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.

El-Rewaidy H, Nakamori S, Addae G, Manning W, Nezafat R. Active shape models based motion correction for myocardial T1 Mapping. Proceedings of the 25th Annual Meeting of ISMRM Hawaii USA 2017;
Fahmy AS, Basha TA, Nezafat R. Analytically-derived parameter scouting for dark-blood Late Gadolinium Enhancement (DB-LGE) imaging. Proceedings of the 25th Annual Meeting of ISMRM  Hawaii USA 2017;
Nakamori S, Alakbarli J, Addae G, Jang J, Berg S, Kissinger KV, Goddu B, Manning WJ, Nezafat R. Changes in myocardial native T1 and T2 after physical exercise: A feasibility study. 20th Annual Scientific Sessions Society for Cardiovascular Magnetic Resonance Washington DC USA 2017;
Whitaker J, Tschabrunn C, Jang J, Leshem E, O’Neill M, Kissinger KV, Manning WJ, Anter E, Nezafat R. Characterization of left ventricular injury and remodelling using serial CMR scans in a swine model of myocardial infarction with ventricular arrhythmia. 20th Annual Scientific Sessions Society for Cardiovascular Magnetic Resonance Washington DC USA 2017;
Kang J, Jang J, Tarokh V, Nezafat R. Dictionary-based reconstruction for free-breathing myocardial T1 mapping. 25th Annual Meeting of ISMRM Hawaii USA 2017;
Rausch J, Menze BH, Chang R, Jang J, Applebaum E, Nezafat R. Fully automated left ventricle scar quantification with deep learning. Proceedings of the 25th Annual Meeting of ISMRM Hawaii USA 2017;
Whitaker J, Tschabrunn C, Anter E, Manning WJ, Nezafat R. Identification of right ventricular infarction using dark-blood late gadolinium enhanced LGE-CMR in a swine ischemia-reperfusion model. 20th Annual Scientific Sessions Society for Cardiovascular Magnetic Resonance Washington DC USA 2017;
Nakamori S, Ismail H, Ngo LH, Buxton AE, Manning WJ, Nezafat R. Impact of left ventricular geometry in predicting ventricular tachyarrhythmia in Patients with Left Ventricular Dysfunction: A Comprehensive Cardiovascular Magnetic Resonance Study . 20th Annual Scientific Sessions Society for Cardiovascular Magnetic Resonance Washington DC USA 2017;
Jang J, Nakamori S, Nezafat R. Improving precision of myocardial T1 mapping with 3-parameter model using tissue characteristic-based denoising. Proceedings of the 25th Annual Meeting of ISMRM Hawaii USA 2017;
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. 20th Annual Scientific Sessions Society for Cardiovascular Magnetic Resonance Washington DC USA 2017;
Jang J, Whitaker J, Tschabrunn CM, Leshem E, Contreras-Valdes FM, Anter E, Nezafat R. Optimal cut-off for unipolar and bipolar voltages to predict scar in LGE-MRI in swine model of ventricular tachycardia with Prior Myocardial Infarction. Heart Rhythm 2017 Chicago Illinois 2017;
Jang J, Contreras-Valdes FM, Tschabrunn CM, Leshem E, Whitaker J, Buxton AE, Nezafat R, Anter E. Substrate mapping of VT using decremental pacing: A novel strategy to identify localized regions susceptible for reentry. Heart Rhythm 2017 Chicago Illinois 2017;
Jang J, Addae G, Manning W, Nezafat R. Three-dimensional holographic visualization of high-resolution myocardial scar on HoloLens. Proceedings of the 25th Annual Meeting of ISMRM Hawaii USA 2017;
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, 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.
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.