background: 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 ).
Methods and Results: 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).
Conclusions: 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.

Nakamori S, Fahmy AS, Jang J, El-Rewaidy H, Neisius U, Berg S, Goddu B, Pierce P, Manning WJ, Nezafat R. Changes in Myocardial T1 and T2 After Supine Exercise Stress in Healthy and Ischemic Myocardium: A Pilot Study. Abstract oral session presented at: Melvin Judkins Young Investigator Competition. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Nakamori S, Ngo LH, Tugal D, Manning WJ, Nezafat R. Incremental Value of Left Atrial Geometrical Remodeling in Predicting Late Atrial Fibrillation Recurrence After Pulmonary Vein Isolation: A Cardiovascular Magnetic Resonance Study . Abstract poster session presented at: Imaging Considerations in Arrhythmias and Electrophysiology. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Nakamori S, Neisius U, Nezafat M, Jang J, Ngo LH, Hwang H, Manning WJ, Nezafat R. Multiparametric Mapping Approach in the Detection of Subclinical Cardiac Involvement in Systemic Sarcoidosis. Abstract poster session presented at: Imaging of Nonischemic Cardiomyopathies. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Fahmy AS, El-Rewaidy H, Nakamori S, Nezafat R. Fully Automated Myocardial T1Quantification Using Fully Convolutional Neural Networks. Abstract poster session presented at: Advances in Cardiovascular Magnetic Resonance Imaging. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Fahmy AS, Rausch J, Neisius U, Chan RH, Maron MS, Appelbaum E, Menze B, Nezafat R. Fully Automated Quantification of Cardiac MR LV Mass and Scar in Hypertrophic Cardiomyopathy Using Deep Learning. Abstract oral session presented at: Charles Dotter Lecture. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Neisius U, Gona PN, Oyama-Manabe N, Chuang ML, O'Donnell CJ, Manning WJ, Tsao CW. CMR of Aortic Wall Area and Plaque and Association with Incident Adverse Cardiovascular Events: The Framingham Heart Study. Abstract poster session presented at: Imaging of Plaque and Atherosclerosis. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Neisius U, El-Rewaidy H, Nakamori S, Manning WJ, Nezafat R. Radiomics Analysis of Myocardial Native T1 Imaging Discriminates Between Hypertensive Heart Disease and Hypertrophic Cardiomyopathy. Abstract poster session presented at: Imaging of Nonischemic Cardiomyopathies. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
Neisius U, El-Rewaidy H, Nakamori S, Manning WJ, Nezafat R. Analysis of Myocardial Native T1 Imaging Discriminates Between Hypertensive Heart Disease and Hypertrophic Cardiomyopathy. In: Imaging of Nonischemic Cardiomyopathies. American Heart Association (AHA) Scientific Sessions. Chicago, IL, USA: 2018
Jang J, Hwang H, Tschabrunn CM, Whitaker J, Menze B, Anter E, Nezafat R. Structural Modeling in Cardiac MR Enables Detection of Three-Dimensional Heterogeneous Tissue Channel in Ventricular Arrhythmia: A Swine Study. Abstract poster session presented at: Advances in Cardiovascular Magnetic Resonance Imaging. American Heart Association (AHA) Scientific Sessions, Chicago, IL, USA. 2018;
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.
Fahmy AS, Rausch J, Neisius U, Chan RH, Maron MS, Appelbaum E, Menze B, Nezafat R. Automated Cardiac MR Scar Quantification in Hypertrophic Cardiomyopathy Using Deep Convolutional Neural Networks. JACC: Cardiovascular Imaging 2018; [PDF]
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.
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.
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.