Publications

2019
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

Objectives 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).

Background 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.

Methods 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.

Results 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).

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

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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

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

KEYWORDS:

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

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2018
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

PURPOSE:

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

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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

KEYWORDS:

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

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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

PURPOSE:

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

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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

KEYWORDS:

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

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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.

KEYWORDS:

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

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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.
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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

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

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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.
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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.
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