Daniel Ennis {he/him} is a Professor in the Department of Radiology. As an MRI scientist for nearly twenty years, he has worked to develop advanced translational cardiovascular MRI methods for quantitatively assessing structure, function, flow, and remodeling in both adult and pediatric populations. He began his research career as a Ph.D. student in the Department of Biomedical Engineering at Johns Hopkins University during which time he formed an active collaboration with investigators in the Laboratory of Cardiac Energetics at the National Heart, Lung, and Blood Institute (NIH/NHLBI). Thereafter, he joined the Departments of Radiological Sciences and Cardiothoracic Surgery at Stanford University as a postdoc and began to establish an independent research program with an NIH K99/R00 award focused on “Myocardial Structure, Function, and Remodeling in Mitral Regurgitation.” For ten years he led a group of clinicians and scientists at UCLA working to develop and evaluate advanced cardiovascular MRI exams as PI of several NIH funded studies. In 2018 he returned to the Department of Radiology at Stanford University as faculty in the Radiological Sciences Lab to bolster programs in cardiovascular MRI. He is also the Director of Radiology Research for the Veterans Administration Palo Alto Health Care System where he oversees a growing radiology research program.

Academic Appointments

Administrative Appointments

  • Director of Radiology Research, Veterans Affairs Palo Alto Health Care System (2018 - Present)

Honors & Awards

  • Young Investigator Award (Moore Award) {Mentor}, International Society for Magnetic Resonance in Medicine (2012)
  • Distinguished Reviewer Award, Magnetic Resonance in Medicine (2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019)
  • Outstanding Basic Science Faculty Teaching Award, Department of Radiology, University of California, Los Angeles (2014, 2016, 2017)
  • Fellow, Society for Cardiovascular Magnetic Resonance (2018)
  • Gold Star Reviewer, Journal of Cardiovascular Magnetic Resonance (2018)
  • Distinguished Investigator, Academy for Radiology and Biomedical Imaging Research (2020)
  • Fellow, International Society for Magnetic Resonance in Medicine (2020)

Boards, Advisory Committees, Professional Organizations

  • Chair (Founder), ISMRM Research Exchange Program (2016 - 2020)
  • Charter Member & Chair, NIH Imaging Technology Development (ITD) Study Section (2020 - Present)
  • Charter Member, NIH Imaging Technology Development (ITD) Study Section (2019 - 2020)
  • Member, NIH Biomedical Imaging Technology (BMIT) A & B Study Section (2017 - 2018)
  • Editorial Board, Journal of Cardiovascular Magnetic Resonance (2016 - Present)
  • Deputy Editor, Magnetic Resonance in Medicine (2016 - Present)

Professional Education

  • Post-Doc, Stanford University, Radiology and Cardiothoracic Surgery (2008)
  • Ph.D., Johns Hopkins University, Biomedical Engineering (2004)
  • B.S., University of California, San Diego, Bioengineering (1997)

2023-24 Courses

Stanford Advisees

All Publications

  • A deep learning approach for fast muscle water T2 mapping with subject specific fat T2 calibration from multi-spin-echo acquisitions. Scientific reports Barbieri, M., Hooijmans, M. T., Moulin, K., Cork, T. E., Ennis, D. B., Gold, G. E., Kogan, F., Mazzoli, V. 2024; 14 (1): 8253


    This work presents a deep learning approach for rapid and accurate muscle water T2 with subject-specific fat T2 calibration using multi-spin-echo acquisitions. This method addresses the computational limitations of conventional bi-component Extended Phase Graph fitting methods (nonlinear-least-squares and dictionary-based) by leveraging fully connected neural networks for fast processing with minimal computational resources. We validated the approach through in vivo experiments using two different MRI vendors. The results showed strong agreement of our deep learning approach with reference methods, summarized by Lin's concordance correlation coefficients ranging from 0.89 to 0.97. Further, the deep learning method achieved a significant computational time improvement, processing data 116 and 33 times faster than the nonlinear least squares and dictionary methods, respectively. In conclusion, the proposed approach demonstrated significant time and resource efficiency improvements over conventional methods while maintaining similar accuracy. This methodology makes the processing of water T2 data faster and easier for the user and will facilitate the utilization of the use of a quantitative water T2 map of muscle in clinical and research studies.

    View details for DOI 10.1038/s41598-024-58812-2

    View details for PubMedID 38589478

    View details for PubMedCentralID 6398566

  • A three-dimensional left atrial motion estimation from retrospective gated computed tomography: application in heart failure patients with atrial fibrillation FRONTIERS IN CARDIOVASCULAR MEDICINE Sillett, C., Razeghi, O., Lee, A. C., Solis Lemus, J., Roney, C., Mannina, C., de Vere, F., Ananthan, K., Ennis, D. B., Haberland, U., Xu, H., Young, A., Rinaldi, C. A., Rajani, R., Niederer, S. A. 2024; 11: 1359715


    A reduced left atrial (LA) strain correlates with the presence of atrial fibrillation (AF). Conventional atrial strain analysis uses two-dimensional (2D) imaging, which is, however, limited by atrial foreshortening and an underestimation of through-plane motion. Retrospective gated computed tomography (RGCT) produces high-fidelity three-dimensional (3D) images of the cardiac anatomy throughout the cardiac cycle that can be used for estimating 3D mechanics. Its feasibility for LA strain measurement, however, is understudied.The aim of this study is to develop and apply a novel workflow to estimate 3D LA motion and calculate the strain from RGCT imaging. The utility of global and regional strains to separate heart failure in patients with reduced ejection fraction (HFrEF) with and without AF is investigated.A cohort of 30 HFrEF patients with (n = 9) and without (n = 21) AF underwent RGCT prior to cardiac resynchronisation therapy. The temporal sparse free form deformation image registration method was optimised for LA feature tracking in RGCT images and used to estimate 3D LA endocardial motion. The area and fibre reservoir strains were calculated over the LA body. Universal atrial coordinates and a human atrial fibre atlas enabled the regional strain calculation and the fibre strain calculation along the local myofibre orientation, respectively.It was found that global reservoir strains were significantly reduced in the HFrEF + AF group patients compared with the HFrEF-only group patients (area strain: 11.2 ± 4.8% vs. 25.3 ± 12.6%, P = 0.001; fibre strain: 4.5 ± 2.0% vs. 15.2 ± 8.8%, P = 0.001), with HFrEF + AF patients having a greater regional reservoir strain dyssynchrony. All regional reservoir strains were reduced in the HFrEF + AF patient group, in whom the inferior wall strains exhibited the most significant differences. The global reservoir fibre strain and LA volume + posterior wall reservoir fibre strain exceeded LA volume alone and 2D global longitudinal strain (GLS) for AF classification (area-under-the-curve: global reservoir fibre strain: 0.94 ± 0.02, LA volume + posterior wall reservoir fibre strain: 0.95 ± 0.02, LA volume: 0.89 ± 0.03, 2D GLS: 0.90 ± 0.03).RGCT enables 3D LA motion estimation and strain calculation that outperforms 2D strain metrics and LA enlargement for AF classification. Differences in regional LA strain could reflect regional myocardial properties such as atrial fibrosis burden.

    View details for DOI 10.3389/fcvm.2024.1359715

    View details for Web of Science ID 001198345000001

    View details for PubMedID 38596691

    View details for PubMedCentralID PMC11002108

  • Pre-excitation gradients for eddy current nulled convex optimized diffusion encoding (Pre-ENCODE). Magnetic resonance in medicine Middione, M. J., Loecher, M., Cao, X., Setsompop, K., Ennis, D. B. 2024


    PURPOSE: To evaluate the use of pre-excitation gradients for eddy current-nulled convex optimized diffusion encoding (Pre-ENCODE) to mitigate eddy current-induced image distortions in diffusion-weighted MRI (DWI).METHODS: DWI sequences using monopolar (MONO), ENCODE, and Pre-ENCODE were evaluated in terms of the minimum achievable echo time (TE min $$ {}_{\mathrm{min}} $$ ) and eddy current-induced image distortions using simulations, phantom experiments, and in vivo DWI in volunteers ( N = 6 $$ N=6 $$ ).RESULTS: Pre-ENCODE provided a shorter TE min $$ {}_{\mathrm{min}} $$ than MONO (71.0 ± $$ \pm $$ 17.7ms vs. 77.6 ± $$ \pm $$ 22.9ms) and ENCODE (71.0 ± $$ \pm $$ 17.7ms vs. 86.2 ± $$ \pm $$ 14.2ms) in 100 % $$ \% $$ of the simulated cases for a commercial 3T MRI system with b-values ranging from 500 to 3000 s/mm 2 $$ {}^2 $$ and in-plane spatial resolutions ranging from 1.0 to 3.0mm 2 $$ {}^2 $$ . Image distortion was estimated by intravoxel signal variance between diffusion encoding directions near the phantom edges and was significantly lower with Pre-ENCODE than with MONO (10.1 % $$ \% $$ vs. 22.7 % $$ \% $$ , p = 6 - 5 $$ p={6}^{-5} $$ ) and comparable to ENCODE (10.1 % $$ \% $$ vs. 10.4 % $$ \% $$ , p = 0 . 12 $$ p=0.12 $$ ). In vivo measurements of apparent diffusion coefficients were similar in global brain pixels (0.37 [0.28,1.45] * 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s vs. 0.38 [0.28,1.45] * 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s, p = 0 . 25 $$ p=0.25 $$ ) and increased in edge brain pixels (0.80 [0.17,1.49] * 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s vs. 0.70 [0.18,1.48] * 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s, p = 0 . 02 $$ p=0.02 $$ ) for MONO compared to Pre-ENCODE.CONCLUSION: Pre-ENCODE mitigated eddy current-induced image distortions for diffusion imaging with a shorter TE min $$ {}_{\mathrm{min}} $$ than MONO and ENCODE.

    View details for DOI 10.1002/mrm.30068

    View details for PubMedID 38501914

  • Non-invasive Estimation of Pressure Drop Across Aortic Coarctations: Validation of 0D and 3D Computational Models with In Vivo Measurements. Annals of biomedical engineering Nair, P. J., Pfaller, M. R., Dual, S. A., McElhinney, D. B., Ennis, D. B., Marsden, A. L. 2024


    Blood pressure gradient ([Formula: see text]) across an aortic coarctation (CoA) is an important measurement to diagnose CoA severity and gauge treatment efficacy. Invasive cardiac catheterization is currently the gold-standard method for measuring blood pressure. The objective of this study was to evaluate the accuracy of [Formula: see text] estimates derived non-invasively using patient-specific 0D and 3D deformable wall simulations. Medical imaging and routine clinical measurements were used to create patient-specific models of patients with CoA (N = 17). 0D simulations were performed first and used to tune boundary conditions and initialize 3D simulations. [Formula: see text] across the CoA estimated using both 0D and 3D simulations were compared to invasive catheter-based pressure measurements for validation. The 0D simulations were extremely efficient ([Formula: see text] 15 s computation time) compared to 3D simulations ([Formula: see text] 30 h computation time on a cluster). However, the 0D [Formula: see text] estimates, unsurprisingly, had larger mean errors when compared to catheterization than 3D estimates (12.1 ± 9.9 mmHg vs 5.3 ± 5.4 mmHg). In particular, the 0D model performance degraded in cases where the CoA was adjacent to a bifurcation. The 0D model classified patients with severe CoA requiring intervention (defined as [Formula: see text] [Formula: see text] 20 mmHg) with 76% accuracy and 3D simulations improved this to 88%. Overall, a combined approach, using 0D models to efficiently tune and launch 3D models, offers the best combination of speed and accuracy for non-invasive classification of CoA severity.

    View details for DOI 10.1007/s10439-024-03457-5

    View details for PubMedID 38341399

  • SCMR Expert Consensus Statement for Cardiovascular Magnetic Resonance of Patients with a Cardiac Implantable Electronic Device. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Kim, D., Collins, J. D., White, J. A., Hanneman, K., Lee, D. C., Patel, A. R., Hu, P., Litt, H., Weinsaft, J. W., Davids, R., Mukai, K., Ng, M. Y., Luetkens, J. A., Roguin, A., Rochitte, C. E., Woodard, P. K., Manisty, C., Zareba, K. M., Mont, L., Bogun, F., Ennis, D. B., Nazarian, S., Webster, G., Stojanovska, J. 2024: 100995


    Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a consensus statement that integrates latest evidence concerning MR safety and CIED and CMR technologies. While experienced centers currently perform CMR in CIED patients, broad availability of CMR in this population is lacking, partially due to availability of resources for programming devices and appropriate monitoring, but also related to knowledge gaps regarding the risk-benefit ratio of CMR in this growing population. To address the knowledge gaps, this SCMR Expert Consensus Statement integrates consensus guidelines, primary data, and opinions from experts across disparate fields towards the shared goal of informing evidenced-based decision-making regarding the risk-benefit ratio of CMR for patients with CIEDs.

    View details for DOI 10.1016/j.jocmr.2024.100995

    View details for PubMedID 38219955

  • Hemodynamic effects of entry and exit tear size in aortic dissection evaluated with in vitro magnetic resonance imaging and fluid-structure interaction simulation. Scientific reports Zimmermann, J., Bäumler, K., Loecher, M., Cork, T. E., Marsden, A. L., Ennis, D. B., Fleischmann, D. 2023; 13 (1): 22557


    Understanding the complex interplay between morphologic and hemodynamic features in aortic dissection is critical for risk stratification and for the development of individualized therapy. This work evaluates the effects of entry and exit tear size on the hemodynamics in type B aortic dissection by comparing fluid-structure interaction (FSI) simulations with in vitro 4D-flow magnetic resonance imaging (MRI). A baseline patient-specific 3D-printed model and two variants with modified tear size (smaller entry tear, smaller exit tear) were embedded into a flow- and pressure-controlled setup to perform MRI as well as 12-point catheter-based pressure measurements. The same models defined the wall and fluid domains for FSI simulations, for which boundary conditions were matched with measured data. Results showed exceptionally well matched complex flow patterns between 4D-flow MRI and FSI simulations. Compared to the baseline model, false lumen flow volume decreased with either a smaller entry tear (- 17.8 and - 18.5%, for FSI simulation and 4D-flow MRI, respectively) or smaller exit tear (- 16.0 and - 17.3%). True to false lumen pressure difference (initially 11.0 and 7.9 mmHg, for FSI simulation and catheter-based pressure measurements, respectively) increased with a smaller entry tear (28.9 and 14.6 mmHg), and became negative with a smaller exit tear (- 20.6 and - 13.2 mmHg). This work establishes quantitative and qualitative effects of entry or exit tear size on hemodynamics in aortic dissection, with particularly notable impact observed on FL pressurization. FSI simulations demonstrate acceptable qualitative and quantitative agreement with flow imaging, supporting its deployment in clinical studies.

    View details for DOI 10.1038/s41598-023-49942-0

    View details for PubMedID 38110526

    View details for PubMedCentralID PMC10728172

  • SDF4CHD: Generative Modeling of Cardiac Anatomies with Congenital Heart Defects. ArXiv Kong, F., Stocker, S., Choi, P. S., Ma, M., Ennis, D. B., Marsden, A. 2023


    Congenital heart disease (CHD) encompasses a spectrum of cardiovascular structural abnormalities, often requiring customized treatment plans for individual patients. Computational modeling and analysis of these unique cardiac anatomies can improve diagnosis and treatment planning and may ultimately lead to improved outcomes. Deep learning (DL) methods have demonstrated the potential to enable efficient treatment planning by automating cardiac segmentation and mesh construction for patients with normal cardiac anatomies. However, CHDs are often rare, making it challenging to acquire sufficiently large patient cohorts for training such DL models. Generative modeling of cardiac anatomies has the potential to fill this gap via the generation of virtual cohorts; however, prior approaches were largely designed for normal anatomies and cannot readily capture the significant topological variations seen in CHD patients. Therefore, we propose a type- and shape-disentangled generative approach suitable to capture the wide spectrum of cardiac anatomies observed in different CHD types and synthesize differently shaped cardiac anatomies that preserve the unique topology for specific CHD types. Our DL approach represents generic whole heart anatomies with CHD type-specific abnormalities implicitly using signed distance fields (SDF) based on CHD type diagnosis, which conveniently captures divergent anatomical variations across different types and represents meaningful intermediate CHD states. To capture the shape-specific variations, we then learn invertible deformations to morph the learned CHD type-specific anatomies and reconstruct patient-specific shapes. Our approach has the potential to augment the image-segmentation pairs for rarer CHD types for cardiac segmentation and generate cohorts of CHD cardiac meshes for computational simulation.

    View details for PubMedID 37961745

    View details for PubMedCentralID PMC10635288

  • Coil sketching for computationally efficient MR iterative reconstruction. Magnetic resonance in medicine Oscanoa, J. A., Ong, F., Iyer, S. S., Li, Z., Sandino, C. M., Ozturkler, B., Ennis, D. B., Pilanci, M., Vasanawala, S. S. 2023


    Parallel imaging and compressed sensing reconstructions of large MRI datasets often have a prohibitive computational cost that bottlenecks clinical deployment, especially for three-dimensional (3D) non-Cartesian acquisitions. One common approach is to reduce the number of coil channels actively used during reconstruction as in coil compression. While effective for Cartesian imaging, coil compression inherently loses signal energy, producing shading artifacts that compromise image quality for 3D non-Cartesian imaging. We propose coil sketching, a general and versatile method for computationally-efficient iterative MR image reconstruction.We based our method on randomized sketching algorithms, a type of large-scale optimization algorithms well established in the fields of machine learning and big data analysis. We adapt the sketching theory to the MRI reconstruction problem via a structured sketching matrix that, similar to coil compression, considers high-energy virtual coils obtained from principal component analysis. But, unlike coil compression, it also considers random linear combinations of the remaining low-energy coils, effectively leveraging information from all coils.First, we performed ablation experiments to validate the sketching matrix design on both Cartesian and non-Cartesian datasets. The resulting design yielded both improved computatioanal efficiency and preserved signal-to-noise ratio (SNR) as measured by the inverse g-factor. Then, we verified the efficacy of our approach on high-dimensional non-Cartesian 3D cones datasets, where coil sketching yielded up to three-fold faster reconstructions with equivalent image quality.Coil sketching is a general and versatile reconstruction framework for computationally fast and memory-efficient reconstruction.

    View details for DOI 10.1002/mrm.29883

    View details for PubMedID 37848365

  • Abbreviated cardiac magnetic resonance imaging versus echocardiography for interval assessment of systolic function in Duchenne muscular dystrophy: patient satisfaction, clinical utility, and image quality. The international journal of cardiovascular imaging Chandrasekar, H., Kaufman, B. D., Beattie, M. J., Ennis, D. B., Syed, A. B., Zucker, E. J., Maskatia, S. A. 2023


    Poor acoustic windows make interval assessment of systolic function in patients with (Duchenne Muscular Dystrophy) DMD by echocardiography (echo) difficult. Cardiac magnetic resonance imaging (CMR) can be challenging in DMD patients due to study duration and patient discomfort. We developed an abbreviated CMR (aCMR) protocol and hypothesized that aCMR would compare favorably to echo in image quality and clinical utility without significant differences in exam duration, patient satisfaction, and functional measurements.DMD patients were recruited prospectively to undergo echo and aCMR. Modalities were compared with a global quality assessment score (GQAS), clinical utility score (CUS), and patient satisfaction score (PSS). Results were compared using Wilcoxon signed-rank tests, Spearman correlations, intraclass correlations, and Bland-Altman analyses.Nineteen DMD patients were included. PSS scores and exam duration were equivalent between modalities, while CUS and GQAS scores favored aCMR. ACMR scored markedly higher than echo in RV visualization and assessment of atrial size. Older age was negatively correlated with echo GQAS and CUS scores, as well as aCMR PSS scores. Higher BMI was positively correlated with aCMR GQAS scores. Nighttime PPV requirement and non-ambulatory status were correlated with worse echo CUS scores. Poor image quality precluding quantification existed in five (26%) echo and zero (0%) aCMR studies. There was moderate correlation between aCMR and echo for global circumferential strain and left ventricular four chamber global longitudinal strain.The aCMR protocol resulted in improved clinical relevance and quality scores relative to echo, without significant detriment to patient satisfaction or exam duration.

    View details for DOI 10.1007/s10554-023-02977-w

    View details for PubMedID 37831292

    View details for PubMedCentralID 8756173

  • Non-invasive estimation of pressure drop across aortic coarctations: validation of 0D and 3D computational models with in vivo measurements. medRxiv : the preprint server for health sciences Nair, P. J., Pfaller, M. R., Dual, S. A., McElhinney, D. B., Ennis, D. B., Marsden, A. L. 2023


    Blood pressure gradient (ΔP) across an aortic coarctation (CoA) is an important measurement to diagnose CoA severity and gauge treatment efficacy. Invasive cardiac catheterization is currently the gold-standard method for measuring blood pressure. The objective of this study was to evaluate the accuracy of ΔP estimates derived non-invasively using patient-specific 0D and 3D deformable wall simulations.Medical imaging and routine clinical measurements were used to create patient-specific models of patients with CoA (N=17). 0D simulations were performed first and used to tune boundary conditions and initialize 3D simulations. ΔP across the CoA estimated using both 0D and 3D simulations were compared to invasive catheter-based pressure measurements for validation.The 0D simulations were extremely efficient (~15 secs computation time) compared to 3D simulations (~30 hrs computation time on a cluster). However, the 0D ΔP estimates, unsurprisingly, had larger mean errors when compared to catheterization than 3D estimates (12.1 ± 9.9 mmHg vs 5.3 ± 5.4 mmHg). In particular, the 0D model performance degraded in cases where the CoA was adjacent to a bifurcation. The 0D model classified patients with severe CoA requiring intervention (defined as ΔP≥20 mmHg) with 76% accuracy and 3D simulations improved this to 88%.Overall, a combined approach, using 0D models to efficiently tune and launch 3D models, offers the best combination of speed and accuracy for non-invasive classification of CoA severity.

    View details for DOI 10.1101/2023.09.05.23295066

    View details for PubMedID 37732242

    View details for PubMedCentralID PMC10508787

  • Quinapril treatment curtails decline of global longitudinal strain and mechanical function in hypertensive rats. Journal of hypertension Wilson, A. J., Sands, G. B., Wang, V. Y., Pontre, B., Ennis, D. B., Young, A. A., LeGrice, I. J., Nash, M. P. 2023


    BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as an early imaging biomarker of cardiac mechanical dysfunction.OBJECTIVE: To assess the impact of angiotensin-converting enzyme (ACE) inhibitor treatment of hypertensive heart disease on LV GLS and mechanical function.METHODS: The spontaneously hypertensive rat (SHR) model of hypertensive heart disease (n = 38) was studied. A subset of SHRs received quinapril (TSHR, n = 16) from 3 months (mo). Wistar Kyoto rats (WKY, n = 13) were used as controls. Tagged cardiac MRI was performed using a 4.7 T Varian preclinical scanner.RESULTS: The SHRs had significantly lower LV ejection fraction (EF) than the WKYs at 3 mo (53.0 ± 1.7% vs. 69.6 ± 2.1%, P < 0.05), 14 mo (57.0 ± 2.5% vs. 74.4 ± 2.9%, P < 0.05) and 24 mo (50.1 ± 2.4% vs. 67.0 ± 2.0%, P < 0.01). At 24 mo, ACE inhibitor treatment was associated with significantly greater LV EF in TSHRs compared to untreated SHRs (64.2 ± 3.4% vs. 50.1 ± 2.4%, P < 0.01). Peak GLS magnitude was significantly lower in SHRs hearts compared with WKYs at 14 months (7.5% ± 0.4% vs. 9.9 ± 0.8%, P < 0.05). At 24 months, Peak GLS magnitude was significantly lower in SHRs compared with both WKYs (6.5 ± 0.4% vs. 9.7 ± 1.0%, P < 0.01) and TSHRs (6.5 ± 0.4% vs. 9.6 ± 0.6%, P < 0.05).CONCLUSIONS: ACE inhibitor treatment curtails the decline in global longitudinal strain in hypertensive rats, with the treatment group exhibiting significantly greater LV EF and GLS magnitude at 24 mo compared with untreated SHRs.

    View details for DOI 10.1097/HJH.0000000000003512

    View details for PubMedID 37466436

  • StrainNet: Improved Myocardial Strain Analysis of Cine MRI by Deep Learning from DENSE RADIOLOGY-CARDIOTHORACIC IMAGING Wang, Y., Sun, C., Ghadimi, S., Auger, D. C., Croisille, P., Viallon, M., Mangion, K., Berry, C., Haggerty, C. M., Jing, L., Fornwalt, B. K., Cao, J., Cheng, J., Scott, A. D., Ferreira, P. F., Oshinski, J. N., Ennis, D. B., Bilchick, K. C., Epstein, F. H. 2023; 5 (3)
  • StrainNet: Improved Myocardial Strain Analysis of Cine MRI by Deep Learning from DENSE. Radiology. Cardiothoracic imaging Wang, Y., Sun, C., Ghadimi, S., Auger, D. C., Croisille, P., Viallon, M., Mangion, K., Berry, C., Haggerty, C. M., Jing, L., Fornwalt, B. K., Cao, J. J., Cheng, J., Scott, A. D., Ferreira, P. F., Oshinski, J. N., Ennis, D. B., Bilchick, K. C., Epstein, F. H. 2023; 5 (3): e220196


    To develop a three-dimensional (two dimensions + time) convolutional neural network trained with displacement encoding with stimulated echoes (DENSE) data for displacement and strain analysis of cine MRI.In this retrospective multicenter study, a deep learning model (StrainNet) was developed to predict intramyocardial displacement from contour motion. Patients with various heart diseases and healthy controls underwent cardiac MRI examinations with DENSE between August 2008 and January 2022. Network training inputs were a time series of myocardial contours from DENSE magnitude images, and ground truth data were DENSE displacement measurements. Model performance was evaluated using pixelwise end-point error (EPE). For testing, StrainNet was applied to contour motion from cine MRI. Global and segmental circumferential strain (Ecc) derived from commercial feature tracking (FT), StrainNet, and DENSE (reference) were compared using intraclass correlation coefficients (ICCs), Pearson correlations, Bland-Altman analyses, paired t tests, and linear mixed-effects models.The study included 161 patients (110 men; mean age, 61 years ± 14 [SD]), 99 healthy adults (44 men; mean age, 35 years ± 15), and 45 healthy children and adolescents (21 males; mean age, 12 years ± 3). StrainNet showed good agreement with DENSE for intramyocardial displacement, with an average EPE of 0.75 mm ± 0.35. The ICCs between StrainNet and DENSE and FT and DENSE were 0.87 and 0.72, respectively, for global Ecc and 0.75 and 0.48, respectively, for segmental Ecc. Bland-Altman analysis showed that StrainNet had better agreement than FT with DENSE for global and segmental Ecc.StrainNet outperformed FT for global and segmental Ecc analysis of cine MRI.Keywords: Image Postprocessing, MR Imaging, Cardiac, Heart, Pediatrics, Technical Aspects, Technology Assessment, Strain, Deep Learning, DENSE Supplemental material is available for this article. © RSNA, 2023.

    View details for DOI 10.1148/ryct.220196

    View details for PubMedID 37404792

    View details for PubMedCentralID PMC10316292

  • In Vivo Cardiac Diffusion Imaging Without Motion-Compensation Leads to Unreasonably High Diffusivity. Journal of magnetic resonance imaging : JMRI Moulin, K., Stoeck, C. T., Axel, L., Broncano, J., Croisille, P., Dall'Armellina, E., Ennis, D. B., Ferreira, P. F., Gotschy, A., Miro, S., Schneider, J. E., Scott, A. D., Sosnovik, D. E., Teh, I., Tous, C., Tunnicliffe, E. M., Viallon, M., Nguyen, C. 2023

    View details for DOI 10.1002/jmri.28703

    View details for PubMedID 37000010

  • Hemodynamic Effects of Entry and Exit Tear Size in Aortic Dissection Evaluated with In Vitro Magnetic Resonance Imaging and Fluid-Structure Interaction Simulation. ArXiv Zimmermann, J., Bäumler, K., Loecher, M., Cork, T. E., Marsden, A. L., Ennis, D. B., Fleischmann, D. 2023


    Understanding the complex interplay between morphologic and hemodynamic features in aortic dissection is critical for risk stratification and for the development of individualized therapy. This work evaluates the effects of entry and exit tear size on the hemodynamics in type B aortic dissection by comparing fluid-structure interaction (FSI) simulations with in vitro 4D-flow magnetic resonance imaging (MRI). A baseline patient-specific 3D-printed model and two variants with modified tear size (smaller entry tear, smaller exit tear) were embedded into a flow- and pressure-controlled setup to perform MRI as well as 12-point catheter-based pressure measurements. The same models defined the wall and fluid domains for FSI simulations, for which boundary conditions were matched with measured data. Results showed exceptionally well matched complex flow patterns between 4D-flow MRI and FSI simulations. Compared to the baseline model, false lumen flow volume decreased with either a smaller entry tear (-17.8 and -18.5 %, for FSI simulation and 4D-flow MRI, respectively) or smaller exit tear (-16.0 and -17.3 %). True to false lumen pressure difference (initially 11.0 and 7.9 mmHg, for FSI simulation and catheter-based pressure measurements, respectively) increased with a smaller entry tear (28.9 and 14.6 mmHg), and became negative with a smaller exit tear (-20.6 and -13.2 mmHg). This work establishes quantitative and qualitative effects of entry or exit tear size on hemodynamics in aortic dissection, with particularly notable impact observed on FL pressurization. FSI simulations demonstrate acceptable qualitative and quantitative agreement with flow imaging, supporting its deployment in clinical studies.

    View details for DOI 10.1161/HCI.0000000000000075

    View details for PubMedID 36994169

    View details for PubMedCentralID PMC10055490

  • Validating MRI-Derived Myocardial Stiffness Estimates Using In Vitro Synthetic Heart Models. Annals of biomedical engineering Kolawole, F. O., Peirlinck, M., Cork, T. E., Levenston, M., Kuhl, E., Ennis, D. B. 2023


    Impaired cardiac filling in response to increased passive myocardial stiffness contributes to the pathophysiology of heart failure. By leveraging cardiac MRI data and ventricular pressure measurements, we can estimate in vivo passive myocardial stiffness using personalized inverse finite element models. While it is well-known that this approach is subject to uncertainties, only few studies quantify the accuracy of these stiffness estimates. This lack of validation is, at least in part, due to the absence of ground truth in vivo passive myocardial stiffness values. Here, using 3D printing, we created soft, homogenous, isotropic, hyperelastic heart phantoms of varying geometry and stiffness and simulate diastolic filling by incorporating the phantoms into an MRI-compatible left ventricular inflation system. We estimate phantom stiffness from MRI and pressure data using inverse finite element analyses based on a Neo-Hookean model. We demonstrate that our identified softest and stiffest values of 215.7 and 512.3kPa agree well with the ground truth of 226.2 and 526.4kPa. Overall, our estimated stiffnesses revealed a good agreement with the ground truth ([Formula: see text] error) across all models. Our results suggest that MRI-driven computational constitutive modeling can accurately estimate synthetic heart material stiffnesses in the range of 200-500kPa.

    View details for DOI 10.1007/s10439-023-03164-7

    View details for PubMedID 36914919

  • Deep Learning-Based Reconstruction for Cardiac MRI: A Review. Bioengineering (Basel, Switzerland) Oscanoa, J. A., Middione, M. J., Alkan, C., Yurt, M., Loecher, M., Vasanawala, S. S., Ennis, D. B. 2023; 10 (3)


    Cardiac magnetic resonance (CMR) is an essential clinical tool for the assessment of cardiovascular disease. Deep learning (DL) has recently revolutionized the field through image reconstruction techniques that allow unprecedented data undersampling rates. These fast acquisitions have the potential to considerably impact the diagnosis and treatment of cardiovascular disease. Herein, we provide a comprehensive review of DL-based reconstruction methods for CMR. We place special emphasis on state-of-the-art unrolled networks, which are heavily based on a conventional image reconstruction framework. We review the main DL-based methods and connect them to the relevant conventional reconstruction theory. Next, we review several methods developed to tackle specific challenges that arise from the characteristics of CMR data. Then, we focus on DL-based methods developed for specific CMR applications, including flow imaging, late gadolinium enhancement, and quantitative tissue characterization. Finally, we discuss the pitfalls and future outlook of DL-based reconstructions in CMR, focusing on the robustness, interpretability, clinical deployment, and potential for new methods.

    View details for DOI 10.3390/bioengineering10030334

    View details for PubMedID 36978725

  • Seeing the Unseen in Cardiac Remodeling: Cardiac Diffusion Tensor Imaging as a Structural Biomarker in STEMI. JACC. Cardiovascular imaging Ennis, D. B., Salerno, M. 2023; 16 (2): 172-174

    View details for DOI 10.1016/j.jcmg.2022.12.011

    View details for PubMedID 36754476

  • Myocardial Segmentation of Tagged Magnetic Resonance Images with Transfer Learning Using Generative Cine-To-Tagged Dataset Transformation. Bioengineering (Basel, Switzerland) Dhaene, A. P., Loecher, M., Wilson, A. J., Ennis, D. B. 2023; 10 (2)


    The use of deep learning (DL) segmentation in cardiac MRI has the potential to streamline the radiology workflow, particularly for the measurement of myocardial strain. Recent efforts in DL motion tracking models have drastically reduced the time needed to measure the heart's displacement field and the subsequent myocardial strain estimation. However, the selection of initial myocardial reference points is not automated and still requires manual input from domain experts. Segmentation of the myocardium is a key step for initializing reference points. While high-performing myocardial segmentation models exist for cine images, this is not the case for tagged images. In this work, we developed and compared two novel DL models (nnU-net and Segmentation ResNet VAE) for the segmentation of myocardium from tagged CMR images. We implemented two methods to transform cardiac cine images into tagged images, allowing us to leverage large public annotated cine datasets. The cine-to-tagged methods included (i) a novel physics-driven transformation model, and (ii) a generative adversarial network (GAN) style transfer model. We show that pretrained models perform better (+2.8 Dice coefficient percentage points) and converge faster (6×) than models trained from scratch. The best-performing method relies on a pretraining with an unpaired, unlabeled, and structure-preserving generative model trained to transform cine images into their tagged-appearing equivalents. Our state-of-the-art myocardium segmentation network reached a Dice coefficient of 0.828 and 95th percentile Hausdorff distance of 4.745 mm on a held-out test set. This performance is comparable to existing state-of-the-art segmentation networks for cine images.

    View details for DOI 10.3390/bioengineering10020166

    View details for PubMedID 36829660

  • Hemodynamic Effects of Entry Versus Exit Tear Size and Tissue Stiffness in Simulations of Aortic Dissection Baumler, K., Zimmermann, J., Ennis, D. B., Marsden, A. L., Fleischmann, D., Tavares, J. M., Bourauel, C., Geris, L., Slote, J. V. SPRINGER INTERNATIONAL PUBLISHING AG. 2023: 143-152
  • Multishot Diffusion-Weighted MRI of the Breasts in the Supine vs. Prone Position. Journal of magnetic resonance imaging : JMRI Moran, C. J., Middione, M. J., Mazzoli, V., McKay-Nault, J. A., Guidon, A., Waheed, U., Rosen, E. L., Poplack, S. P., Rosenberg, J., Ennis, D. B., Hargreaves, B. A., Daniel, B. L. 2022


    BACKGROUND: Diffusion-weighted imaging (DWI) may allow for breast cancer screening MRI without a contrast injection. Multishot methods improve prone DWI of the breasts but face different challenges in the supine position.PURPOSE: To establish a multishot DWI (msDWI) protocol for supine breast MRI and to evaluate the performance of supine vs. prone msDWI.STUDY TYPE: Prospective.POPULATION: Protocol optimization: 10 healthy women (ages 22-56), supine vs. prone: 24 healthy women (ages 22-62) and five women (ages 29-61) with breast tumors.FIELD STRENGTH/SEQUENCE: 3-T, protocol optimization msDWI: free-breathing (FB) 2-shots, FB 4-shots, respiratory-triggered (RT) 2-shots, RT 4-shots, supine vs. prone: RT 4-shot msDWI, T2-weighted fast-spin echo.ASSESSMENT: Protocol optimization and supine vs. prone: three observers performed an image quality assessment of sharpness, aliasing, distortion (vs. T2), perceived SNR, and overall image quality (scale of 1-5). Apparent diffusion coefficients (ADCs) in fibroglandular tissue (FGT) and breast tumors were measured.STATISTICAL TESTS: Effect of study variables on dichotomized ratings (4/5 vs. 1/2/3) and FGT ADCs were assessed with mixed-effects logistic regression. Interobserver agreement utilized Gwet's agreement coefficient (AC). Lesion ADCs were assessed by Bland-Altman analysis and concordance correlation (rhoc ). P value <0.05 was considered statistically significant.RESULTS: Protocol optimization: 4-shots significantly improved sharpness and distortion; RT significantly improved sharpness, aliasing, perceived SNR, and overall image quality. FGT ADCs were not significantly different between shots (P=0.812), FB vs. RT (P=0.591), or side (P=0.574). Supine vs. prone: supine images were rated significantly higher for sharpness, aliasing, and overall image quality. FGT ADCs were significantly higher supine; lesion ADCs were highly correlated (rhoc =0.92).DATA CONCLUSION: Based on image quality, supine msDWI outperformed prone msDWI. Lesion ADCs were highly correlated between the two positions, while FGT ADCs were higher in the supine position.EVIDENCE LEVEL: 2.TECHNICAL EFFICACY: Stage 1.

    View details for DOI 10.1002/jmri.28582

    View details for PubMedID 36583628

  • 4D flow cardiovascular magnetic resonance recovery profiles following pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Dong, M. L., Azarine, A., Haddad, F., Amsallem, M., Kim, Y., Yang, W., Fadel, E., Aubrege, L., Loecher, M., Ennis, D., Pavec, J. L., Vignon-Clementel, I., Feinstein, J. A., Mercier, O., Marsden, A. L. 2022; 24 (1): 59


    BACKGROUND: Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness.METHODS: Twenty patients with CTEPH underwent pre-PEA and >6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity.RESULTS: Mean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P<0.002). 4D flow-derived PA volumes decreased (P<0.001) and stiffness, velocity, and vorticity increased (P<0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r=0.68, P=0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P<0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r=0.75, P=0.003) and minimum MPA HFI (r=-0.72, P=0.005).CONCLUSION: We developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.

    View details for DOI 10.1186/s12968-022-00893-x

    View details for PubMedID 36372884

  • Electrohydraulic Vascular Compression Device (e-VaC) with Integrated Sensing and Controls ADVANCED MATERIALS TECHNOLOGIES Pirozzi, I., Kight, A., Liang, X., Han, A., Ennis, D. B., Hiesinger, W., Dual, S. A., Cutkosky, M. R. 2022
  • Accelerated two-dimensional phase-contrast for cardiovascular MRI using deep learning-based reconstruction with complex difference estimation. Magnetic resonance in medicine Oscanoa, J. A., Middione, M. J., Syed, A. B., Sandino, C. M., Vasanawala, S. S., Ennis, D. B. 2022


    PURPOSE: To develop and validate a deep learning-based reconstruction framework for highly accelerated two-dimensional (2D) phase contrast (PC-MRI) data with accurate and precise quantitative measurements.METHODS: We propose a modified DL-ESPIRiT reconstruction framework for 2D PC-MRI, comprised of an unrolled neural network architecture with a Complex Difference estimation (CD-DL). CD-DL was trained on 155 fully sampled 2D PC-MRI pediatric clinical datasets. The fully sampled data ( n = 29 $$ n=29 $$ ) was retrospectively undersampled (6-11 * $$ \times $$ ) and reconstructed using CD-DL and a parallel imaging and compressed sensing method (PICS). Measurements of peak velocity and total flow were compared to determine the highest acceleration rate that provided accuracy and precision within ± 5 % $$ \pm 5\% $$ . Feasibility of CD-DL was demonstrated on prospectively undersampled datasets acquired in pediatric clinical patients ( n = 5 $$ n=5 $$ ) and compared to traditional parallel imaging (PI) and PICS.RESULTS: The retrospective evaluation showed that 9 * $$ \times $$ accelerated 2D PC-MRI images reconstructed with CD-DL provided accuracy and precision (bias, [95 % $$ \% $$ confidence intervals]) within ± 5 % $$ \pm 5\% $$ . CD-DL showed higher accuracy and precision compared to PICS for measurements of peak velocity (2.8 % $$ \% $$ [ - 2 . 9 $$ -2.9 $$ , 4.5] vs. 3.9 % $$ \% $$ [ - 11 . 0 $$ -11.0 $$ , 4.9]) and total flow (1.8 % $$ \% $$ [ - 3 . 9 $$ -3.9 $$ , 3.4] vs. 2.9 % $$ \% $$ [ - 7 . 1 $$ -7.1 $$ , 6.9]). The prospective feasibility study showed that CD-DL provided higher accuracy and precision than PICS for measurements of peak velocity and total flow.CONCLUSION: In a retrospective evaluation, CD-DL produced quantitative measurements of 2D PC-MRI peak velocity and total flow with ≤ 5 % $$ \le 5\% $$ error in both accuracy and precision for up to 9 * $$ \times $$ acceleration. Clinical feasibility was demonstrated using a prospective clinical deployment of our 8 * $$ \times $$ undersampled acquisition and CD-DL reconstruction in a cohort of pediatric patients.

    View details for DOI 10.1002/mrm.29441

    View details for PubMedID 36093915

  • Validation of the Reduced Unified Continuum Formulation Against In Vitro 4D-Flow MRI. Annals of biomedical engineering Lan, I. S., Liu, J., Yang, W., Zimmermann, J., Ennis, D. B., Marsden, A. L. 2022


    We previously introduced and verified the reduced unified continuum formulation for vascular fluid-structure interaction (FSI) against Womersley's deformable wall theory. Our present work seeks to investigate its performance in a patient-specific aortic setting in which assumptions of idealized geometries and velocity profiles are invalid. Specifically, we leveraged 2D magnetic resonance imaging (MRI) and 4D-flow MRI to extract high-resolution anatomical and hemodynamic information from an in vitro flow circuit embedding a compliant 3D-printed aortic phantom. To accurately reflect experimental conditions, we numerically implemented viscoelastic external tissue support, vascular tissue prestressing, and skew boundary conditions enabling in-plane vascular motion at each inlet and outlet. Validation of our formulation is achieved through close quantitative agreement in pressures, lumen area changes, pulse wave velocity, and early systolic velocities, as well as qualitative agreement in late systolic flow structures. Our validated suite of FSI techniques offers a computationally efficient approach for numerical simulation of vascular hemodynamics. This study is among the first to validate a cardiovascular FSI formulation against an in vitro flow circuit involving a compliant vascular phantom of complex patient-specific anatomy.

    View details for DOI 10.1007/s10439-022-03038-4

    View details for PubMedID 35963921

  • Framework for patient-specific simulation of hemodynamics in heart failure with counterpulsation support. Frontiers in cardiovascular medicine Arduini, M., Pham, J., Marsden, A. L., Chen, I. Y., Ennis, D. B., Dual, S. A. 2022; 9: 895291


    Despite being responsible for half of heart failure-related hospitalizations, heart failure with preserved ejection fraction (HFpEF) has limited evidence-based treatment options. Currently, a substantial clinical issue is that the disease etiology is very heterogenous with no patient-specific treatment options. Modeling can provide a framework for evaluating alternative treatment strategies. Counterpulsation strategies have the capacity to improve left ventricular diastolic filling by reducing systolic blood pressure and augmenting the diastolic pressure that drives coronary perfusion. Here, we propose a framework for testing the effectiveness of a soft robotic extra-aortic counterpulsation strategy using a patient-specific closed-loop hemodynamic lumped parameter model of a patient with HFpEF. The soft robotic device prototype was characterized experimentally in a physiologically pressurized (50-150 mmHg) soft silicone vessel and modeled as a combination of a pressure source and a capacitance. The patient-specific model was created using open-source software and validated against hemodynamics obtained by imaging of a patient (male, 87 years, HR = 60 bpm) with HFpEF. The impact of actuation timing on the flows and pressures as well as systolic function was analyzed. Good agreement between the patient-specific model and patient data was achieved with relative errors below 5% in all categories except for the diastolic aortic root pressure and the end systolic volume. The most effective reduction in systolic pressure compared to baseline (147 vs. 141 mmHg) was achieved when actuating 350 ms before systole. In this case, flow splits were preserved, and cardiac output was increased (5.17 vs. 5.34 L/min), resulting in increased blood flow to the coronaries (0.15 vs. 0.16 L/min). Both arterial elastance (0.77 vs. 0.74 mmHg/mL) and stroke work (11.8 vs. 10.6 kJ) were decreased compared to baseline, however left atrial pressure increased (11.2 vs. 11.5 mmHg). A higher actuation pressure is associated with higher systolic pressure reduction and slightly higher coronary flow. The soft robotic device prototype achieves reduced systolic pressure, reduced stroke work, slightly increased coronary perfusion, but increased left atrial pressures in HFpEF patients. In future work, the framework could include additional physiological mechanisms, a larger patient cohort with HFpEF, and testing against clinically used devices.

    View details for DOI 10.3389/fcvm.2022.895291

    View details for PubMedID 35979018

    View details for PubMedCentralID PMC9376255

  • Myocardial Mesostructure and Mesofunction. American journal of physiology. Heart and circulatory physiology Wilson, A. J., Sands, G. B., LeGrice, I. J., Young, A. A., Ennis, D. B. 2022


    The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten approximately 15% and increase in diameter approximately 8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, while magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (tens to hundreds of microns) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (cDTI) and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cDTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.

    View details for DOI 10.1152/ajpheart.00059.2022

    View details for PubMedID 35657613

  • Reproducibility of global and segmental myocardial strain using cine DENSE at 3T: a multicenter cardiovascular magnetic resonance study in healthy subjects and patients withheart disease. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Auger, D. A., Ghadimi, S., Cai, X., Reagan, C. E., Sun, C., Abdi, M., Cao, J. J., Cheng, J. Y., Ngai, N., Scott, A. D., Ferreira, P. F., Oshinski, J. N., Emamifar, N., Ennis, D. B., Loecher, M., Liu, Z., Croisille, P., Viallon, M., Bilchick, K. C., Epstein, F. H. 2022; 24 (1): 23


    BACKGROUND: While multiple cardiovascular magnetic resonance (CMR) methods provide excellent reproducibility of global circumferential and global longitudinal strain, achieving highly reproducible segmental strain is more challenging. Previous single-center studies have demonstrated excellent reproducibility of displacement encoding with stimulated echoes (DENSE) segmental circumferential strain. The present study evaluated the reproducibility of DENSE for measurement of whole-slice or global circumferential (Ecc), longitudinal (Ell) and radial (Err) strain, torsion, and segmental Ecc at multiple centers.METHODS: Six centers participated and a total of 81 subjects were studied, including 60 healthy subjects and 21 patients with various types of heart disease. CMR utilized 3T scanners, and cine DENSE images were acquired in three short-axis planes and in the four-chamber long-axis view. During one imaging session, each subject underwent two separate DENSE scans to assess inter-scan reproducibility. Each subject was taken out of the scanner and repositioned between the scans. Intra-user, inter-user-same-site, inter-user-different-site, and inter-user-Human-Deep-Learning (DL) comparisons assessed the reproducibility of different users analyzing the same data. Inter-scan comparisons assessed the reproducibility of DENSE from scan to scan. The reproducibility of whole-slice or global Ecc, Ell and Err, torsion, and segmental Ecc were quantified using Bland-Altman analysis, the coefficient of variation (CV), and the intraclass correlation coefficient (ICC). CV was considered excellent for CV≤10%, good for 10%40. ICC values were considered excellent for ICC>0.74, good for ICC 0.6

    View details for DOI 10.1186/s12968-022-00851-7

    View details for PubMedID 35369885

  • In Vivo Super-Resolution Cardiac Diffusion Tensor MRI: A Feasibility Study. Diagnostics (Basel, Switzerland) Le Bars, A., Moulin, K., Ennis, D. B., Felblinger, J., Chen, B., Odille, F. 2022; 12 (4)


    A super-resolution (SR) technique is proposed for imaging myocardial fiber architecture with cardiac magnetic resonance. Images were acquired with a motion-compensated cardiac diffusion tensor imaging (cDTI) sequence. The heart left ventricle was covered with three stacks of thick slices, in short axis, horizontal and vertical long axes orientations, respectively. The three low-resolution stacks (2 * 2 * 8 mm3) were combined into an isotropic volume (2 * 2 * 2 mm3) by a super-resolution reconstruction. For in vivo measurements, each slice was acquired during a breath-hold period. Bulk motion was corrected by optimizing a similarity metric between intensity profiles from all intersecting slices in the dataset. The benefit of the proposed approach was evaluated using a numerical heart phantom, a physical helicoidal phantom with artificial fibers, and six healthy subjects. The SR technique showed improved results compared to the native scans, in terms of image quality and cDTI metrics. In particular, the myocardial helix angle (HA) was more accurately estimated in the physical phantom (HA = 41.5° ± 1.1°, with the ground truth being 42.0°). In vivo, it resulted in a sharper rate of change of HA across the myocardial wall (-0.993°/% ± 0.007°/% against -0.873°/% ± 0.010°/%).

    View details for DOI 10.3390/diagnostics12040877

    View details for PubMedID 35453925

  • Validation of cardiac diffusion tensor imaging sequences: A multi-centre test-retest phantom study. NMR in biomedicine Teh, I., Romero, W., Boyle, J., Coll-Font, J., Dall'Armellina, E., Ennis, D. B., Ferreira, P. F., Kalra, P., Kolipaka, A., Kozerke, S., Lohr, D., Mongeon, F., Moulin, K., Nguyen, C., Nielles-Vallespin, S., Raterman, B., Schreiber, L. M., Scott, A. D., Sosnovik, D. E., Stoeck, C. T., Tous, C., Tunnicliffe, E. M., Weng, A. M., Croisille, P., Viallon, M., Schneider, J. E. 1800: e4685


    INTRODUCTION: Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI between ten centres internationally.METHODS: Phantoms comprising 0-20% polyvinylpyrrolidone (PVP) were scanned with DTI using a product pulsed gradient spin echo (PGSE; N=10 sites) sequence, and a custom motion-compensated spin echo (SE; N=5) or stimulated echo (STEAM; N=5) sequence suitable for cardiac DTI in vivo. A second identical scan was performed 1-9 days post, and the data analysed centrally.RESULTS: The average mean diffusivities (MD) in 0% PVP were (1.124, 1.130, 1.113) * 10-3 mm2 /s for PGSE, SE and STEAM respectively, and accurate to within 1.5% of reference data from literature. The coefficients of variation in MD across sites were 2.6%, 3.1%, 2.1% for PGSE, SE and STEAM, and were similar to previous studies using only PGSE. Reproducibility in MD was excellent, with mean differences in PGSE, SE and STEAM of (0.3 ± 2.3, 0.24 ± 0.95, 0.52 ± 0.58) * 10-5 mm2 /s (mean ± 1.96SD).CONCLUSION: We show that custom sequences for cardiac DTI provide accurate, precise, repeatable and reproducible measurements. Further work in anisotropic and/or deforming phantoms is warranted.

    View details for DOI 10.1002/nbm.4685

    View details for PubMedID 34967060

  • Diffusion biomarkers in chronic myocardial infarction. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Rahman, T., Moulin, K., Ennis, D. B., Perotti, L. E. 2021; 12738: 137-147


    Cardiac diffusion tensor magnetic resonance imaging (cDTI) allows estimating the aggregate cardiomyocyte architecture in healthy subjects and its remodeling as a result of cardiac disease. In this study, cDTI was used to quantify microstructural changes occurring in swine (N=7) six to ten weeks after myocardial infarction. Each heart was extracted and imaged ex vivo with 1mm isotropic spatial resolution. Microstructural changes were quantified in the border zone and infarct region by comparing diffusion tensor invariants - fractional anisotropy (FA), mode, and mean diffusivity (MD) - radial diffusivity, and diffusion tensor eigenvalues with the corresponding values in the remote myocardium. MD and radial diffusivity increased in the infarct and border regions with respect to the remote myocardium (p<0.01). In contrast, FA and mode decreased in the infarct and border regions (p<0.01). Diffusion tensor eigenvalues also increased in the infarct and border regions, with a larger increase in the secondary and tertiary eigenvalues.

    View details for DOI 10.1007/978-3-030-78710-3_14

    View details for PubMedID 34585174

  • Reproducibility of Left Ventricular CINE DENSE Strain in Pediatric Subjects with Duchenne Muscular Dystrophy. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Liu, Z. Q., Maforo, N. G., Renella, P., Halnon, N., Wu, H. H., Ennis, D. B. 2021; 12738: 232-241


    Cardiomyopathy is the leading cause of mortality in boys with Duchenne muscular dystrophy (DMD). Left ventricular (LV) peak mid-wall circumferential strain (Ecc) is a sensitive early biomarker for evaluating both the subtle and variable onset and the progression of cardiomyopathy in pediatric subjects with DMD. Cine Displacement Encoding with Stimulated Echoes (DENSE) has proven sensitive to changes in Ecc, but its reproducibility has not been reported in a pediatric cohort or a DMD cohort. The objective was to quantify the intra-observer repeatability, and intra-exam and inter-observer reproducibility of global and regional Ecc derived from cine DENSE in DMD patients (N = 10) and age-and sex-matched controls (N = 10). Global and regional Ecc measures were considered reproducible in the intra-exam, intra-observer, and inter-observer comparisons. Intra-observer repeatability was highest, followed by intra-exam reproducibility and then inter-observer reproducibility. The smallest detectable change in Ecc was 0.01 for the intra-observer comparison, which is below the previously reported yearly decrease of 0.013 ± 0.015 in Ecc in DMD patients.

    View details for DOI 10.1007/978-3-030-78710-3_23

    View details for PubMedID 36939420

    View details for PubMedCentralID PMC10022706

  • Optimisation of Left Atrial Feature Tracking Using Retrospective Gated Computed Tomography Images. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Sillett, C., Razeghi, O., Strocchi, M., Roney, C. H., O'Brien, H., Ennis, D. B., Haberland, U., Rajani, R., Rinaldi, C. A., Niederer, S. A. 2021; 12738: 71-83


    Retrospective gated cardiac computed tomography (CCT) images can provide high contrast and resolution images of the heart throughout the cardiac cycle. Feature tracking in retrospective CCT images using the temporal sparse free-form deformations (TSFFDs) registration method has previously been optimised for the left ventricle (LV). However, there is limited work on optimising nonrigid registration methods for feature tracking in the left atria (LA). This paper systematically optimises the sparsity weight (SW) and bending energy (BE) as two hyperparameters of the TSFFD method to track the LA endocardium from end-diastole (ED) to end-systole (ES) using 10-frame retrospective gated CCT images. The effect of two different control point (CP) grid resolutions was also investigated. TSFFD optimisation was achieved using the average surface distance (ASD), directed Hausdorff distance (DHD) and Dice score between the registered and ground truth surface meshes and segmentations at ES. For baseline comparison, the configuration optimised for LV feature tracking gave errors across the cohort of 0.826 ± 0.172mm ASD, 5.882 ± 1.524mm DHD, and 0.912 ± 0.033 Dice score. Optimising the SW and BE hyperparameters improved the TSFFD performance in tracking LA features, with case specific optimisations giving errors across the cohort of 0.750 ± 0.144mm ASD, 5.096 ± 1.246mm DHD, and 0.919 ± 0.029 Dice score. Increasing the CP resolution and optimising the SW and BE further improved tracking performance, with case specific optimisation errors of 0.372 ± 0.051mm ASD, 2.739 ± 0.843mm DHD and 0.949 ± 0.018 Dice score across the cohort. We therefore show LA feature tracking using TSFFDs is improved through a chamber-specific optimised configuration.

    View details for DOI 10.1007/978-3-030-78710-3_8

    View details for PubMedID 35727914

    View details for PubMedCentralID PMC9170531

  • Arbitrary Point Tracking with Machine Learning to Measure Cardiac Strains in Tagged MRI. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Loecher, M., Hannum, A. J., Perotti, L. E., Ennis, D. B. 2021; 12738: 213-222


    Cardiac tagged MR images allow for deformation fields to be measured in the heart by tracking the motion of tag lines throughout the cardiac cycle. Machine learning (ML) algorithms enable accurate and robust tracking of tag lines. Herein, the use of a massive synthetic physics-driven training dataset with known ground truth was used to train an ML network to enable tracking any number of points at arbitrary positions rather than anchored to the tag lines themselves. The tag tracking and strain calculation methods were investigated in a computational deforming cardiac phantom with known (ground truth) strain values. This enabled both tag tracking and strain accuracy to be characterized for a range of image acquisition and tag tracking parameters. The methods were also tested on in vivo volunteer data. Median tracking error was <0.26mm in the computational phantom, and strain measurements were improved in vivo when using the arbitrary point tracking for a standard clinical protocol.

    View details for DOI 10.1007/978-3-030-78710-3_21

    View details for PubMedID 34590079

  • Right Ventricular Function and T1-Mapping in Boys With Duchenne Muscular Dystrophy. Journal of magnetic resonance imaging : JMRI Dual, S. A., Maforo, N. G., McElhinney, D. B., Prosper, A., Wu, H. H., Maskatia, S., Renella, P., Halnon, N., Ennis, D. B. 2021


    BACKGROUND: Clinical management of boys with Duchenne muscular dystrophy (DMD) relies on in-depth understanding of cardiac involvement, but right ventricular (RV) structural and functional remodeling remains understudied.PURPOSE: To evaluate several analysis methods and identify the most reliable one to measure RV pre- and postcontrast T1 (RV-T1) and to characterize myocardial remodeling in the RV of boys with DMD.STUDY TYPE: Prospective.POPULATION: Boys with DMD (N=27) and age-/sex-matched healthy controls (N=17) from two sites.FIELD STRENGTH/SEQUENCE: 3.0T using balanced steady state free precession, motion-corrected phase sensitive inversion recovery and modified Look-Locker inversion recovery sequences.ASSESSMENT: Biventricular mass (Mi), end-diastolic volume (EDVi) and ejection fraction (EF) assessment, tricuspid annular excursion (TAE), late gadolinium enhancement (LGE), pre- and postcontrast myocardial T1 maps. The RV-T1 reliability was assessed by three observers in four different RV regions of interest (ROI) using intraclass correlation (ICC).STATISTICAL TESTS: The Wilcoxon rank sum test was used to compare RV-T1 differences between DMD boys with negative LGE(-) or positive LGE(+) and healthy controls. Additionally, correlation of precontrast RV-T1 with functional measures was performed. A P-value <0.05 was considered statistically significant.RESULTS: A 1-pixel thick RV circumferential ROI proved most reliable (ICC>0.91) for assessing RV-T1. Precontrast RV-T1 was significantly higher in boys with DMD compared to controls. Both LGE(-) and LGE(+) boys had significantly elevated precontrast RV-T1 compared to controls (1543 [1489-1597] msec and 1550 [1402-1699] msec vs. 1436 [1399-1473] msec, respectively). Compared to healthy controls, boys with DMD had preserved RVEF (51.8 [9.9]% vs. 54.2 [7.2]%, P=0.31) and significantly reduced RVMi (29.8 [9.7]g vs. 48.0 [15.7]g), RVEDVi (69.8 [29.7]mL/m2 vs. 89.1 [21.9]mL/m2 ), and TAE (22.0 [3.2]cm vs. 26.0 [4.7]cm). Significant correlations were found between precontrast RV-T1 and RVEF (beta=-0.48%/msec) and between LV-T1 and LVEF (beta=-0.51%/msec).DATA CONCLUSION: Precontrast RV-T1 is elevated in boys with DMD compared to healthy controls and is negatively correlated with RVEF.LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

    View details for DOI 10.1002/jmri.27729

    View details for PubMedID 34037289

  • Fully-automated global and segmental strain analysis of DENSE cardiovascular magnetic resonance using deep learning for segmentation and phase unwrapping. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Ghadimi, S., Auger, D. A., Feng, X., Sun, C., Meyer, C. H., Bilchick, K. C., Cao, J. J., Scott, A. D., Oshinski, J. N., Ennis, D. B., Epstein, F. H. 2021; 23 (1): 20


    BACKGROUND: Cardiovascular magnetic resonance (CMR) cine displacement encoding with stimulated echoes (DENSE) measures heart motion by encoding myocardial displacement into the signal phase, facilitating high accuracy and reproducibility of global and segmental myocardial strain and providing benefits in clinical performance. While conventional methods for strain analysis of DENSE images are faster than those for myocardial tagging, they still require manual user assistance. The present study developed and evaluated deep learning methods for fully-automatic DENSE strain analysis.METHODS: Convolutional neural networks (CNNs) were developed and trained to (a) identify the left-ventricular (LV) epicardial and endocardial borders, (b) identify the anterior right-ventricular (RV)-LV insertion point, and (c) perform phase unwrapping. Subsequent conventional automatic steps were employed to compute strain. The networks were trained using 12,415 short-axis DENSE images from 45 healthy subjects and 19 heart disease patients and were tested using 10,510 images from 25 healthy subjects and 19 patients. Each individual CNN was evaluated, and the end-to-end fully-automatic deep learning pipeline was compared to conventional user-assisted DENSE analysis using linear correlation and Bland Altman analysis of circumferential strain.RESULTS: LV myocardial segmentation U-Nets achieved a DICE similarity coefficient of 0.87±0.04, a Hausdorff distance of 2.7±1.0 pixels, and a mean surface distance of 0.41±0.29 pixels in comparison with manual LV myocardial segmentation by an expert. The anterior RV-LV insertion point was detected within 1.38±0.9 pixels compared to manually annotated data. The phase-unwrapping U-Net had similar or lower mean squared error vs. ground-truth data compared to the conventional path-following method for images with typical signal-to-noise ratio (SNR) or low SNR (p<0.05), respectively. Bland-Altman analyses showed biases of 0.00±0.03 and limits of agreement of -0.04 to 0.05 or better for deep learning-based fully-automatic global and segmental end-systolic circumferential strain vs. conventional user-assisted methods.CONCLUSIONS: Deep learning enables fully-automatic global and segmental circumferential strain analysis of DENSE CMR providing excellent agreement with conventional user-assisted methods. Deep learning-based automatic strain analysis may facilitate greater clinical use of DENSE for the quantification of global and segmental strain in patients with cardiac disease.

    View details for DOI 10.1186/s12968-021-00712-9

    View details for PubMedID 33691739

  • Myofiber strain in healthy humans using DENSE and cDTI. Magnetic resonance in medicine Moulin, K., Croisille, P., Viallon, M., Verzhbinsky, I. A., Perotti, L. E., Ennis, D. B. 2021


    PURPOSE: Myofiber strain, Eff , is a mechanistically relevant metric of cardiac cell shortening and is expected to be spatially uniform in healthy populations, making it a prime candidate for the evaluation of local cardiomyocyte contractility. In this study, a new, efficient pipeline was proposed to combine microstructural cDTI and functional DENSE data in order to estimate Eff in vivo.METHODS: Thirty healthy volunteers were scanned with three long-axis (LA) and three short-axis (SA) DENSE slices using 2D displacement encoding and one SA slice of cDTI. The total acquisition time was 11 minutes ± 3 minutes across volunteers. The pipeline first generates 3D SA displacements from all DENSE slices which are then combined with cDTI data to generate a cine of myofiber orientations and compute Eff . The precision of the post-processing pipeline was assessed using a computational phantom study. Transmural myofiber strain was compared to circumferential strain, Ecc , in healthy volunteers using a Wilcoxon sign rank test.RESULTS: In vivo, computed Eff was found uniform transmurally compared to Ecc (-0.14[-0.15, -0.12] vs -0.18 [-0.20, -0.16], P < .001, -0.14 [-0.16, -0.12] vs -0.16 [-0.17, -0.13], P < .001 and -0.14 [-0.16, -0.12] vs Ecc_C = -0.14 [-0.15, -0.11], P = .002, Eff_C vs Ecc_C in the endo, mid, and epi layers, respectively).CONCLUSION: We demonstrate that it is possible to measure in vivo myofiber strain in a healthy human population in 10 minutes per subject. Myofiber strain was observed to be spatially uniform in healthy volunteers making it a potential biomarker for the evaluation of local cardiomyocyte contractility in assessing cardiovascular dysfunction.

    View details for DOI 10.1002/mrm.28724

    View details for PubMedID 33619807

  • On the impact of vessel wall stiffness on quantitative flow dynamics in a synthetic model of the thoracic aorta. Scientific reports Zimmermann, J. n., Loecher, M. n., Kolawole, F. O., Bäumler, K. n., Gifford, K. n., Dual, S. A., Levenston, M. n., Marsden, A. L., Ennis, D. B. 2021; 11 (1): 6703


    Aortic wall stiffening is a predictive marker for morbidity in hypertensive patients. Arterial pulse wave velocity (PWV) correlates with the level of stiffness and can be derived using non-invasive 4D-flow magnetic resonance imaging (MRI). The objectives of this study were twofold: to develop subject-specific thoracic aorta models embedded into an MRI-compatible flow circuit operating under controlled physiological conditions; and to evaluate how a range of aortic wall stiffness impacts 4D-flow-based quantification of hemodynamics, particularly PWV. Three aorta models were 3D-printed using a novel photopolymer material at two compliant and one nearly rigid stiffnesses and characterized via tensile testing. Luminal pressure and 4D-flow MRI data were acquired for each model and cross-sectional net flow, peak velocities, and PWV were measured. In addition, the confounding effect of temporal resolution on all metrics was evaluated. Stiffer models resulted in increased systolic pressures (112, 116, and 133 mmHg), variations in velocity patterns, and increased peak velocities, peak flow rate, and PWV (5.8-7.3 m/s). Lower temporal resolution (20 ms down to 62.5 ms per image frame) impacted estimates of peak velocity and PWV (7.31 down to 4.77 m/s). Using compliant aorta models is essential to produce realistic flow dynamics and conditions that recapitulated in vivo hemodynamics.

    View details for DOI 10.1038/s41598-021-86174-6

    View details for PubMedID 33758315

  • Using synthetic data generation to train a cardiac motion tag tracking neural network. Medical image analysis Loecher, M., Perotti, L. E., Ennis, D. B. 2021; 74: 102223


    A CNN based method for cardiac MRI tag tracking was developed and validated. A synthetic data simulator was created to generate large amounts of training data using natural images, a Bloch equation simulation, a broad range of tissue properties, and programmed ground-truth motion. The method was validated using both an analytical deforming cardiac phantom and in vivo data with manually tracked reference motion paths. In the analytical phantom, error was investigated relative to SNR, and accurate results were seen for SNR>10 (displacement error <0.3 mm). Excellent agreement was seen in vivo for tag locations (mean displacement difference = -0.02 pixels, 95% CI [-0.73, 0.69]) and calculated cardiac circumferential strain (mean difference = 0.006, 95% CI [-0.012, 0.024]). Automated tag tracking with a CNN trained on synthetic data is both accurate and precise.

    View details for DOI 10.1016/

    View details for PubMedID 34555661

  • Evaluation of Patient Positioning to Mitigate RF-induced Heating of Cardiac Implantable Electronic Devices for Pediatric MRI Exams. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Martinez, J. A., Cork, T. E., Chubb, H., Vasanawala, S., Ennis, D. B. 2021; 2021: 5027-5030


    Pediatric patients with cardiac implantable electronic devices (CIEDs) are generally contraindicated for MRI exams. Previous work in the adult population suggests that RF-induced lead-tip heating strongly depends on the patient's position and orientation within the MRI scanner. The objective of this work was to evaluate the local Specific Absorption Rate (local-SAR) in silico for several pediatric patient positions within the MRI scanner as a method to potentially mitigate RF-heating lead-tip heating of CIEDs.

    View details for DOI 10.1109/EMBC46164.2021.9630640

    View details for PubMedID 34892336

  • A gradient optimization toolbox for general purpose time-optimal MRI gradient waveform design. Magnetic resonance in medicine Loecher, M., Middione, M. J., Ennis, D. B. 2020; 84 (6): 3234-3245


    To introduce and demonstrate a software library for time-optimal gradient waveform optimization with a wide range of applications. The software enables direct on-the-fly gradient waveform design on the scanner hardware for multiple vendors.The open-source gradient optimization (GrOpt) toolbox was implemented in C with both Matlab and Python wrappers. The toolbox enables gradient waveforms to be generated based on a set of constraints that define the features and encodings for a given acquisition. The GrOpt optimization routine is based on the alternating direction method of multipliers (ADMM). Additional constraints enable error corrections to be added, or patient comfort and safety to be adressed. A range of applications and compute speed metrics are analyzed. Finally, the method is implemented and tested on scanners from different vendors.Time-optimal gradient waveforms for different pulse sequences and the constraints that define them are shown. Additionally, the ability to add, arbitrary motion (gradient moment) compensation or limit peripheral nerve stimulation is demonstrated. There exists a trade-off between computation time and gradient raster time, but it was observed that acceptable gradient waveforms could be generated in 1-40 ms. Gradient waveforms generated and run on the different scanners were functionally equivalent, and the images were comparable.GrOpt is an open source toolbox that enables on-the-fly optimization of gradient waveform design, subject to a set of defined constraints. GrOpt was presented for a range of imaging applications, analyzed in terms of computational complexity, and implemented to run on the scanner for a multi-vendor demonstration.

    View details for DOI 10.1002/mrm.28384

    View details for PubMedID 33463724

  • A gradient optimization toolbox for general purpose time-optimal MRI gradient waveform design MAGNETIC RESONANCE IN MEDICINE Loecher, M., Middione, M. J., Ennis, D. B. 2020

    View details for DOI 10.1002/mrm.28384

    View details for Web of Science ID 000545612400001

  • INTRA-MYOCARDIAL ALGINATE HYDROGEL INJECTION ACTS AS A LEFT VENTRICULAR MID-WALL CONSTRAINT IN SWINE. Acta biomaterialia Sack, K. L., Aliotta, E., Choy, J. S., Ennis, D. B., Davies, N., Franz, T., Kassab, G. S., Guccione, J. M. 2020


    Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge about the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To identify the mechanism of action, we examined previously unobtainable measurements of cardiac function from in vivo, ex vivo, and in silico states of clinically relevant heart failure (HF) in large animals. High-resolution ex vivo magnetic resonance imaging and histological data were used along with state-of-the-art subject-specific computational model simulations. Ex vivo data were incorporated in detailed geometric computational models for swine hearts in health (n=5), ischemic HF (n=5), and ischemic HF treated with alginate hydrogel injection therapy (n=5). Hydrogel injection therapy mitigated elongation of sarcomere lengths (1.66 ± 0.15mum [treated] vs. 1.79 ± 0.16mum [untreated], p<0.001). Systolic contractility in treated animals improved substantially (ejection fraction = 43.9 ± 2.6% [treated] vs. 34.7 ± 2.7% [untreated], p<0.01). The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as an LV mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated HF controls without causing negative secondary outcomes to cardiac function. [229 words].

    View details for DOI 10.1016/j.actbio.2020.04.033

    View details for PubMedID 32428678

  • 4D Flow MR Imaging to Improve Microwave Ablation Prediction Models: A Feasibility Study in an InVivo Porcine Liver. Journal of vascular and interventional radiology : JVIR Chiang, J., Loecher, M., Moulin, K., Meloni, M. F., Raman, S. S., McWilliams, J. P., Ennis, D. B., Lee, E. W. 2020


    PURPOSE: To characterize the effect of hepatic vessel flow using 4-dimensional (4D) flow magnetic resonance (MR) imaging and correlate their effect on microwave ablation volumes in an invivo non-cirrhotic porcine liver model.MATERIALS AND METHODS: Microwave ablation antennas were placed under ultrasound guidance in each liver lobe of swine (n= 3 in each animal) for a total of 9 ablations. Pre- and post-ablation 4D flow MR imaging was acquired to quantify flow changes in the hepatic vasculature. Flow measurements, along with encompassed vessel size and vessel-antenna spacing, were then correlated with final ablation volume from segmented MR images.RESULTS: The linear regression model demonstrated that the preablation measurement of encompassed hepatic vein size (beta= -0.80 ±0.25, 95% confidence interval [CI] -1.15 to -0.22; P= .02) was significantly correlated to final ablation zone volume. The addition of hepatic vein flow rate found via 4D flow MRI (beta= -0.83 ± 0.65, 95% CI -2.50 to 0.84; P= .26), and distance from antenna to hepatic vein (beta= 0.26 ±0.26, 95% CI -0.40 to 0.92; P= .36) improved the model accuracy but not significantly so (multivariate adjusted R2= 0.70 vs univariate (vessel size) adjusted R2= 0.63, P= .24).CONCLUSIONS: Hepatic vein size in an encompassed ablation zone was found to be significantly correlated with final ablation zone volume. Although the univariate 4D flow MR imaging-acquired measurements alone were not found to be statistically significant, its addition to hepatic vein size improved the accuracy of the ablation volume regression model. Pre-ablation 4D flow MR imaging of the liver may assist in prospectively optimizing thermal ablation treatment.

    View details for DOI 10.1016/j.jvir.2019.11.034

    View details for PubMedID 32178944

  • Evaluation of a Workflow to Define Low Specific Absorption Rate MRI Protocols for Patients With Active Implantable Medical Devices. Journal of magnetic resonance imaging : JMRI Martinez, J. A., Moulin, K. n., Yoo, B. n., Shi, Y. n., Kim, H. J., Villablanca, P. J., Ennis, D. B. 2020


    MRI exams for patients with MR-conditional active implantable medical devices (AIMDs) are contraindicated unless specific conditions are met. This limits the maximum specific absorption rate (SAR, W/kg). Currently, there is no general framework to guide meeting a lower SAR limit.To design and evaluate a workflow for modifying MRI protocols to whole-body SAR (WB-SAR ≤0.1 W/kg) and local-head SAR (LH-SAR ≤0.3 W/kg) limits while mitigating the impact on image quality and exam time.Prospective.Twenty healthy volunteers on head (n = 5), C-spine (n = 5), T-spine (n = 5), and L-spine (n = 5) with IRB consent.Vendor-provided head, C-spine, T-spine, and L-spine protocols (SARRT ) were modified to meet both low SAR targets (SARLOW ) using the proposed workflow. in vitro SNR and CNR were evaluated with a T1 -T2 phantom. in vivo image quality and clinical acceptability were scored using a 5-point Likert scale for two blinded readers.1.5T/spin-echoes, gradient-echoes.In vitro SNR and CNR values were evaluated with a repeated measures general linear model. in vivo image quality and clinical acceptability were evaluated using a generalized estimating equation analysis (GEE). The two reader's level of agreement was analyzed using Cohen's kappa statistical analysis.Using the workflow, SAR limits were met.0.12 ± 0.02 W/kg, median (SD) values for LH-SAR were 0.12 (0.02) W/kg and WB-SAR: 0.09 (0.01) W/kg. Examination time did not increase ≤2x the initial time. SARRT SNR values were higher and significantly different than SARLOW (P < 0.05). However, no significant difference was observed between the CNR values (value = 0.21). Median (IQR) CNR values were 14.2 (25.0) vs. 15.1 (9.2) for head, 12.1 (16.9) vs. 25.3 (14.2) for C-spine, 81.6 (70.1) vs. 71.0 (26.6) for T-spine, and 51.4 (52.6) vs. 37.7 (27.3) for L-spine. Image quality scores were not significantly different between SARRT and SARLOW (median [SD] scores were 4.0 [0.01] vs. 4.3 [0.2], P > 0.05).The proposed workflow provides guidance for modifying routine MRI exams to achieve low SAR limits. This can benefit patients referred for an MRI exam with low SAR MR-conditional AIMDs.1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020.

    View details for DOI 10.1002/jmri.27044

    View details for PubMedID 31922311

  • Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Stoeck, C. T., Scott, A. D., Ferreira, P. F., Tunnicliffe, E. M., Teh, I., Nielles-Vallespin, S., Moulin, K., Sosnovik, D. E., Viallon, M., Croisille, P., Kozerke, S., Firmin, D. N., Ennis, D. B., Schneider, J. E. 2020; 51 (1): 319–20

    View details for DOI 10.1002/jmri.26767

    View details for Web of Science ID 000530627200031

  • Optimization methods for magnetic resonance imaging gradient waveform design. NMR in biomedicine Middione, M. J., Loecher, M. n., Moulin, K. n., Ennis, D. B. 2020: e4308


    The development and implementation of novel MRI pulse sequences remains challenging and laborious. Gradient waveforms are typically designed using a combination of analytical and ad hoc methods to construct each gradient waveform axis independently. This strategy makes coding the pulse sequence complicated, in addition to being time inefficient. As a consequence, nearly all commercial MRI pulse sequences fail to maximize use of the available gradient hardware or efficiently mitigate physiological effects. This results in expensive MRI systems that underperform relative to their inherent hardware capabilities. To address this problem, a software solution is proposed that incorporates numerical optimization methods into MRI pulse sequence programming. Examples are shown for rotational variant vs. invariant waveform designs, acceleration nulled velocity encoding gradients, and mitigation of peripheral nerve stimulation for diffusion encoding. The application of optimization methods to MRI pulse sequence design incorporates gradient hardware limits and the prescribed MRI protocol parameters (e.g. field-of-view, resolution, gradient moments, and/or b-value) to simultaneously construct time-optimal gradient waveforms. In many cases, the resulting constrained gradient waveform design problem is convex and can be solved on-the-fly on the MRI scanner. The result is a set of multi-axis time-optimal gradient waveforms that satisfy the design constraints, thereby increasing SNR-efficiency. These optimization methods can also be used to mitigate imaging artifacts (e.g. eddy currents) or account for peripheral nerve stimulation. The result of the optimization method is to enable easier pulse sequence gradient waveform design and permit on-the-fly implementation for a range of MRI pulse sequences.

    View details for DOI 10.1002/nbm.4308

    View details for PubMedID 32342560

  • Estimating cardiomyofiber strain in vivo by solving a computational model. Medical image analysis Perotti, L. E., Verzhbinsky, I. A., Moulin, K. n., Cork, T. E., Loecher, M. n., Balzani, D. n., Ennis, D. B. 2020; 68: 101932


    Since heart contraction results from the electrically activated contraction of millions of cardiomyocytes, a measure of cardiomyocyte shortening mechanistically underlies cardiac contraction. In this work we aim to measure preferential aggregate cardiomyocyte ("myofiber") strains based on Magnetic Resonance Imaging (MRI) data acquired to measure both voxel-wise displacements through systole and myofiber orientation. In order to reduce the effect of experimental noise on the computed myofiber strains, we recast the strains calculation as the solution of a boundary value problem (BVP). This approach does not require a calibrated material model, and consequently is independent of specific myocardial material properties. The solution to this auxiliary BVP is the displacement field corresponding to assigned values of myofiber strains. The actual myofiber strains are then determined by minimizing the difference between computed and measured displacements. The approach is validated using an analytical phantom, for which the ground-truth solution is known. The method is applied to compute myofiber strains using in vivo displacement and myofiber MRI data acquired in a mid-ventricular left ventricle section in N=8 swine subjects. The proposed method shows a more physiological distribution of myofiber strains compared to standard approaches that directly differentiate the displacement field.

    View details for DOI 10.1016/

    View details for PubMedID 33383331

  • Probing cardiomyocyte mobility with multi-phase cardiac diffusion tensor MRI. PloS one Moulin, K. n., Verzhbinsky, I. A., Maforo, N. G., Perotti, L. E., Ennis, D. B. 2020; 15 (11): e0241996


    Cardiomyocyte organization and performance underlie cardiac function, but the in vivo mobility of these cells during contraction and filling remains difficult to probe. Herein, a novel trigger delay (TD) scout sequence was used to acquire high in-plane resolution (1.6 mm) Spin-Echo (SE) cardiac diffusion tensor imaging (cDTI) at three distinct cardiac phases. The objective was to characterize cardiomyocyte organization and mobility throughout the cardiac cycle in healthy volunteers.Nine healthy volunteers were imaged with cDTI at three distinct cardiac phases (early systole, late systole, and diastasis). The sequence used a free-breathing Spin-Echo (SE) cDTI protocol (b-values = 350s/mm2, twelve diffusion encoding directions, eight repetitions) to acquire high-resolution images (1.6x1.6x8mm3) at 3T in ~7 minutes/cardiac phase. Helix Angle (HA), Helix Angle Range (HAR), E2 angle (E2A), Transverse Angle (TA), Mean Diffusivity (MD), diffusion tensor eigenvalues (λ1-2-3), and Fractional Anisotropy (FA) in the left ventricle (LV) were characterized.Images from the patient-specific TD scout sequence demonstrated that SE cDTI acquisition was possible at early systole, late systole, and diastasis in 78%, 100% and 67% of the cases, respectively. At the mid-ventricular level, mobility (reported as median [IQR]) was observed in HAR between early systole and late systole (76.9 [72.6, 80.5]° vs 96.6 [85.9, 100.3]°, p<0.001). E2A also changed significantly between early systole, late systole, and diastasis (27.7 [20.8, 35.1]° vs 45.2 [42.1, 49]° vs 20.7 [16.6, 26.4]°, p<0.001).We demonstrate that it is possible to probe cardiomyocyte mobility using multi-phase and high resolution cDTI. In healthy volunteers, aggregate cardiomyocytes re-orient themselves more longitudinally during contraction, while cardiomyocyte sheetlets tilt radially during wall thickening. These observations provide new insights into the three-dimensional mobility of myocardial microstructure during systolic contraction.

    View details for DOI 10.1371/journal.pone.0241996

    View details for PubMedID 33180823

  • T1-Mapping and extracellular volume estimates in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Maforo, N. G., Magrath, P. n., Moulin, K. n., Shao, J. n., Kim, G. H., Prosper, A. n., Renella, P. n., Wu, H. H., Halnon, N. n., Ennis, D. B. 2020; 22 (1): 85


    Cardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD)-a fatal X-linked genetic disorder. Late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling, but it is often a late finding. Current research aims to investigate cardiovascular magnetic resonance (CMR) biomarkers, including native (pre-contrast) T1 and extracellular volume (ECV) to evaluate the early on-set of microstructural remodeling and to grade disease severity. To date, native T1 measurements in DMD have been reported predominantly at 1.5T. This study uses 3T CMR: (1) to characterize global and regional myocardial pre-contrast T1 differences between healthy controls and LGE + and LGE- boys with DMD; and (2) to report global and regional myocardial post-contrast T1 values and myocardial ECV estimates in boys with DMD, and (3) to identify left ventricular (LV) T1-mapping biomarkers capable of distinguishing between healthy controls and boys with DMD and detecting LGE status in DMD.Boys with DMD (N = 28, 13.2 ± 3.1 years) and healthy age-matched boys (N = 20, 13.4 ± 3.1 years) were prospectively enrolled and underwent a 3T CMR exam including standard functional imaging and T1 mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Pre-contrast T1 mapping was performed on all boys, but contrast was administered only to boys with DMD for post-contrast T1 and ECV mapping. Global and segmental myocardial regions of interest were contoured on mid LV T1 and ECV maps. ROI measurements were compared for pre-contrast myocardial T1 between boys with DMD and healthy controls, and for post-contrast myocardial T1 and ECV between LGE + and LGE- boys with DMD using a Wilcoxon rank-sum test. Results are reported as median and interquartile range (IQR). p-Values < 0.05 were considered significant. Receiver Operating Characteristic analysis was used to evaluate a binomial logistic classifier incorporating T1 mapping and LV function parameters in the tasks of distinguishing between healthy controls and boys with DMD, and detecting LGE status in DMD. The area under the curve is reported.Boys with DMD had significantly increased global native T1 [1332 (60) ms vs. 1289 (56) ms; p = 0.004] and increased within-slice standard deviation (SD) [100 (57) ms vs. 74 (27) ms; p = 0.001] compared to healthy controls. LGE- boys with DMD also demonstrated significantly increased lateral wall native T1 [1322 (68) ms vs. 1277 (58) ms; p = 0.001] compared to healthy controls. LGE + boys with DMD had decreased global myocardial post-contrast T1 [565 (113) ms vs 635 (126) ms; p = 0.04] and increased global myocardial ECV [32 (8) % vs. 28 (4) %; p = 0.02] compared to LGE- boys. In all classification tasks, T1-mapping biomarkers outperformed a conventional biomarker, LV ejection fraction. ECV was the best performing biomarker in the task of predicting LGE status (AUC = 0.95).Boys with DMD exhibit elevated native T1 compared to healthy, sex- and age-matched controls, even in the absence of LGE. Post-contrast T1 and ECV estimates from 3T CMR are also reported here for pediatric patients with DMD for the first time and can distinguish between LGE + from LGE- boys. In all classification tasks, T1-mapping biomarkers outperform a conventional biomarker, LVEF.

    View details for DOI 10.1186/s12968-020-00687-z

    View details for PubMedID 33302967

  • Real-time 3T MRI-guided cardiovascular catheterization in a porcine model using a glass-fiber epoxy-based guidewire. PloS one Li, X., Perotti, L. E., Martinez, J. A., Duarte-Vogel, S. M., Ennis, D. B., Wu, H. H. 2020; 15 (2): e0229711


    PURPOSE: Real-time magnetic resonance imaging (MRI) is a promising alternative to X-ray fluoroscopy for guiding cardiovascular catheterization procedures. Major challenges, however, include the lack of guidewires that are compatible with the MRI environment, not susceptible to radiofrequency-induced heating, and reliably visualized. Preclinical evaluation of new guidewire designs has been conducted at 1.5T. Here we further evaluate the safety (device heating), device visualization, and procedural feasibility of 3T MRI-guided cardiovascular catheterization using a novel MRI-visible glass-fiber epoxy-based guidewire in phantoms and porcine models.METHODS: To evaluate device safety, guidewire tip heating (GTH) was measured in phantom experiments with different combinations of catheters and guidewires. In vivo cardiovascular catheterization procedures were performed in both healthy (N = 5) and infarcted (N = 5) porcine models under real-time 3T MRI guidance using a glass-fiber epoxy-based guidewire. The times for each procedural step were recorded separately. Guidewire visualization was assessed by measuring the dimensions of the guidewire-induced signal void and contrast-to-noise ratio (CNR) between the guidewire tip signal void and the blood signal in real-time gradient-echo MRI (specific absorption rate [SAR] = 0.04 W/kg).RESULTS: In the phantom experiments, GTH did not exceed 0.35°C when using the real-time gradient-echo sequence (SAR = 0.04 W/kg), demonstrating the safety of the glass-fiber epoxy-based guidewire at 3T. The catheter was successfully placed in the left ventricle (LV) under real-time MRI for all five healthy subjects and three out of five infarcted subjects. Signal void dimensions and CNR values showed consistent visualization of the glass-fiber epoxy-based guidewire in real-time MRI. The average time (minutes:seconds) for the catheterization procedure in all subjects was 4:32, although the procedure time varied depending on the subject's specific anatomy (standard deviation = 4:41).CONCLUSIONS: Real-time 3T MRI-guided cardiovascular catheterization using a new MRI-visible glass-fiber epoxy-based guidewire is feasible in terms of visualization and guidewire navigation, and safe in terms of radiofrequency-induced guidewire tip heating.

    View details for DOI 10.1371/journal.pone.0229711

    View details for PubMedID 32102092

  • Prostate diffusion MRI with minimal echo time using eddy current nulled convex optimized diffusion encoding. Journal of magnetic resonance imaging : JMRI Zhang, Z., Moulin, K., Aliotta, E., Shakeri, S., Afshari Mirak, S., Hosseiny, M., Raman, S., Ennis, D. B., Wu, H. H. 2019


    BACKGROUND: Prostate diffusion-weighted imaging (DWI) using monopolar encoding is sensitive to eddy-current-induced distortion artifacts. Twice-refocused bipolar encoding suppresses eddy current artifacts, but increases echo time (TE), leading to lower signal-to-noise ratio (SNR). Optimization of the diffusion encoding might improve prostate DWI.PURPOSE: To evaluate eddy current nulled convex optimized diffusion encoding (ENCODE) for prostate DWI with minimal TE.STUDY TYPE: Prospective cohort study.POPULATION: A diffusion phantom, an ex vivo prostate specimen, 10 healthy male subjects (27±3years old), and five prostate cancer patients (62±7years old).FIELD STRENGTH/SEQUENCE: 3T; single-shot spin-echo echoplanar DWI.ASSESSMENT: Eddy-current artifacts, TE, SNR, apparent diffusion coefficient (ADC), and image quality scores from three independent readers were compared between monopolar, bipolar, and ENCODE prostate DWI for standard-resolution (1.6*1.6mm2 , partial Fourier factor [pF] = 6/8) and higher-resolution protocols (1.6*1.6mm2 , pF = off; 1.0* 1.0mm2 , pF = 6/8).STATISTICAL TESTING: SNR and ADC differences between techniques were tested with Kruskal-Wallis and Wilcoxon signed-rank tests (P<0.05 considered significant).RESULTS: Eddy current suppression with ENCODE was comparable to bipolar encoding (mean coefficient of variation across three diffusion directions of 9.4% and 9%). For a standard-resolution protocol, ENCODE achieved similar TE as monopolar and reduced TE by 14 msec compared to bipolar, resulting in 27% and 29% higher mean SNR in prostate transition zone (TZ) and peripheral zone (PZ) (P<0.05) compared to bipolar, respectively. For higher-resolution protocols, ENCODE achieved the shortest TE (67 msec), with 17-21% and 58-70% higher mean SNR compared to monopolar (TE = 77 msec) and bipolar (TE = 102 msec) in PZ and TZ (P<0.05). No significant differences were found in mean TZ (P = 0.91) and PZ ADC (P = 0.94) between the three techniques. ENCODE achieved similar or higher image quality scores than bipolar DWI in patients, with mean intraclass correlation coefficient of 0.77 for overall quality between three independent readers.DATA CONCLUSION: ENCODE minimizes TE (improves SNR) and reduces eddy-current distortion for prostate DWI compared to monopolar and bipolar encoding.LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019.

    View details for DOI 10.1002/jmri.26960

    View details for PubMedID 31625663

  • It's the little things: On the complexity of planar electrode heating in MRI NEUROIMAGE Erhardt, J. B., Lottner, T., Martinez, J., Oezen, A. C., Schuettler, M., Stieglitz, T., Ennis, D. B., Bock, M. 2019; 195: 272–84
  • MRI of Patients with Cardiac Implantable Electronic Devices CURRENT CARDIOVASCULAR IMAGING REPORTS Martinez, J. A., Ennis, D. B. 2019; 12 (7)
  • MRI of Patients with Cardiac Implantable Electronic Devices. Current cardiovascular imaging reports Martinez, J. A., Ennis, D. B. 2019; 12 (7)


    The purpose of this review is to clarify the risks associated with MRI exams for patients with cardiac implantable electronic devices (CIEDs) and to provide information regarding the MRI examination protocol for patients with CIEDs.Several prospective studies evaluated the feasibility of MRI exams for patients with CIEDs and reported no adverse events. These studies suggest that by following a specific MRI examination protocol and monitoring both CIED parameters and the patient's symptoms, an MRI exam can be performed by appropriately trained personnel with an acceptable benefit-to-risk ratio.Both MR unsafe and MR conditional CIEDs are commercially available, but there are no MR safe CIEDs. The potential risks faced by patients with CIEDs during an MRI exam are always present and warrant careful monitoring. Three magnetic fields in the MRI scanner interact with the device in ways that can damage the CIED or harm the patient. Due to safety concerns and out of an abundance of caution, the majority of MRI exams for patients with CIEDs are currently denied. However, when following a specific MRI exam protocol, these risks can be mitigated.

    View details for DOI 10.1007/s12410-019-9502-8

    View details for PubMedID 36117853

    View details for PubMedCentralID PMC9477432

  • Model of Left Ventricular Contraction: Validation Criteria and Boundary Conditions. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Ponnaluri, A. V., Verzhbinsky, I. A., Eldredge, J. D., Garfinkel, A., Ennis, D. B., Perotti, L. E. 2019; 11504: 294–303


    Computational models of cardiac contraction can provide critical insight into cardiac function and dysfunction. A necessary step before employing these computational models is their validation. Here we propose a series of validation criteria based on left ventricular (LV) global (ejection fraction and twist) and local (strains in a cylindrical coordinate system, aggregate cardiomyocyte shortening, and low myocardial compressibility) MRI measures to characterize LV motion and deformation during contraction. These validation criteria are used to evaluate an LV finite element model built from subject-specific anatomy and aggregate cardiomyocyte orientations reconstructed from diffusion tensor MRI. We emphasize the key role of the simulation boundary conditions in approaching the physiologically correct motion and strains during contraction. We conclude by comparing the global and local validation criteria measures obtained using two different boundary conditions: the first constraining the LV base and the second taking into account the presence of the pericardium, which leads to greatly improved motion and deformation.

    View details for DOI 10.1007/978-3-030-21949-9_32

    View details for PubMedID 31231721

  • Highly accelerated, model-free diffusion tensor MRI reconstruction using neural networks MEDICAL PHYSICS Aliotta, E., Nourzadeh, H., Sanders, J., Muller, D., Ennis, D. B. 2019; 46 (4): 1581–91

    View details for DOI 10.1002/mp.13400

    View details for Web of Science ID 000467097200008

  • It's the little things: On the complexity of planar electrode heating in MRI. NeuroImage Erhardt, J. B., Lottner, T., Martinez, J., Ozen, A. C., Schuettler, M., Stieglitz, T., Ennis, D. B., Bock, M. 2019


    Neurological disorders are increasingly analysed and treated with implantable electrodes, and patients with such electrodes are studied with MRI despite the risk of radio-frequency (RF) induced heating during the MRI exam. Recent clinical research suggests that electrodes with smaller diameters of the electrical interface between implant and tissue are beneficial; however, the influence of this electrode contact diameter on RF-induced heating has not been investigated. In this work, electrode contact diameters between 0.3 and 4 mm of implantable electrodes appropriate for stimulation and electrocorticography were evaluated in a 1.5 T MRI system. In situ temperature measurements adapted from the ASTM standard test method were performed and complemented by simulations of the specific absorption rate (SAR) to assess local SAR values, temperature increase and the distribution of dissipated power. Measurements showed temperature changes between 0.8 K and 53 K for different electrode contact diameters, which is well above the legal limit of 1 K. Systematic errors in the temperature measurements are to be expected, as the temperature sensors may disturb the heating pattern near small electrodes. Compared to large electrodes, simulations suggest that small electrodes are subject to less dissipated power, but more localized power density. Thus, smaller electrodes might be classified as safe in current certification procedures but may be more likely to burn adjacent tissue. To assess these local heating phenomena, smaller temperature sensors or new non-invasive temperature sensing methods are needed.

    View details for PubMedID 30935911

  • Time-optimized 4D phase contrast MRI with real-time convex optimization of gradient waveforms and fast excitation methods. Magnetic resonance in medicine Loecher, M., Magrath, P., Aliotta, E., Ennis, D. B. 2019


    PURPOSE: To shorten 4D flow acquisitions by shortening TRs with fast RF pulses and gradient waveforms. Real-time convex optimization is used to generate these gradients waveforms on the scanner.THEORY AND METHODS: RF and slab-select waveforms were shortened with a minimum phase SLR excitation and the time-optimal variable-rate selective excitation method. Real-time convex optimization was used to shorten bipolar and spoiler gradients by finding the shortest gradient waveforms that satisfied constraints on scan parameters, gradient hardware, M0 , M1 , and peripheral nerve stimulation. Waveforms were calculated and TE and/or TR values were compared for a range of scan parameters and compared to a conventional 4D flow sequence. The method was tested in flow phantoms, and in the aorta and neurovasculature of volunteers (N = 10). Additionally, eddy current error was measured in a large phantom.RESULTS: TEs and TRs were shortened by 21-32% and 20-34%, respectively, compared to the conventional sequence over a range of scan parameters. Bland-Altman analysis of 2 flow phantom configurations showed flow rate bias of 0.3 mL/s and limits of agreement (LOA) of [-6.9, 7.5] mL/s for a cardiac phantom and a bias of -0.1 mL/s with LOA = [-0.4, 0.2] mL/s for a neuro phantom. Similar agreement was also seen for flow measurements in volunteers (bias = -1.0 and -0.1 mL/s, LOA = [-34.9, 33.0] and [-0.7, 0.6] mL/s). Measured eddy currents were 39% larger with the CVX + mpVERSE method.CONCLUSION: The real-time optimized 4D flow gradients and fast slab-selection excitation methods produced up to 34% faster TRs with excellent flow measurement agreement compared to a conventional 4D flow sequence.

    View details for DOI 10.1002/mrm.27716

    View details for PubMedID 30859606

  • Highly Accelerated, Model-Free Diffusion Tensor MRI Reconstruction Using Neural Networks. Medical physics Aliotta, E., Nourzadeh, H., Sanders, J., Muller, D., Ennis, D. B. 2019


    PURPOSE: To develop a neural network that accurately performs Diffusion Tensor MRI (DTI) reconstruction from highly accelerated scans.MATERIALS AND METHODS: This retrospective study was conducted using data acquired between 2013 and 2018 and was approved by the local institutional review board. DTI acquired in healthy volunteers (N=10) were used to train a neural network, DiffNet, to reconstruct fractional anisotropy (FA) and mean diffusivity (MD) maps from small subsets of acquired DTI data with between three and 20 diffusion encoding directions. FA and MD maps were then reconstructed in volunteers and in patients with glioblastoma multiforme (GBM, N=12) using both DiffNet and conventional reconstructions. Accuracy and precision were quantified in volunteer scans and compared between reconstructions. The accuracy of tumor delineation was compared between reconstructed patient data by evaluating agreement between DTI-derived tumor volumes and volumes defined by contrast enhanced T1-weighted MRI. Comparisons were performed using areas under the receiver operating characteristic curves (AUC).RESULTS: DiffNet FA reconstructions were more accurate and precise compared with conventional reconstructions for all acceleration factors. DiffNet permitted reconstruction with only three diffusion encoding directions with significantly lower bias than the conventional method using six directions (0.01±0.01 vs. 0.06±0.01, p<0.001). While MD-based tumor delineation was not substantially different with DiffNet (AUC range: 0.888-0.902), DiffNet FA had higher AUC than conventional reconstructions for fixed scan time and achieved similar performance with shorter scans (conventional, six directions: AUC=0.926, DiffNet, three directions: AUC=0.920).CONCLUSION: DiffNet improved DTI reconstruction accuracy, precision, and tumor delineation performance in GBM while permitting reconstruction from only three diffusion encoding directions. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30677141

  • Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging. Journal of magnetic resonance imaging : JMRI Stoeck, C. T., Scott, A. D., Ferreira, P. F., Tunnicliffe, E. M., Teh, I. n., Nielles-Vallespin, S. n., Moulin, K. n., Sosnovik, D. E., Viallon, M. n., Croisille, P. n., Kozerke, S. n., Firmin, D. N., Ennis, D. B., Schneider, J. E. 2019

    View details for PubMedID 31034705

  • Estimating Aggregate Cardiomyocyte Strain Using In Vivo Diffusion and Displacement Encoded MRI. IEEE transactions on medical imaging Verzhbinsky, I. A., Perotti, L. E., Moulin, K. n., Cork, T. E., Loecher, M. n., Ennis, D. B. 2019


    Changes in left ventricular (LV) aggregate cardiomyocyte orientation and deformation underlie cardiac function and dysfunction. As such, in vivo aggregate cardiomyocyte "myofiber" strain (Eff) has mechanistic significance, but currently there exists no established technique to measure in vivo Eff. The objective of this work is to describe and validate a pipeline to compute in vivo Eff from magnetic resonance imaging (MRI) data. Our pipeline integrates LV motion from multi-slice Displacement ENcoding with Stimulated Echoes (DENSE) MRI with in vivo LV microstructure from cardiac Diffusion Tensor Imaging (cDTI) data. The proposed pipeline is validated using an analytical deforming heart-like phantom. The phantom is used to evaluate 3D cardiac strains computed from a widely available, open-source DENSE Image Analysis Tool. Phantom evaluation showed that a DENSE MRI signal-to-noise ratio (SNR) ≥ 20 is required to compute Eff with near-zero median strain bias and within a strain tolerance of 0.06. Circumferential and longitudinal strains are also accurately measured under the same SNR requirements, however, radial strain exhibits a median epicardial bias of -0.10 even in noise-free DENSE data. The validated framework is applied to experimental DENSE MRI and cDTI data acquired in eight (N = 8) healthy swine. The experimental study demonstrated that Eff has decreased transmural variability compared to radial and circumferential strains. The spatial uniformity and mechanistic significance of in vivo Eff make it a compelling candidate for characterization and early detection of cardiac dysfunction.

    View details for DOI 10.1109/TMI.2019.2933813

    View details for PubMedID 31398112

  • Patient Orientation Affects Lead-Tip Heating of Cardiac Active Implantable Medical Devices during MRI. Radiology. Cardiothoracic imaging Martinez, J. A., Serano, P. n., Ennis, D. B. 2019; 1 (3): e190006


    To evaluate changes in patient orientation to mitigate radiofrequency-induced lead-tip heating (LTH) during MRI.LTH was evaluated for device type, lead path, and distance to the isocenter of a 1.5-T MRI system. LTH for 378 conditions in both head-first (HF) and feet-first (FF) orientations was measured for nine MRI-unsafe cardiac active implantable medical devices (AIMDs) placed along three (two anatomic, one planar) left-sided lead paths at nine landmark locations. The devices were exposed to 5 minutes of continuous radiofrequency energy at 4 W/kg whole-body specific absorption rate.LTH was greater in HF than in FF orientation for the planar and one anatomic lead path (P < .05). LTH was significantly affected by lead path, distance to isocenter, and patient orientation (all P < .05), but not by cardiac AIMD device type. Maximum LTH was observed in an HF orientation for the planar lead path when the lead tip was at isocenter (right ventricular [RV] lead: 32.0 °C ± 16.3 [standard deviation], right atrial [RA] lead: 16.1°C ± 9.3). In the FF orientation, LTH was significantly reduced (RV lead: 1.6°C ± 1.4; mean RA lead: 0.5°C ± 1.0; P = .008).LTH for supine FF patient orientations among patients with anterior left-sided cardiac AIMDs can be significantly lower than LTH for supine HF orientations. There was no scenario in which LTH was significantly worse in the FF position. Changing patient orientation is a simple method to reduce radiofrequency-induced LTH.© RSNA, 2019See also the commentary by Litt in this issue.

    View details for DOI 10.1148/ryct.2019190006

    View details for PubMedID 32076667

    View details for PubMedCentralID PMC6735361

  • High-Resolution Ex Vivo Microstructural MRI After Restoring Ventricular Geometry via 3D Printing. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Cork, T. E., Perotti, L. E., Verzhbinsky, I. A., Loecher, M. n., Ennis, D. B. 2019; 11504: 177–86


    Computational modeling of the heart requires accurately incorporating both gross anatomical detail and local microstructural information. Together, these provide the necessary data to build 3D meshes for simulation of cardiac mechanics and electrophysiology. Recent MRI advances make it possible to measure detailed heart motion in vivo, but in vivo microstructural imaging of the heart remains challenging. Consequently, the most detailed measurements of microstructural organization and microanatomical infarct details are obtained ex vivo. The objective of this work was to develop and evaluate a new method for restoring ex vivo ventricular geometry to match the in vivo configuration. This approach aids the integration of high-resolution ex vivo microstructural information with in vivo motion measurements. The method uses in vivo cine imaging to generate surface meshes, then creates a 3D printed left ventricular (LV) blood pool cast and a pericardial mold to restore the ex vivo cardiac geometry to a mid-diastasis reference configuration. The method was evaluated in healthy (N = 7) and infarcted (N = 3) swine. Dice similarity coefficients were calculated between in vivo and ex vivo images for the LV cavity (0.93 ± 0.01), right ventricle (RV) cavity (0.80 ± 0.05), and the myocardium (0.72 ± 0.04). The R 2 coefficient between in vivo and ex vivo LV and RV cavity volumes were 0.95 and 0.91, respectively. These results suggest that this method adequately restores ex vivo geometry to match in vivo geometry. This approach permits a more precise incorporation of high-resolution ex vivo anatomical and microstructural data into computational models that use in vivo data for simulation of cardiac mechanics and electrophysiology.

    View details for DOI 10.1007/978-3-030-21949-9_20

    View details for PubMedID 31432042

    View details for PubMedCentralID PMC6701689

  • Cardiac MRI biomarkers for Duchenne muscular dystrophy. Biomarkers in medicine Magrath, P., Maforo, N., Renella, P., Nelson, S. F., Halnon, N., Ennis, D. B. 2018


    Duchenne muscular dystrophy (DMD) is a fatal inherited genetic disorder that results in progressive muscle weakness and ultimately loss of ambulation, respiratory failure and heart failure. Cardiac MRI (MRI) plays an increasingly important role in the diagnosis and clinical care of boys with DMD and associated cardiomyopathies. Conventional cardiac MRI biomarkers permit measurements of global cardiac function and presence of fibrosis, but changes in these measures are late manifestations. Emerging MRI biomarkers of myocardial function and structure include the estimation of rotational mechanics and regional strain using MRI tagging; T1-mapping; and T2-mapping, a marker of inflammation, edema and fat. These emerging biomarkers provide earlier insights into cardiac involvement in DMD, improving patient care and aiding the evaluation of emerging therapies.

    View details for DOI 10.2217/bmm-2018-0125

    View details for PubMedID 30499689

  • Effect of flow-encoding strength on intravoxel incoherent motion in the liver. Magnetic resonance in medicine Moulin, K., Aliotta, E., Ennis, D. B. 2018


    PURPOSE: To study the impact of variable flow-encoding strength on intravoxel incoherent motion (IVIM) liver imaging of diffusion and perfusion.THEORY: Signal attenuation in DWI arises from (1) intravoxel microvascular blood flow, which depends on the flow-encoding strength alpha (first gradient moment) of the diffusion-encoding waveform, and (2) intravoxel spin diffusion, which depends on the b-value of the diffusion-encoding gradient waveforms alpha and b-value. Both are linked to the diffusion-encoding gradient waveform and conventionally are not independently controlled.METHODS: In this work a convex optimization framework was used to generate gradient waveforms with independent alpha and b-value. Thirty-six unique alpha and b-value sample points from 5 different gradient waveforms were used to reconstruct perfusion fraction (f), coefficient of diffusion (D), and blood velocity standard deviation (Vb ) maps using a recently proposed IVIM model. Faster acquisition strategies were evaluated with 1000 random subsampling strategies of 16, 8, and 4 alpha and b-value. Among the subsampled reconstructions, the sampling schemes that minimized the difference with the fully sampled reconstruction were reported.RESULTS: Healthy volunteers (N = 9) were imaged on a 3T scanner. Liver perfusion and diffusion estimates using the fully sampled IVIM method were f = 0.19 ± 0.06, D = 1.15 ± 0.15 * 10-3 mm2 /s, and Vb = 5.22 ± 3.86 mm/s. No statistical differences were found between the fully sampled and 2-times undersampled reconstruction (f = 0.2 ± 0.07, D = 1.19 ± 0.15 * 10-3 mm2 /s, Vb = 5.79 ± 3.43 mm/s); 4-times undersampled (f = 0.2 ± 0.06, D = 1.15 ± 0.17 * 10-3 mm2 /s, Vb = 4.66 ± 3.61 mm/s), or 8-times undersampled ( f = 0.2 ± 0.06, D = 1.23 ± 0.22 * 10-3 mm2 /s, Vb = 4.99 ± 3.82 mm/s) approaches.CONCLUSION: We demonstrate the IVIM signal's dependence on the b-value, the diffusion-encoding time and the flow-encoding strength and observe in vivo the ballistic regime signature of microperfusion in the liver. This work also demonstrates that using an IVIM model and sampling scheme matched to the ballistic regime, pixel-wise IVIM parameter maps are possible when sampling as few as 4 IVIM signals.

    View details for DOI 10.1002/mrm.27490

    View details for PubMedID 30276853

  • Quantifying precision in cardiac diffusion tensor imaging with second-order motion-compensated convex optimized diffusion encoding MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Moulin, K., Magrath, P., Ennis, D. B. 2018; 80 (3): 1074–87


    To quantify the precision of in vivo cardiac DTI (cDTI) acquired with a spin echo, first- and second-order motion-compensated (M1 M2 ), convex optimized diffusion encoding (CODE) sequence.Free-breathing CODE-M1 M2 cDTI were acquired in healthy volunteers (N = 10) at midsystole and diastole with 10 repeated acquisitions per phase. 95% confidence intervals of uncertainty in reconstructed diffusion tensor eigenvectors ( E→1, E→2, E→3), mean diffusivity (MD), fractional anisotropy (FA), and tensor Mode were measured using a bootstrapping approach. Trends in observed tensor metric uncertainty were evaluated as a function of scan duration, image SNR, cardiac phase, and bulk motion artifacts.For midsystolic scans including 5 signal averages (scan time: ∼5 min), the median myocardial 95% confidence intervals of uncertainties were: E→1: 15.5 ± 1.2°, E→2: 31.2 ± 3.5°, E→3: 21.8 ± 3.1°, MD: 0.38 ± 0.02 × 10-3 mm2 /s, FA: 0.20 ± 0.01, and Mode: 1.10 ± 0.08. Uncertainty in all parameters increased for diastolic scans: E→1: 31.9 ± 7.1°, E→2: 59.6 ± 6.8°, E→3 : 40.5 ± 6.4°, MD: 0.52 ± 0.09 × 10-3 mm2 /s, FA: 0.23 ± 0.01, and Mode: 1.57 ± 0.11. Diastolic cDTI also reported higher MD (MDDIA  = 1.91 ± 0.34 × 10-3 mm2 /s vs. MDSYS  = 1.58 ± 0.09 × 10-3 mm2 /s, P = 8 × 10-3 ) and lower FA values (FADIA  = 0.32 ± 0.06 vs. FASYS  = 0.37 ± 0.03, P = 0.03) .cDTI precision improved with increasing nondiffusion-weighted (b = 0) image SNR, but gains were minimal for SNR ≥ 25 (∼10 averages). cDTI precision was also sensitive to intershot bulk motion artifacts, which led to better precision for midsystolic imaging.

    View details for DOI 10.1002/mrm.27107

    View details for Web of Science ID 000435164500001

    View details for PubMedID 29427349

    View details for PubMedCentralID PMC5980763

  • Microstructural Infarct Border Zone Remodeling in the Post-infarct Swine Heart Measured by Diffusion Tensor MRI FRONTIERS IN PHYSIOLOGY Kung, G. L., Vaseghi, M., Gahm, J. K., Shevtsov, J., Garfinkel, A., Shivkumar, K., Ennis, D. B. 2018; 9: 826


    Introduction: Computational models of the heart increasingly require detailed microstructural information to capture the impact of tissue remodeling on cardiac electromechanics in, for example, hearts with myocardial infarctions. Myocardial infarctions are surrounded by the infarct border zone (BZ), which is a site of electromechanical property transition. Magnetic resonance imaging (MRI) is an emerging method for characterizing microstructural remodeling and focal myocardial infarcts and the BZ can be identified with late gadolinium enhanced (LGE) MRI. Microstructural remodeling within the BZ, however, remains poorly characterized by MRI due, in part, to the fact that LGE and DT-MRI are not always available for the same heart. Diffusion tensor MRI (DT-MRI) can evaluate microstructural remodeling by quantifying the DT apparent diffusion coefficient (ADC, increased with decreased cellularity), fractional anisotropy (FA, decreased with increased fibrosis), and tissue mode (decreased with increased fiber disarray). The purpose of this work was to use LGE MRI in post-infarct porcine hearts (N = 7) to segment remote, BZ, and infarcted myocardium, thereby providing a basis to quantify microstructural remodeling in the BZ and infarcted regions using co-registered DT-MRI. Methods: Chronic porcine infarcts were created by balloon occlusion of the LCx. 6-8 weeks post-infarction, MRI contrast was administered, and the heart was potassium arrested, excised, and imaged with LGE MRI (0.33 × 0.33 × 0.33 mm) and co-registered DT-MRI (1 × 1 × 3 mm). Myocardium was segmented as remote, BZ, or infarct by LGE signal intensity thresholds. DT invariants were used to evaluate microstructural remodeling by quantifying ADC, FA, and tissue mode. Results: The BZ significantly remodeled compared to both infarct and remote myocardium. BZ demonstrated a significant decrease in cellularity (increased ADC), significant decrease in tissue organization (decreased FA), and a significant increase in fiber disarray (decreased tissue mode) relative to remote myocardium (all p < 0.05). Microstructural remodeling in the infarct was similar, but significantly larger in magnitude (all p < 0.05). Conclusion: DT-MRI can identify regions of significant microstructural remodeling in the BZ that are distinct from both remote and infarcted myocardium.

    View details for DOI 10.3389/fphys.2018.00826

    View details for Web of Science ID 000442432000001

    View details for PubMedID 30246802

    View details for PubMedCentralID PMC6113632

  • Velocity reconstruction with nonconvex optimization for low-velocity-encoding phase-contrast MRI MAGNETIC RESONANCE IN MEDICINE Loecher, M., Ennis, D. B. 2018; 80 (1): 42–52


    To introduce and demonstrate a nonconvex optimization method for reconstructing velocity data from low-velocity-encoding (Venc ) phase-contrast MRI data.Solving for velocity values from phase-contrast MRI data was formulated as a nonconvex optimization problem. Weighting was added to account for intravoxel dephasing, and a Laplacian-based regularization was used to account for residual velocity aliasing. The reconstruction was tested with two low-Venc schemes: dual-Venc and a multidirectional high-moment encoding. The reconstruction method was tested in a digital simulation, in flow phantoms, and in healthy volunteers (N = 5).The nonconvex-optimization reconstruction velocity error was lower than the conventional reconstruction in simulations (4.6 versus 3.0 cm/s for multidirectional high moment, 8.3 versus 3.8 cm/s for dual-Venc ) and in flow phantoms (23.9 versus 5.9 cm/s for multidirectional high moment, 15.2 versus 6.4 cm/s for dual-Venc ). Qualitative assessment of velocity fields in all experiments, including healthy volunteers, showed decreased apparent noise in the velocity fields and fewer phase wraps. No additional velocity bias in measured velocities was seen in volunteers with the proposed method.The proposed nonconvex-optimization reconstruction method incorporates additional information to solve for velocities when using any type of low-Venc (high-moment) acquisition. The method reduces the amount of residual phase aliasing, and decreases velocity errors that result from intravoxel dephasing. These improvements allow for more robust acquisitions, and for Venc to be lowered 2 to 4 times relative to conventional acquisitions, thereby increasing the velocity-to-noise ratio. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. Magn Reson Med 80:42-52, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26997

    View details for Web of Science ID 000428703400005

    View details for PubMedID 29130519

  • Construction and Validation of Subject-Specific Biventricular Finite-Element Models of Healthy and Failing Swine Hearts From High-Resolution DT-MRI FRONTIERS IN PHYSIOLOGY Sack, K. L., Aliotta, E., Ennis, D. B., Choy, J. S., Kassab, G. S., Guccione, J. M., Franz, T. 2018; 9: 539


    Predictive computational modeling has revolutionized classical engineering disciplines and is in the process of transforming cardiovascular research. This is particularly relevant for investigating emergent therapies for heart failure, which remains a leading cause of death globally. The creation of subject-specific biventricular computational cardiac models has been a long-term endeavor within the biomedical engineering community. Using high resolution (0.3 × 0.3 × 0.8 mm) ex vivo data, we constructed a precise fully subject-specific biventricular finite-element model of healthy and failing swine hearts. Each model includes fully subject-specific geometries, myofiber architecture and, in the case of the failing heart, fibrotic tissue distribution. Passive and active material properties are prescribed using hyperelastic strain energy functions that define a nearly incompressible, orthotropic material capable of contractile function. These materials were calibrated using a sophisticated multistep approach to match orthotropic tri-axial shear data as well as subject-specific hemodynamic ventricular targets for pressure and volume to ensure realistic cardiac function. Each mechanically beating heart is coupled with a lumped-parameter representation of the circulatory system, allowing for a closed-loop definition of cardiovascular flow. The circulatory model incorporates unidirectional fluid exchanges driven by pressure gradients of the model, which in turn are driven by the mechanically beating heart. This creates a computationally meaningful representation of the dynamic beating of the heart coupled with the circulatory system. Each model was calibrated using subject-specific experimental data and compared with independent in vivo strain data obtained from echocardiography. Our methods produced highly detailed representations of swine hearts that function mechanically in a remarkably similar manner to the in vivo subject-specific strains on a global and regional comparison. The degree of subject-specificity included in the models represents a milestone for modeling efforts that captures realism of the whole heart. This study establishes a foundation for future computational studies that can apply these validated methods to advance cardiac mechanics research.

    View details for DOI 10.3389/fphys.2018.00539

    View details for Web of Science ID 000433372700001

    View details for PubMedID 29896107

    View details for PubMedCentralID PMC5986944

  • Evaluation of the impact of strain correction on the orientation of cardiac diffusion tensors with in vivo and ex vivo porcine hearts MAGNETIC RESONANCE IN MEDICINE Ferreira, P. F., Nielles-Vallespin, S., Scott, A. D., de Silva, R., Kilner, P. J., Ennis, D. B., Auger, D. A., Suever, J. D., Zhong, X., Spottiswoode, B. S., Pennell, D. J., Arai, A. E., Firmin, D. N. 2018; 79 (4): 2205–15


    To evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging.Healthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2 -induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data.Strain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038.The current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required. Magn Reson Med 79:2205-2215, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26850

    View details for Web of Science ID 000425026800039

    View details for PubMedID 28734017

    View details for PubMedCentralID PMC5776058

  • Eddy current-nulled convex optimized diffusion encoding (EN-CODE) for distortion-free diffusion tensor imaging with short echo times MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Moulin, K., Ennis, D. B. 2018; 79 (2): 663–72


    To design and evaluate eddy current-nulled convex optimized diffusion encoding (EN-CODE) gradient waveforms for efficient diffusion tensor imaging (DTI) that is free of eddy current-induced image distortions.The EN-CODE framework was used to generate diffusion-encoding waveforms that are eddy current-compensated. The EN-CODE DTI waveform was compared with the existing eddy current-nulled twice refocused spin echo (TRSE) sequence as well as monopolar (MONO) and non-eddy current-compensated CODE in terms of echo time (TE) and image distortions. Comparisons were made in simulations, phantom experiments, and neuro imaging in 10 healthy volunteers.The EN-CODE sequence achieved eddy current compensation with a significantly shorter TE than TRSE (78 versus 96 ms) and a slightly shorter TE than MONO (78 versus 80 ms). Intravoxel signal variance was lower in phantoms with EN-CODE than with MONO (13.6 ± 11.6 versus 37.4 ± 25.8) and not different from TRSE (15.1 ± 11.6), indicating good robustness to eddy current-induced image distortions. Mean fractional anisotropy values in brain edges were also significantly lower with EN-CODE than with MONO (0.16 ± 0.01 versus 0.24 ± 0.02, P < 1 x 10-5 ) and not different from TRSE (0.16 ± 0.01 versus 0.16 ± 0.01, P = nonsignificant).The EN-CODE sequence eliminated eddy current-induced image distortions in DTI with a TE comparable to MONO and substantially shorter than TRSE. Magn Reson Med 79:663-672, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26709

    View details for Web of Science ID 000419134600006

    View details for PubMedID 28444802

  • Simultaneous measurement of T-2 and apparent diffusion coefficient (T-2+ADC) in the heart with motion-compensated spin echo diffusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Moulin, K., Zhang, Z., Ennis, D. B. 2018; 79 (2): 654–62


    To evaluate a technique for simultaneous quantitative T2 and apparent diffusion coefficient (ADC) mapping in the heart (T2 +ADC) using spin echo (SE) diffusion-weighted imaging (DWI).T2 maps from T2 +ADC were compared with single-echo SE in phantoms and with T2 -prepared (T2 -prep) balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps from T2 +ADC were compared with conventional DWI in phantoms and in vivo. T2 +ADC was also demonstrated in a patient with acute myocardial infarction (MI).Phantom T2 values from T2 +ADC were closer to a single-echo SE reference than T2 -prep bSSFP (-2.3 ± 6.0% vs 22.2 ± 16.3%; P < 0.01), and ADC values were in excellent agreement with DWI (0.28 ± 0.4%). In volunteers, myocardial T2 values from T2 +ADC were significantly shorter than T2 -prep bSSFP (35.8 ± 3.1 vs 46.8 ± 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.) different between T2 +ADC and conventional motion-compensated DWI (1.39 ± 0.18 vs 1.38 ± 0.18 mm2 /ms; P = N.S.). In the patient, T2 and ADC were both significantly elevated in the infarct compared with remote myocardium (T2 : 40.4 ± 7.6 vs 56.8 ± 22.0; P < 0.01; ADC: 1.47 ± 0.59 vs 1.65 ± 0.65 mm2 /ms; P < 0.01).T2 +ADC generated coregistered, free-breathing T2 and ADC maps in healthy volunteers and a patient with acute MI with no cost in accuracy, precision, or scan time compared with DWI. Magn Reson Med 79:654-662, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26705

    View details for Web of Science ID 000419134600005

    View details for PubMedID 28516485

    View details for PubMedCentralID PMC5891215



    In vivo cardiac microstructure acquired using cardiac diffusion tensor imaging (cDTI) is a critical component of patient-specific models of cardiac electrophysiology and mechanics. In order to limit bulk motion artifacts and acquisition time, cDTI microstructural data is acquired at a single cardiac phase necessitating registration to the reference configuration on which the patient-specific computational models are based. Herein, we propose a method to register subject-specific microstructural data to an arbitrary cardiac phase using measured cardiac displacements. We validate our approach using a subject-specific computational phantom based on data from human subjects. Compared to a geometry-based non-rigid registration method, the displacement-based registration leads to improved accuracy (less than 1° versus 10° average median error in cardiomyocyte angular differences) and tighter confidence interval (3° versus 65° average upper limit of the 95% confidence interval).

    View details for Web of Science ID 000455045600108

    View details for PubMedID 30559922

    View details for PubMedCentralID PMC6294325

  • Method for the unique identification of hyperelastic material properties using full-field measures. Application to the passive myocardium material response INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING Perotti, L. E., Ponnaluri, A. S., Krishnamoorthi, S., Balzani, D., Ennis, D. B., Klug, W. S. 2017; 33 (11)


    Quantitative measurement of the material properties (eg, stiffness) of biological tissues is poised to become a powerful diagnostic tool. There are currently several methods in the literature to estimating material stiffness, and we extend this work by formulating a framework that leads to uniquely identified material properties. We design an approach to work with full-field displacement data-ie, we assume the displacement field due to the applied forces is known both on the boundaries and also within the interior of the body of interest-and seek stiffness parameters that lead to balanced internal and external forces in a model. For in vivo applications, the displacement data can be acquired clinically using magnetic resonance imaging while the forces may be computed from pressure measurements, eg, through catheterization. We outline a set of conditions under which the least-square force error objective function is convex, yielding uniquely identified material properties. An important component of our framework is a new numerical strategy to formulate polyconvex material energy laws that are linear in the material properties and provide one optimal description of the available experimental data. An outcome of our approach is the analysis of the reliability of the identified material properties, even for material laws that do not admit unique property identification. Lastly, we evaluate our approach using passive myocardium experimental data at the material point and show its application to identifying myocardial stiffness with an in silico experiment modeling the passive filling of the left ventricle.

    View details for DOI 10.1002/cnm.2866

    View details for Web of Science ID 000415353100004

    View details for PubMedID 28098434

    View details for PubMedCentralID PMC5515704

  • Terahertz Imaging of Cutaneous Edema: Correlation With Magnetic Resonance Imaging in Burn Wounds IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Bajwa, N., Sung, S., Ennis, D. B., Fishbein, M. C., Nowroozi, B. N., Ruan, D., Maccabi, A., Alger, J., St John, M. A., Grundfest, W. S., Taylor, Z. D. 2017; 64 (11): 2682–94


    In vivo visualization and quantification of edema, or 'tissue swelling' following injury, remains a clinical challenge. Herein, we investigate the ability of reflective terahertz (THz) imaging to track changes in tissue water content (TWC)-the direct indicator of edema-by comparison to depth-resolved magnetic resonance imaging (MRI) in a burn-induced model of edema.A partial thickness and full thickness burns were induced in an in vivo rat model to elicit unique TWC perturbations corresponding to burn severity. Concomitant THz surface maps and MRI images of both burn models were acquired with a previously reported THz imaging system and T2-weighted MRI, respectively, over 270 min. Reflectivity was analyzed for the burn contact area in THz images, while proton density (i.e., mobile TWC) was analyzed for the same region at incrementally increasing tissue depths in companion, transverse MRI images. A normalized cross correlation of THz and depth-dependent MRI measurements was performed as a function of time in histologically verified burn wounds.For both burn types, strong positive correlations were evident between THz reflectivity and MRI data analyzed at greater tissue depths (>258 μm). MRI and THz results also revealed biphasic trends consistent with burn edema pathogenesis.This paper offers the first in vivo correlative assessment of mobile TWC-based contrast and the sensing depth of THz imaging.The ability to implement THz imaging immediately following injury, combined with TWC sensing capabilities that compare to MRI, further support THz sensing as an emerging tool to track fluid in tissue.

    View details for DOI 10.1109/TBME.2017.2658439

    View details for Web of Science ID 000413315000018

    View details for PubMedID 28141514

  • Phase-contrast MRI with hybrid one and two-sided flow-encoding and velocity spectrum separation MAGNETIC RESONANCE IN MEDICINE Wang, D., Shao, J., Ennis, D. B., Hu, P. 2017; 78 (1): 182–92


    To develop and evaluate a phase-contrast MRI (PC-MRI) technique with hybrid one and two-sided flow-encoding and velocity spectrum separation (HOTSPA) for accelerated blood flow and velocity measurement.In the HOTSPA technique, the two-sided flow encoding (FE) is used for two FE directions and one-sided is used for the remaining FE direction. Such a temporal modulation of the FE strategy allows for separations of the Fourier velocity spectrum into components for the flow-compensated and the three-directional velocity waveforms, accelerating PC-MRI by encoding three-directional velocities using only two repetition times (TRs) instead of four TRs as in standard PC-MRI. The HOTSPA was evaluated and compared with standard PC-MRI in the common carotid arteries of six healthy volunteers.Total volumetric flow and peak velocity measurements based on HOTSPA and the conventional PC-MRI were in good agreement with a bias of -0.005 mL (-0.1% relative bias error) for total volumetric flow and 1.21 cm/s (1.1% relative bias error) for peak velocity, although the total acquisition time was 50% of the conventional PC-MRI.The proposed HOTSPA technique achieved nearly two-fold acceleration of PC-MRI while maintaining accuracy for total volumetric flow and peak velocity quantification by separating the paired acquisitions in the Fourier velocity spectrum domain. Magn Reson Med 78:182-192, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26366

    View details for Web of Science ID 000403803900018

    View details for PubMedID 27504987

    View details for PubMedCentralID PMC5298945

  • Microstructurally Anchored Cardiac Kinematics by Combining In Vivo DENSE MRI and cDTI. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Perotti, L. E., Magrath, P., Verzhbinsky, I. A., Aliotta, E., Moulin, K., Ennis, D. B. 2017; 10263: 381–91


    Metrics of regional myocardial function can detect the onset of cardiovascular disease, evaluate the response to therapy, and provide mechanistic insight into cardiac dysfunction. Knowledge of local myocardial microstructure is necessary to distinguish between isotropic and anisotropic contributions of local deformation and to quantify myofiber kinematics, a microstructurally anchored measure of cardiac function. Using a computational model we combine in vivo cardiac displacement and diffusion tensor data to evaluate pointwise the deformation gradient tensor and isotropic and anisotropic deformation invariants. In discussing the imaging methods and the model construction, we identify potential improvements to increase measurement accuracy. We conclude by demonstrating the applicability of our method to compute myofiber strain in five healthy volunteers.

    View details for DOI 10.1007/978-3-319-59448-4_36

    View details for PubMedID 29450409

  • Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Ajijola, O. A., Lux, R. L., Khahera, A., Kwon, O., Aliotta, E., Ennis, D. B., Fishbein, M. C., Ardell, J. L., Shivkumar, K. 2017; 312 (3): H608–H621


    The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, n = 12) or anterior myocardial infarction (MI, n = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, P < 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVL nor CVT was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, P < 0.001, and 423 ± 36 vs. 398 ± 36 ms, P = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, P = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHY This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at

    View details for DOI 10.1152/ajpheart.00575.2016

    View details for Web of Science ID 000397808500026

    View details for PubMedID 28087519

    View details for PubMedCentralID PMC5402014

  • Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Nielles-Vallespin, S., Khalique, Z., Ferreira, P. F., de Silva, R., Scott, A. D., Kilner, P., McGill, L., Giannakidis, A., Gatehouse, P. D., Ennis, D., Aliotta, E., Al-Khalil, M., Kellman, P., Mazilu, D., Balaban, R. S., Firmin, D. N., Arai, A. E., Pennell, D. J. 2017; 69 (6): 661–76


    Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function.This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM.In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients.In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001).Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.

    View details for DOI 10.1016/j.jacc.2016.11.051

    View details for Web of Science ID 000396338900009

    View details for PubMedID 28183509

  • Convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted MRI MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Wu, H. H., Ennis, D. B. 2017; 77 (2): 717–29


    To evaluate convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted imaging (DWI).Diffusion-encoding gradient waveforms were designed for a range of b-values and spatial resolutions with and without motion compensation using the CODE framework. CODE, first moment (M1 ) nulled CODE-M1 , and first and second moment (M2 ) nulled CODE-M1 M2 were used to acquire neuro, liver, and cardiac ADC maps in healthy subjects (n=10) that were compared respectively to monopolar (MONO), BIPOLAR (M1  = 0), and motion-compensated (MOCO, M1  + M2  = 0) diffusion encoding.CODE significantly improved the SNR of neuro ADC maps compared with MONO (19.5 ± 2.5 versus 14.5 ± 1.9). CODE-M1 liver ADCs were significantly lower (1.3 ± 0.1 versus 1.8 ± 0.3 × 10-3 mm2 /s, ie, less motion corrupted) and more spatially uniform (6% versus 55% ROI difference) than MONO and had higher SNR than BIPOLAR (SNR = 14.9 ± 5.3 versus 8.0 ± 3.1). CODE-M1 M2 cardiac ADCs were significantly lower than MONO (1.9 ± 0.6 versus 3.8 ± 0.3 x10-3 mm2 /s) throughout the cardiac cycle and had higher SNR than MOCO at systole (9.1 ± 3.9 versus 7.0 ± 2.6) while reporting similar ADCs (1.5 ± 0.2 versus 1.4 ± 0.6 × 10-3 mm2 /s).CODE significantly improved SNR for ADC mapping in the brain, liver and heart, and significantly improved DWI bulk motion robustness in the liver and heart. Magn Reson Med 77:717-729, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26166

    View details for Web of Science ID 000394544700028

    View details for PubMedID 26900872

  • Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy MAGNETIC RESONANCE IN MEDICINE Reyhan, M. L., Wang, Z., Kim, H. J., Halnon, N. J., Finn, J., Ennis, D. B. 2017; 77 (2): 864–69


    Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL).LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method.Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH.Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26137

    View details for Web of Science ID 000394544700045

    View details for PubMedID 26888012

    View details for PubMedCentralID PMC5927592

  • Scar voltage threshold determination using ex vivo magnetic resonance imaging integration in a porcine infarct model: Influence of interelectrode distances and three-dimensional spatial effects of scar HEART RHYTHM Tung, R., Kim, S., Yagishita, D., Vaseghi, M., Ennis, D. B., Ouadah, S., Ajijola, O. A., Bradfield, J. S., Mahapatra, S., Finn, P., Shivkumar, K. 2016; 13 (10): 1993–2002


    Studies analyzing optimal voltage thresholds for scar detection with electroanatomic mapping frequently lack a gold standard for comparison.The purpose of this study was to use a porcine infarct model with ex vivo magnetic resonance imaging (MRI) integration to characterize the relationship between interelectrode spacing and bipolar voltage thresholds and examine the influence of 3-dimensional scar on unipolar voltages.Thirty-two combined endocardial-epicardial electroanatomic maps were created in 8 postinfarct porcine subjects (bipolar 2-mm, 5-mm, and 8-mm interelectrode spacing and unipolar) for comparison with ex vivo MRI. Two thresholds were compared: (1) 95% normal distribution and (2) best fit to MRI. Direct electrogram analysis was performed in regions across from MRI-defined scar and adjacent to scar border zone.A linear increase in optimal thresholds was observed with wider bipole spacing. The 95% thresholds for scar were lower than MRI-matched thresholds with moderate sensitivity for nontransmural scar (54% endo, 63% epi). Unipolar endocardial scar area exceeded MRI-defined scar, resulting in mismatched false scar in 5 of 8 (63%). Endocardial and epicardial unipolar voltages were lower than normal in regions adjacent and across from scar.Variations in interelectrode spacing necessitate tailored bipolar voltage thresholds to optimize scar detection. Statistical 95% thresholds appear to be conservative and not fully sensitive for the detection of scar defined by high-resolution ex vivo MRI. In the presence of endocardial scar, unipolar mapping to quantitatively characterize epicardial scar may be overly sensitive due to 3-dimensional spatial averaging.

    View details for DOI 10.1016/j.hrthm.2016.07.003

    View details for Web of Science ID 000388273900012

    View details for PubMedID 27392944

  • Electrophysiology of Heart Failure Using a Rabbit Model: From the Failing Myocyte to Ventricular Fibrillation PLOS COMPUTATIONAL BIOLOGY Ponnaluri, A. S., Perotti, L. E., Liu, M., Qu, Z., Weiss, J. N., Ennis, D. B., Klug, W. S., Garfinkel, A. 2016; 12 (6): e1004968


    Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we compared the electrical wave propagation in one dimensional cables of healthy and failing cells. The validated cell model was then used to simulate the EP of heart failure in an anatomically accurate biventricular rabbit model. As pacing cycle length decreases, both the normal and failing heart develop T-wave alternans, but only the failing heart shows QRS alternans (although moderate) at rapid pacing. Moreover, T-wave alternans is significantly more pronounced in the failing heart. At rapid pacing, APD maps show areas of conduction block in the failing heart. Finally, accelerated pacing initiated wave reentry and breakup in the failing heart. Further, the onset of VF was not observed with an upregulation of SERCA, a potential drug therapy, using the same protocol. The changes introduced at the cell and tissue level have increased the failing heart's susceptibility to dynamic instabilities and arrhythmias under rapid pacing. However, the observed increase in arrhythmogenic potential is not due to a steepening of the restitution curve (not present in our model), but rather to a novel blocking mechanism.

    View details for DOI 10.1371/journal.pcbi.1004968

    View details for Web of Science ID 000379349700042

    View details for PubMedID 27336310

    View details for PubMedCentralID PMC4919062

  • Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks PLOS COMPUTATIONAL BIOLOGY Newberry, M. G., Ennis, D. B., Savage, V. M. 2015; 11 (8): e1004455


    Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body. Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes. Prominent scaling theories predict that combinations of these exponents explain how metabolic, growth, and other biological rates vary with body size. Nevertheless, direct measurements of individual vessel segments have been limited because existing techniques for measuring vasculature are invasive, time consuming, and technically difficult. We developed software that extracts the length, radius, and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance Angiography. Using data from 20 human subjects, we calculated scaling exponents by four methods-two derived from local properties of branching junctions and two from whole-network properties. Although these methods are often used interchangeably in the literature, we do not find general agreement between these methods, particularly for vessel lengths. Measurements for length of vessels also diverge from theoretical values, but those for radius show stronger agreement. Our results demonstrate that vascular network models cannot ignore certain complexities of real vascular systems and indicate the need to discover new principles regarding vessel lengths.

    View details for DOI 10.1371/journal.pcbi.1004455

    View details for Web of Science ID 000360824500047

    View details for PubMedID 26317654

    View details for PubMedCentralID PMC4552567

  • Left ventricular twist and shear in patients with primary mitral regurgitation JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Wang, Z., Li, M., Kim, H. J., Gupta, H., Lloyd, S. G., Dell'Italia, L. J., Denney, T., Ennis, D. B. 2015; 42 (2): 400–406


    To evaluate the relationship between left ventricular (LV) twist, shear, and twist-per-volume and the severity of mitral regurgitation (MR). Primary MR is a valvular disorder that induces LV dysfunction. There exist several measures of LV rotational mechanics, but it remains unclear which measure of LV dysfunction best accords with the severity of MR. We hypothesized that LV systolic twist-per-volume slope would decrease with increasing severity of MR because of both decreases in rotational mechanics and increases in stroke volumes.Normal subjects (n = 54), moderate MR patients (n = 29), and severe MR patients (n = 54) were studied. Magnetic resonance imaging (MRI) was performed on a 1.5T scanner and grid-tagged LV images were collected at the LV base and LV apex. Measures of LV rotational mechanics were derived from tagged images using Fourier Analysis of STimulated echoes (FAST).Peak systolic twist-per-volume slope was significantly different for all pairwise comparisons (P < 0.0001) and compared to normal subjects (-0.14 ± 0.05°/mL) was decreased in moderate MR (-0.12 ± 0.04°/mL) and further decreased in severe MR (-0.07 ± 0.03°/mL).Peak systolic twist-per-volume slope significantly decreased with increasing severity of MR and is therefore a suitable quantitative imaging biomarker for LV dysfunction in patients with MR.

    View details for DOI 10.1002/jmri.24811

    View details for Web of Science ID 000358258600018

    View details for PubMedID 25408263

  • Phase Contrast MRI with Flow Compensation View Sharing MAGNETIC RESONANCE IN MEDICINE Wang, D., Shao, J., Rapacchi, S., Middione, M. J., Ennis, D. B., Hu, P. 2015; 73 (2): 505-513


    To develop and evaluate a technique for accelerating phase contrast MRI (PC-MRI) acquisitions without significant compromise in flow quantification accuracy.PC-MRI is commonly acquired using interleaved flow-compensated (FC) and flow-encoded (FE) echoes. We hypothesized that FC data, which represent background phase, do not change significantly over time. Therefore, we proposed to undersample the FC data and use an FC view sharing (FCVS) approach to synthesize a composite FC frame for each corresponding FE frame. FCVS was evaluated in a flow phantom and healthy volunteers and compared with a standard FC/FE PC-MRI.The FCVS sequence resulted in an error of 0.0% for forward flow and 2.0% for reverse flow volume when compared with FC/FE PC-MRI in a flow phantom. Measurements in the common carotid arteries showed that the FCVS method had -1.16 cm/s bias for maximum peak velocity and -0.019 mL bias in total flow, when compared with FC/FE with the same temporal resolution, but double the total acquisition time. These results represent ≤1.3% bias error in velocity and volumetric flow quantification.FCVS can accelerate PC-MRI acquisitions while maintaining flow and velocity measurement accuracy when there is limited temporal variation in the FC data.

    View details for DOI 10.1002/mrm.25133

    View details for Web of Science ID 000348139500008

    View details for PubMedID 24532480

    View details for PubMedCentralID PMC4459783

  • Free-breathing variable flip angle balanced SSFP cardiac cine imaging with reduced SAR at 3T. Magnetic resonance in medicine Srinivasan, S. n., Kroeker, R. M., Gabriel, S. n., Plotnik, A. n., Godinez, S. R., Hu, P. n., Halnon, N. n., Finn, J. P., Ennis, D. B. 2015


    To develop a free-breathing variable flip angle (VFA) balanced steady-state free precession (bSSFP) cardiac cine imaging technique with reduced specific absorption rate (SAR) at 3 Tesla.Free-breathing VFA (FB-VFA) images in the short-axis and four-chamber views were acquired using an optimal VFA scheme, then compared with conventional breath-hold constant flip angle (BH-CFA) acquisitions. Two cardiac MRI experts used a 5-point scale to score images from healthy subjects (N = 10). The left ventricular ejection fraction, end diastolic volume (LVEDV), end systolic volume, stroke volume (LVSV), and end diastolic myocardial mass (LVEDM) were determined by manual contour analysis for BH-CFA and FB-VFA. A pilot evaluation of FB-VFA was performed in one patient with Duchenne muscular dystrophy.FB-VFA SAR was 25% lower than BH-CFA with similar blood-myocardium contrast. The qualitative FB-VFA score was lower than the BH-CFA for the short-axis (3.1 ± 0.5 versus 4.3 ± 0.8; P < 0.05) and the four-chamber view (3.4 ± 0.4 versus 4.6 ± 0.6; P < 0.05). The LVEDV and the LVSV were 5% and 12% larger (P < 0.05) for FB-VFA compared with BH-CFA. There was no difference in LVEDM.FB-VFA bSSFP cardiac cine imaging decreased the SAR at 3T with image quality sufficient to perform cardiac functional analysis. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.26011

    View details for PubMedID 26509846

  • Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology PLOS ONE Krishnamoorthi, S., Perotti, L. E., Borgstrom, N. P., Ajijola, O. A., Frid, A., Ponnaluri, A. V., Weiss, J. N., Qu, Z., Klug, W. S., Ennis, D. B., Garfinkel, A. 2014; 9 (12): e114494


    We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

    View details for DOI 10.1371/journal.pone.0114494

    View details for Web of Science ID 000346611400048

    View details for PubMedID 25493967

    View details for PubMedCentralID PMC4262432

  • Convex Gradient Optimization for Increased Spatiotemporal Resolution and Improved Accuracy in Phase Contrast MRI MAGNETIC RESONANCE IN MEDICINE Middione, M. J., Wu, H. H., Ennis, D. B. 2014; 72 (6): 1552-1564


    To evaluate convex gradient optimization (CVX) for increased spatiotemporal resolution and improved accuracy for phase-contrast MRI (PC-MRI).A conventional flow-compensated and flow-encoded (FCFE) PC-MRI sequence was compared with a CVX PC-MRI sequence using numerical simulations, flow phantom experiments, and in vivo experiments. Flow measurements within the ascending aorta, main pulmonary artery, and right/left pulmonary arteries of normal volunteers (N = 10) were acquired at 3T and analyzed using a conventional FCFE sequence and a CVX sequence with either higher spatial resolution or higher temporal resolution. All sequences mitigated chemical shift-induced phase errors and used equivalent breath-hold durations.Chemical shift-optimized PC-MRI has increased sequence efficiency when using CVX, which can provide either higher spatial or higher temporal resolution compared with conventional FCFE PC-MRI. Numerical simulations, flow phantom experiments, and in vivo experiments indicate that CVX measurements of total flow and peak velocity are increased and more accurate when compared with FCFE.CVX PC-MRI increases sequence efficiency while reducing chemical shift-induced phase errors. This can be used to provide either higher spatial or higher temporal resolution than conventional chemical shift-mitigated PC-MRI methods to provide more accurate measurements of blood flow and peak velocity.

    View details for DOI 10.1002/mrm.25059

    View details for Web of Science ID 000344798300008

    View details for PubMedID 24347040

  • Velocity Encoding with the Slice Select Refocusing Gradient for Faster Imaging and Reduced Chemical Shift-Induced Phase Errors MAGNETIC RESONANCE IN MEDICINE Middione, M. J., Thompson, R. B., Ennis, D. B. 2014; 71 (6): 2014-2023


    To investigate a novel phase-contrast MRI velocity-encoding technique for faster imaging and reduced chemical shift-induced phase errors.Velocity encoding with the slice select refocusing gradient achieves the target gradient moment by time shifting the refocusing gradient, which enables the use of the minimum in-phase echo time (TE) for faster imaging and reduced chemical shift-induced phase errors. Net forward flow was compared in 10 healthy subjects (N = 10) within the ascending aorta (aAo), main pulmonary artery (PA), and right/left pulmonary arteries (RPA/LPA) using conventional flow compensated and flow encoded (401 Hz/px and TE = 3.08 ms) and slice select refocused gradient velocity encoding (814 Hz/px and TE = 2.46 ms) at 3 T.Improved net forward flow agreement was measured across all vessels for slice select refocused gradient compared to flow compensated and flow encoded: aAo vs. PA (1.7% ± 1.9% vs. 5.8% ± 2.8%, P = 0.002), aAo vs. RPA + LPA (2.1% ± 1.7% vs. 6.0% ± 4.3%, P = 0.03), and PA vs. RPA + LPA (2.9% ± 2.1% vs. 6.1% ± 6.3%, P = 0.04), while increasing temporal resolution (35%) and signal-to-noise ratio (33%).Slice select refocused gradient phase-contrast MRI with a high receiver bandwidth and minimum in-phase TE provides more accurate and less variable flow measurements through the reduction of chemical shift-induced phase errors and a reduced TE/repetition time, which can be used to increase the temporal/spatial resolution and/or reduce breath hold durations.

    View details for DOI 10.1002/mrm.24861

    View details for Web of Science ID 000336260900009

    View details for PubMedID 23836543

  • Modeling and incorporating cardiac-induced lung tissue motion in a breathing motion model MEDICAL PHYSICS White, B. M., Santhanam, A., Thomas, D., Min, Y., Lamb, J. M., Neylon, J., Jani, S., Gaudio, S., Srinivasan, S., Ennis, D., Low, D. A. 2014; 41 (4)


    The purpose of this work is to develop a cardiac-induced lung motion model to be integrated into an existing breathing motion model.The authors' proposed cardiac-induced lung motion model represents the lung tissue's specific response to the subject's cardiac cycle. The model is mathematically defined as a product of a converging polynomial function h of the cardiac phase (c) and the maximum displacement y(X0) of each voxel (X0) among all the cardiac phases. The function h(c) was estimated from cardiac-gated MR imaging of ten healthy volunteers using an Akaike Information Criteria optimization algorithm. For each volunteer, a total of 24 short-axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12-15 s breath-hold maneuvers. Each view contained 30 temporal frames of equal time-duration beginning with the end-diastolic cardiac phase. The frames in each of the planar views were resampled to create a set of three-dimensional (3D) anatomical volumes representing thoracic anatomy at different cardiac phases. A 3D multiresolution optical flow deformable image registration algorithm was used to quantify the difference in tissue position between the end-diastolic cardiac phase and the remaining cardiac phases. To account for image noise, voxel displacements whose maximum values were less than 0.3 mm, were excluded. In addition, the blood vessels were segmented and excluded in order to eliminate registration artifacts caused by blood-flow.The average cardiac-induced lung motions for displacements greater than 0.3 mm were found to be 0.86 ± 0.74 and 0.97 ± 0.93 mm in the left and right lungs, respectively. The average model residual error for the ten healthy volunteers was found to be 0.29 ± 0.08 mm in the left lung and 0.38 ± 0.14 mm in the right lung for tissue displacements greater than 0.3 mm. The relative error decreased with increasing cardiac-induced lung tissue motion. While the relative error was > 60% for submillimeter cardiac-induced lung tissue motion, the relative error decreased to < 5% for cardiac-induced lung tissue motion that exceeded 10 mm in displacement.The authors' studies implied that modeling and including cardiac-induced lung motion would improve breathing motion model accuracy for tissues with cardiac-induced motion greater than 0.3 mm.

    View details for DOI 10.1118/1.4866888

    View details for Web of Science ID 000334287000041

    View details for PubMedID 24694158

    View details for PubMedCentralID PMC3987767

  • Accelerating Dynamic Magnetic Resonance Imaging (MRI) for Lung Tumor Tracking Based on Low-Rank Decomposition in the Spatial-Temporal Domain: A Feasibility Study Based on Simulation and Preliminary Prospective Undersampled MRI INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sarma, M., Hu, P., Rapacchi, S., Ennis, D., Thomas, A., Lee, P., Kupelian, P., Sheng, K. 2014; 88 (3): 723–31


    To evaluate a low-rank decomposition method to reconstruct down-sampled k-space data for the purpose of tumor tracking.Seven retrospective lung cancer patients were included in the simulation study. The fully-sampled k-space data were first generated from existing 2-dimensional dynamic MR images and then down-sampled by 5 × -20 × before reconstruction using a Cartesian undersampling mask. Two methods, a low-rank decomposition method using combined dynamic MR images (k-t SLR based on sparsity and low-rank penalties) and a total variation (TV) method using individual dynamic MR frames, were used to reconstruct images. The tumor trajectories were derived on the basis of autosegmentation of the resultant images. To further test its feasibility, k-t SLR was used to reconstruct prospective data of a healthy subject. An undersampled balanced steady-state free precession sequence with the same undersampling mask was used to acquire the imaging data.In the simulation study, higher imaging fidelity and low noise levels were achieved with the k-t SLR compared with TV. At 10 × undersampling, the k-t SLR method resulted in an average normalized mean square error <0.05, as opposed to 0.23 by using the TV reconstruction on individual frames. Less than 6% showed tracking errors >1 mm with 10 × down-sampling using k-t SLR, as opposed to 17% using TV. In the prospective study, k-t SLR substantially reduced reconstruction artifacts and retained anatomic details.Magnetic resonance reconstruction using k-t SLR on highly undersampled dynamic MR imaging data results in high image quality useful for tumor tracking. The k-t SLR was superior to TV by better exploiting the intrinsic anatomic coherence of the same patient. The feasibility of k-t SLR was demonstrated by prospective imaging acquisition and reconstruction.

    View details for DOI 10.1016/j.ijrobp.2013.11.217

    View details for Web of Science ID 000331726300030

    View details for PubMedID 24412430

    View details for PubMedCentralID PMC3941205

  • Intra- and Interscan Reproducibility Using Fourier Analysis of STimulated Echoes (FAST) for the Rapid and Robust Quantification of Left Ventricular Twist JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Kim, H. J., Brown, M. S., Ennis, D. B. 2014; 39 (2): 463–68


    To assess the intra- and interscan reproducibility of LV twist using FAST. Assessing the reproducibility of the measurement of new MRI biomarkers is an important part of validation. Fourier Analysis of STimulated Echoes (FAST) is a new MRI tissue tagging method that has recently been shown to compare favorably with conventional estimates of left ventricular (LV) twist from cardiac tagged images, but with significantly reduced user interaction time.Healthy volunteers (N = 10) were scanned twice using FAST over 1 week. On day 1, two measurements of LV twist were collected for intrascan comparisons. Measurements for LV twist were again collected on day 8 for interscan assessment. LV short-axis tagged images were acquired on a 3 Tesla (T) scanner to ensure detectability of tags during early and mid-diastole. Peak LV twist is reported as mean ± SD. Reproducibility was assessed using the concordance correlation coefficient (CCC) and the repeatability coefficient (RC) (95% confidence interval [CI] range).Mean peak twist measurements were 13.4 ± 4.3° (day 1, scan 1), 13.6 ± 3.7° (day 1, scan 2), and 13.0 ± 2.7° (day 8). Bland-Altman analysis resulted in intra- and interscan bias and 95% CI of -0.6° [-1.0°, 1.6°] and 1.4° (-1.0°, 3.0°), respectively. The Bland-Altman RC for peak LV twist was 2.6° and 4.0° for intra- and interscan, respectively. The CCC was 0.9 and 0.6 for peak LV twist for intra- and interscan, respectively.FAST is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist that demonstrates high intrascan and moderate interscan reproducibility in preliminary studies.

    View details for DOI 10.1002/jmri.24162

    View details for Web of Science ID 000329753400027

    View details for PubMedID 23633244

    View details for PubMedCentralID PMC3751999

  • Device artifact reduction for magnetic resonance imaging of patients with implantable cardioverter-defibrillators and ventricular tachycardia: Late gadolinium enhancement correlation with electroanatomic mapping HEART RHYTHM Stevens, S. M., Tung, R., Rashid, S., Gima, J., Cote, S., Pavez, G., Khan, S., Ennis, D. B., Finn, J., Boyle, N., Shivkumar, K., Hu, P. 2014; 11 (2): 289–98


    Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) of ventricular scar has been shown to be accurate for detection and characterization of arrhythmia substrates. However, the majority of patients referred for ventricular tachycardia (VT) ablation have an implantable cardioverter-defibrillator (ICD), which obscures image integrity and the clinical utility of MRI.The purpose of this study was to develop and validate a wideband LGE MRI technique for device artifact removal.A novel wideband LGE MRI technique was developed to allow for improved scar evaluation on patients with ICDs. The wideband technique and the standard LGE MRI were tested on 18 patients with ICDs. VT ablation was performed in 13 of 18 patients with either endocardial and/or epicardial approach and the correlation between the scar identified on MRI and electroanatomic mapping (EAM) was analyzed.Hyperintensity artifact was present in 16 of 18 of patients using standard MRI, which was eliminated using the wideband LGE and allowed for MRI interpretation in 15 of 16 patients. All patients had ICD lead characteristics confirmed as unchanged post-MRI and had no adverse events. LGE scar was seen in 11 of 18 patients. Among the 15 patients in whom wideband LGE allowed visualization of myocardium, 10 had LGE scar and 5 had normal myocardium in the regions with image artifacts when using the standard LGE. The left ventricular scar size measurements using wideband MRI and EAM were correlated with R(2) = 0.83 and P = .00003.Wideband LGE MRI improves the ability to visualize myocardium for clinical interpretation, which correlated well with EAM findings during VT ablation.

    View details for DOI 10.1016/j.hrthm.2013.10.032

    View details for Web of Science ID 000330189700019

    View details for PubMedID 24140812

    View details for PubMedCentralID PMC3946910

  • Off-Resonance Insensitive Complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) for Quantification of Left Ventricular Twist JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Natsuaki, Y., Ennis, D. B. 2014; 39 (2): 339–45


    To evaluate Off Resonance Insensitive Complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) and Fourier Analysis of STimulated echoes (FAST) for the quantification of left ventricular (LV) systolic and diastolic function and compare it with the previously validated FAST+SPAMM technique.LV short-axis tagged images were acquired with ORI-CSPAMM and SPAMM in healthy volunteers (n = 13). The FAST method was used to automatically estimate LV systolic and diastolic twist parameters from rotation of the stimulated echo and stimulated anti-echo about the middle of k-space subsequent to ∼3 min of user interaction.There was no significant difference between measures obtained for FAST+ORI-CSPAMM and FAST+SPAMM for mean peak twist (12.9 ± 3.4° versus 11.9 ± 4.0°; P = 0.4), torsion (3.3 ± 0.9°/cm versus 2.9 ± 1.0°/cm, P = 0.3), circumferential-longitudinal shear angle (9.1 ± 3.0° versus 8.2 ± 3.4°, P = 0.3), twisting rate (79.6 ± 20.2°/s versus 68.2 ± 23.4°/s, P = 0.1), untwisting rate (-117.5 ± 31.4°/s versus -106.6 ± 32.4°/s, P = 0.3), normalized untwisting rate (-9.3 ± 2.0/s versus -9.9 ± 4.4/s, P = 0.7), and time of peak twist (281 ± 18 ms versus 293 ± 25 ms, P = 0.04). FAST+ORI-CSPAMM also provided measures of duration of untwisting (148 ± 21 ms) and the ratio of rapid untwisting to peak twist (0.9 ± 0.3). Bland-Altman analysis of FAST+ORI-CSPAMM and FAST+SPAMM twist data demonstrates excellent agreement with a bias of -0.1° and 95% confidence intervals of (-1.0°, 3.2°).FAST+ORI-CSPAMM is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist and torsion. ORI-CSPAMM corrects off-resonance accrued during tagging preparation and readout and visibly removes chemical shift from the tagging pattern, which confers greater robustness to the derived quantitative measures.

    View details for DOI 10.1002/jmri.24154

    View details for Web of Science ID 000329753400012

    View details for PubMedID 23625854

    View details for PubMedCentralID PMC3732806

  • Optimal flip angle for high contrast balanced SSFP cardiac cine imaging. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Srinivasan, S. n., Ennis, D. B. 2014


    To determine the optimal flip angle (FA) for cardiac cine imaging that maximizes myocardial signal and blood-myocardium contrast.Bloch equation simulations of stationary myocardium and flowing blood with an imperfect slice profile were compared to in vivo measurements of blood and myocardium signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) in healthy subjects (N = 10) in the short-axis and four-chamber views and in patients (N = 7) in the three-chamber imaging plane.Left ventricular (LV) and right ventricular (RV) blood SNR and blood-myocardium CNR increases with increasing FA up to ≈105° in the short-axis view. A similar trend is seen in the RV four-chamber view, but a marked SNR difference between the LV and RV blood appears for FA>75°, especially during systole. Notable RV and LV SNR and CNR differences are also evident in the three-chamber view due to the predominant LV in-plane flow versus RV through-plane flow.Very high blood-myocardium CNR can be obtained with a FA of ≈105° in the short-axis plane and ≈75° in the three-chamber and four-chamber imaging planes. However, if through-plane flow is limited, as may occur for patients with low ejection fraction or low heart rates, then the FA may be limited to ≈ 75°. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.25228

    View details for PubMedID 24700652

  • The effects of noise over the complete space of diffusion tensor shape MEDICAL IMAGE ANALYSIS Gahm, J., Kindlmann, G., Ennis, D. B. 2014; 18 (1): 197–210


    Diffusion tensor magnetic resonance imaging (DT-MRI) is a technique used to quantify the microstructural organization of biological tissues. Multiple images are necessary to reconstruct the tensor data and each acquisition is subject to complex thermal noise. As such, measures of tensor invariants, which characterize components of tensor shape, derived from the tensor data will be biased from their true values. Previous work has examined this bias, but over a narrow range of tensor shape. Herein, we define the mathematics for constructing a tensor from tensor invariants, which permits an intuitive and principled means for building tensors with a complete range of tensor shape and salient microstructural properties. Thereafter, we use this development to evaluate by simulation the effects of noise on characterizing tensor shape over the complete space of tensor shape for three encoding schemes with different SNR and gradient directions. We also define a new framework for determining the distribution of the true values of tensor invariants given their measures, which provides guidance about the confidence the observer should have in the measures. Finally, we present the statistics of tensor invariant estimates over the complete space of tensor shape to demonstrate how the noise sensitivity of tensor invariants varies across the space of tensor shape as well as how the imaging protocol impacts measures of tensor invariants.

    View details for DOI 10.1016/

    View details for Web of Science ID 000328802900014

    View details for PubMedID 24239734

  • A framework for modeling and visualizing cardiovascular deformation under normal and altered circulatory conditions. Studies in health technology and informatics Santhanam, A., Benharash, P., Frank, P., White, B., Min, Y., Ennis, D., Kupelian, P., Dutson, E. 2014; 196: 378–83


    The aim of this paper is to model and visualize cardiovascular deformations in order to better understand vascular movements inside the lung and heart caused by abnormal cardiac conditions. The modeling was performed in two steps: first step involved modeling the cardiac output taking into account of the heart rate and preload blood volume, contractility and systematic vascular resistance. The second step involved deforming a 3D cine cardiac gated Magnetic Resonance Volume to the corresponding cardiac output. Cardiac-gated MR imaging of 4 healthy volunteers were acquired. For each volunteer, a total of 24 short-axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12-15 second breath-hold maneuvers. A 3D multi-resolution optical flow deformable image registration algorithm was used to quantify the volumetric cardiovascular displacements for known cardiac outputs. Results show that a real-time visualization of the vascular deformations inside both the lung as well as the heart can be seen for different cardiac outputs representing normal and abnormal cardiac conditions.

    View details for PubMedID 24732540

  • In vivo Confirmation of Hydration Based Contrast Mechanisms for Terahertz Medical Imaging using MRI Bajwa, N., Sung, S., Garritano, J., Nowroozi, B., Tewari, P., Ennis, D. B., Alger, J., Grundfest, W., Taylor, Z., Razeghi, M., Baranov, A. N., Zavada, J. M., Pavlidis, D. SPIE-INT SOC OPTICAL ENGINEERING. 2014

    View details for DOI 10.1117/12.2060115

    View details for Web of Science ID 000348191300020

  • Fast 3D T2 -weighted imaging using variable flip angle transition into driven equilibrium (3D T2 -TIDE) balanced SSFP for prostate imaging at 3T. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Srinivasan, S. n., Wu, H. H., Sung, K. n., Margolis, D. J., Ennis, D. B. 2014


    Three-dimensional (3D) T2 -weighted fast spin echo (FSE) imaging of the prostate currently requires long acquisition times. Our objective was to develop a fast 3D T2 -weighted sequence for prostate imaging at 3T using a variable flip angle transition into driven equilibrium (T2 -TIDE) scheme.3D T2 -TIDE uses interleaved spiral-out phase encode ordering to efficiently sample the ky -kz phase encodes and also uses the transient balanced steady-state free precession signal to acquire the center of k-space for T2 -weighted imaging. Bloch simulations and images from 10 healthy subjects were acquired to evaluate the performance of 3D T2 -TIDE compared to 3D FSE.3D T2 -TIDE images were acquired in 2:54 minutes compared to 7:02 minutes for 3D FSE with identical imaging parameters. The signal-to-noise ratio (SNR) efficiency was significantly higher for 3D T2 -TIDE compared to 3D FSE in nearly all tissues, including periprostatic fat (45 ± 12 vs. 31 ± 7, P < 0.01), gluteal fat (48 ± 8 vs. 41 ± 10, P = 0.12), right peripheral zone (20 ± 4 vs. 16 ± 8, P = 0.12), left peripheral zone (17 ± 2 vs. 12 ± 3, P < 0.01), and anterior fibromuscular stroma (12 ± 4 vs. 4 ± 2, P < 0.01).3D T2 -TIDE images of the prostate can be acquired quickly with SNR efficiency that exceeds that of 3D FSE. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.25430

    View details for PubMedID 25195659

  • Complementary radial tagging for improved myocardial tagging contrast. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Wang, Z. n., Nasiraei-Moghaddam, A. n., Reyhan, M. L., Srinivasan, S. n., Finn, J. P., Ennis, D. B. 2014


    To develop and evaluate complementary radial tagging (CRT) for improved myocardial tagging contrast.We sought to develop and evaluate CRT, which aims to preserve the radial tag contrast throughout the cardiac cycle. Similar to complementary spatial modulation of magnetization, CRT acquires two sets of images with a phase shift in the tag pattern. The combination of a ramped imaging flip angle and image subtraction enhances tag contrast throughout the cardiac cycle. The proposed CRT technique uses a small table shift away from the isocenter to improve the uniformity of the radial tag pattern. We provide a mathematical solution for the optimal table shift and validate the solution in using a retrospective analysis of images from 500 patients in the Cardiac Atlas Project database.CRT simulations, phantom experiments, and in vivo images all demonstrate the improved tag contrast of CRT compared to RT. The retrospective evaluation demonstrated that acceptable CRT images could be acquired in over 98% of the clinical exams.The CRT technique improves radial tag contrast throughout the cardiac cycle and should produce high quality tag patterns in nearly all patients. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.25259

    View details for PubMedID 24824305

  • Effect of stellate ganglia stimulation on global and regional left ventricular function as assessed by speckle tracking echocardiography AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Zhou, W., Yamakawa, K., Benharash, P., Ajijola, O., Ennis, D., Hadaya, J., Vaseghi, M., Shivkumar, K., Mahajan, A. 2013; 304 (6): H840–H847


    Left ventricular (LV) twist mechanics and regional strain during cardiac sympathetic efferent activation are poorly understood. The purpose of this study was to compare the effects of left stellate ganglia (LSG) and right stellate ganglia (RSG) stimulation on cardiac twist/untiwst mechanics and regional strain. In nine pigs, echocardiographic imaging and LV pressure-volume measurements were performed before and during unilateral and bilateral stellate ganglion stimulation. LSG and RSG stimulation significantly augmented LV end-systolic pressure by 24% and 22% (P < 0.01), maximal rate of LV pressure change by 167% and 165% (P < 0.01), and time constant of LV relaxation by 20% and 12% (P < 0.01), respectively. RSG stimulation resulted in a greater chronotropic response than LSG stimulation (RSG: 68% vs. LSG: 12%, P < 0.01). Both LSG and RSG stimulation significantly increased global epicardial and endocardial LV rotation and diastolic untwisting rate and reduced the time to peak rotation (P < 0.05). However, LSG stimulation predominantly increased radial and circumferential strain in the LV inferoseptal, inferior, posterior, and lateral regions, whereas RSG stimulation primarily increased radial and circumferential strain in the anteroseptal, anterior, and lateral LV regions. Stimulation of both stellate ganglia led to a uniform increase in all LV segments. Our data suggest that LSG and RSG stimulation lead to a global increase in LV twist, driven by distinct regional strain heterogeneity that may result from myocardial innervation from the LSG and RSG. These findings provide a better understanding of the global and regional functional consequences of regional myocardial innervation from the LSG and RSG.

    View details for DOI 10.1152/ajpheart.00695.2012

    View details for Web of Science ID 000316206400008

    View details for PubMedID 23335795

    View details for PubMedCentralID PMC3602776

  • Quantitative assessment of systolic and diastolic left ventricular twist using Fourier Analysis of Stimulated echoes (FAST) and CSPAMM JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Ennis, D. B. 2013; 37 (3): 678–83


    To evaluate Fourier Analysis of Stimulated echoes (FAST) and CSPAMM for the quantification of left ventricular (LV) systolic and diastolic function and compare it with the previously validated FAST+SPAMM technique.LV short-axis tagged images were acquired with CSPAMM and SPAMM in healthy volunteers (n = 13). The FAST method was used to automatically estimate LV systolic and diastolic twist parameters from rotation of the stimulated echo and stimulated anti-echo about the middle of k-space subsequent to ∼3 min of user interaction.There was no significant difference between measures obtained for FAST+CSPAMM and FAST+SPAMM for mean peak twist (13.5 ± 2.7° versus 11.9 ± 4.0°), torsion (3.4 ± 0.8°/cm versus 2.9 ± 1.0°/cm), twisting rate (76.8 ± 22.2°/s versus 68.2 ± 23.4°/s), untwisting rate (-102.7 ± 24.6°/s versus -106.6 ± 32.4°/s), normalized untwisting rate (-7.9 ± 2.2/s versus -9.9 ± 4.4/s), and time of peak twist (279 ± 23 ms versus 293 ± 25 ms) (all P > 0.01). FAST+CSPAMM also provided measures of duration of untwisting (148 ± 21 ms) and the ratio of rapid untwist to peak twist (0.8 ± 0.3). Bland-Altman analysis of FAST+CSPAMM and FAST+SPAMM twist data demonstrates excellent agreement with a bias of 1.1° and 95% confidence intervals of [-3.3°, 5.2°].FAST+CSPAMM is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist and torsion.

    View details for DOI 10.1002/jmri.23849

    View details for Web of Science ID 000315220000015

    View details for PubMedID 23371791

    View details for PubMedCentralID PMC3578174

  • Chemical shift-induced phase errors in phase-contrast MRI MAGNETIC RESONANCE IN MEDICINE Middione, M. J., Ennis, D. B. 2013; 69 (2): 391–401


    Phase-contrast magnetic resonance imaging is subject to numerous sources of error, which decrease clinical confidence in the reported measures. This work outlines how stationary perivascular fat can impart a significant chemical shift induced phase-contrast magnetic resonance imaging measurement error using computational simulations, in vitro, and in vivo experiments. This chemical shift error does not subtract in phase difference processing, but can be minimized with proper parameter selection. The chemical shift induced phase errors largely depend on both the receiver bandwidth and the TE. Both theory and an in vivo comparison of the maximum difference in net forward flow between vessels with and without perivascular fat indicated that the effects of chemically shifted perivascular fat are minimized by the use of high bandwidth (814 Hz/px) and an in-phase TE (high BW-TE(IN)). In healthy volunteers (N = 10) high BW-TE(IN) significantly improves intrapatient net forward flow agreement compared with low bandwidth (401 Hz/px) and a mid-phase TE as indicated by significantly decreased measurement biases and limits of agreement for the ascending aorta (1.8 ± 0.5 mL vs. 6.4 ± 2.8 mL, P = 0.01), main pulmonary artery (2.0 ± 0.9 mL vs. 11.9 ± 5.8 mL, P = 0.04), the left pulmonary artery (1.3 ± 0.9 mL vs. 5.4 ± 2.5 mL, P = 0.003), and all vessels (1.7 ± 0.8 mL vs. 7.2 ± 4.4 mL, P = 0.001).

    View details for DOI 10.1002/mrm.24262

    View details for Web of Science ID 000314059500011

    View details for PubMedID 22488490

    View details for PubMedCentralID PMC3396715

  • Variable flip angle balanced steady-state free precession for lower SAR or higher contrast cardiac cine imaging. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Srinivasan, S. n., Ennis, D. B. 2013


    PURPOSE: Cardiac cine balanced steady-state free precession (bSSFP) imaging uses a high flip angle (FA) to obtain high blood-myocardium signal-to-noise and contrast-to-noise ratios (CNR). Use of high FAs, however, results in substantially increased SAR. Our objective was to develop a variable FA bSSFP cardiac cine imaging technique with: (1) low SAR and blood-myocardium CNR similar to conventional constant FA bSSFP (CFA-bSSFP) or (2) increased blood-myocardium CNR compared to CFA-bSSFP with similar SAR. METHODS: Variable FA bSSFP cardiac cine imaging was achieved using an asynchronous k-space acquisition, which is asynchronous to the cardiac cycle (aVFA-bSSFP). Bloch simulations and phantom experiments were performed to compare the signal, resolution, and frequency response of the variable FA bSSFP and CFA-bSSFP schemes. Ten volunteers were imaged with different aVFA-bSSFP and asynchronous CFA-bSSFP schemes and compared to conventional segmented CFA-bSSFP. RESULTS: The SAR of aVFA-bSSFP is significantly decreased by 36% compared to asynchronous CFA-bSSFP (1.9 ± 0.2 vs. 3.0 ± 0.2 W/kg, P <  10(-10) ) for similar blood-myocardium CNR (34 ± 6 vs. 35 ± 9, P = 0.5). Alternately, the CNR of the aVFA-bSSFP is improved by 28% compared to asynchronous CFA-bSSFP (49 ± 9 vs. 38 ± 8, P <  10(-4) ) with similar SAR (3.2 ± 0.5 vs. 3.3 ± 0.5 W/kg, P = 0.6). CONCLUSION: aVFA-bSSFP can be used for lower SAR or higher contrast cardiac cine imaging compared to the conventional segmented CFA-bSSFP imaging. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24764

    View details for PubMedID 23629954

  • Multi-scale, multi-modal image integration for image-guided clinical interventions in the head and neck anatomy. Studies in health technology and informatics Santhanam, A. P., Dou, T., Neylon, J., Min, Y., Kupelian, A., Sheng, K., Ennis, D., Rolland, J., Low, D., Kupelian, P. 2013; 184: 380–86


    The aim of this paper is to enable model guided multi-scale and multi-modal image integration for the head and neck anatomy. The image modality used for this purpose includes multi-pose Magnetic Resonance Imaging (MRI), Mega Voltage CT, and hand-held Optical Coherence Tomography. A biomechanical model that incorporates subject-specific young's modulus and shear modulus properties is developed from multi-pose MRI, positioned in the treatment setup using Mega Voltage CT (MVCT), and actuated using multiple kinect surface cameras to mimic patient postures during Optical Coherence Microscopy (OCM) imaging. Two different 3D tracking mechanisms were employed for aligning the patient surface and the probe position to the MRI data. The results show the accuracy of the two tracking algorithms and the 3D head and neck deformation representing the multiple poses, the subject will take during the OCM imaging.

    View details for PubMedID 23400188

  • Injection of gadolinium contrast through pediatric central venous catheters: a safety study PEDIATRIC RADIOLOGY Moriarty, J. M., Kung, G. L., Ramos, Y., Moghaddam, A. N., Ennis, D. B., Finn, J. 2012; 42 (9): 1064–69


    Catheter rupture during CT angiography has prompted policies prohibiting the use of electronic injectors with peripherally inserted central venous catheters (PICCs) not only for CT but also for MRI. Consequently, many institutions mandate hand injection for MR angiography, limiting precision of infusion rates and durations of delivery.To determine whether electronic injection of gadolinium-based contrast media through a range of small-caliber, single-lumen PICCs would be safe without risk of catheter rupture over the range of clinical protocols and determine whether programmed flow rates and volumes were realized when using PICCs for contrast delivery.Experiments were performed and recorded using the Medrad Spectris Solaris EP MR Injection System. PICC sizes, contrast media and flow rates were based on common institutional protocols.No catheters were damaged during any experiments. Mean difference between programmed and delivered volume was 0.07 ± 0.10 mL for all experiments. Reduced flow rates and prolonged injection durations were observed when the injector's pressure-limiting algorithm was triggered, only in protocols outside the clinical range.PICCs commonly used in children can withstand in vitro power injection of gadolinium-based contrast media at protocols significantly above clinical levels.

    View details for DOI 10.1007/s00247-012-2397-z

    View details for Web of Science ID 000307717800004

    View details for PubMedID 22526282

  • The dependence of radiofrequency induced pacemaker lead tip heating on the electrical conductivity of the medium at the lead tip MAGNETIC RESONANCE IN MEDICINE Langman, D. A., Goldberg, I. B., Judy, J., Finn, J., Ennis, D. B. 2012; 68 (2): 606–13


    Radiofrequency induced pacemaker lead tip heating is one of the main reasons magnetic resonance imaging (MRI) is contraindicated for patients with pacemakers. The objective of this work was to evaluate the dependence of pacemaker lead tip heating during MRI scanning on the electrical conductivity of the medium surrounding the pacemaker lead tip. The effect of conductivity was measured using hydroxyethyl cellulose, polyacrylic acid, and saline with conductivities ranging from 0 to 3 S/m which spans the range of human tissue conductivity. The maximum lead tip heating observed in polyacrylic acid was 50.4 °C at 0.28 S/m, in hydroxyethyl cellulose the maximum was 36.8 °C at 0.52 S/m, and in saline the maximum was 12.5 °C at 0.51 S/m. The maximum power transfer theorem was used to calculate the relative power deposited in the solution based on the characteristic impedance of the pacemaker lead and test solution impedance. The results demonstrate a strong correlation between the relative power deposited and pacemaker lead tip heating for hydroxyethyl cellulose and saline solutions. Maximum power deposition occurred when the impedance of the solution matched the pacemaker lead impedance. Pacemaker lead tip heating is dependent upon the electrical conductivity of the solution at the lead tip and should be considered when planning in vitro gel or saline experiments.

    View details for DOI 10.1002/mrm.23235

    View details for Web of Science ID 000306318900034

    View details for PubMedID 22213610

  • Fourier analysis of STimulated echoes (FAST) for the quantitative analysis of left ventricular twist JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Natsuaki, Y., Ennis, D. B. 2012; 35 (3): 587–93


    To validate a novel method for the rapid and facile quantification of left ventricular (LV) twist from tagged magnetic resonance images and demonstrate the potential clinical utility in a series of 20 healthy volunteers.Cardiac magnetic resonance imaging (MRI) short-axis images were acquired with tissue tagging in 20 healthy subjects and six canines. The tagged images were processed using a novel Fourier Analysis of the STimulated echoes (FAST) method, which uses a series of Fourier-space operations to measure LV twist with limited user interaction. A subset of eight healthy subjects and the canine data were compared to results from previously validated "gold standard" software (FindTags). Interobserver and intraobserver coefficients of variation (CV(INTER) and CV(INTRA) ), linear regression, and Bland-Altman analyses were used to assess agreement between observers and methods.CV(INTRA) for peak systolic twist (2.9% and 2.6%) and CV(INTER) (4.3% and 4.2%) were all small. Linear regression analysis of the FAST and FindTags twist values indicated very good agreement in healthy subjects (R = 0.91) and in canines (R = 0.95). Bland-Altman comparison of the FAST and FindTags twist results indicated excellent agreement in healthy subjects (bias of -0.5°, 95% confidence intervals (-4.3°, 4.3°)) and canines (bias of 0.2°, 95% confidence intervals (-2.7°, 3.1°)). Peak systolic twist in healthy subjects averaged 10.5 ± 1.9° degrees.The FAST method for quantifying LV twist produces results that are not significantly different from the current "gold standard" in a fraction of the user interaction time and has demonstrated feasibility in human subjects.

    View details for DOI 10.1002/jmri.22863

    View details for Web of Science ID 000300690400012

    View details for PubMedID 22069227

    View details for PubMedCentralID PMC3288273

  • Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Itoh, A., Stephens, E. H., Ennis, D. B., Carlhall, C., Bothe, W., Nguyen, T. C., Swanson, J. C., Miller, D. C., Ingels, N. B. 2012; 302 (1): H180-H187


    Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.

    View details for DOI 10.1152/ajpheart.00687.2011

    View details for PubMedID 22037187

  • 3D Reconstruction and Image Fusion using Transurethral Ultrasound Natarajan, S., Culjat, M., Singh, R., Ennis, D., Marks, L., Grundfest, W. S., IEEE IEEE. 2012: 138–41
  • The Presence of Two Local Myocardial Sheet Populations Confirmed by Diffusion Tensor MRI and Histological Validation JOURNAL OF MAGNETIC RESONANCE IMAGING Kung, G. L., Tom C Nguyen, T. C., Itoh, A., Skare, S., Ingels, N. B., Miller, D. C., Ennis, D. B. 2011; 34 (5): 1080-1091


    To establish the correspondence between the two histologically observable and diffusion tensor MRI (DTMRI) measurements of myolaminae orientation for the first time and show that single myolaminar orientations observed in local histology may result from histological artifact.DTMRI was performed on six sheep left ventricles (LV), then corresponding direct histological transmural measurements were made within the anterobasal and lateral-equatorial LV. Secondary and tertiary eigenvectors of the diffusion tensor were compared with each of the two locally observable sheet orientations from histology. Diffusion tensor invariants were calculated to compare differences in microstructural diffusive properties between histological locations with one observable sheet population and two observable sheet populations.Mean difference ± 1SD between DTMRI and histology measured sheet angles was 8° ± 27°. Diffusion tensor invariants showed no significant differences between histological locations with one observable sheet population and locations with two observable sheet populations.DTMRI measurements of myolaminae orientations derived from the secondary and tertiary eigenvectors correspond to each of the two local myolaminae orientations observed in histology. Two local sheet populations may exist throughout LV myocardium, and one local sheet population observed in histology may be a result of preparation artifact.

    View details for DOI 10.1002/jmri.22725

    View details for Web of Science ID 000296206900011

    View details for PubMedID 21932362

    View details for PubMedCentralID PMC3195899

  • Pacemaker Lead Tip Heating in Abandoned and Pacemaker-Attached Leads at 1.5 Tesla MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Langman, D. A., Goldberg, I. B., Finn, J., Ennis, D. B. 2011; 33 (2): 426–31


    To assess the risk of RF-induced heating in pacemaker-attached and abandoned leads using in vitro temperature measurements at 1.5 Tesla as a function of lead length.Five custom lead lengths, 20-60 cm, were exposed to a uniform magnitude and phase radiofrequency electric field to examine the effect of lead length on pacemaker lead tip heating for pacemaker-attached and abandoned pacemaker leads.Abandoned and pacemaker-attached leads show resonant heating behavior and maximum heating occurs at different lead lengths due to the differences in termination conditions. For clinical lead lengths (40-60 cm) abandoned leads exhibited greater lead tip heating compared with pacemaker-attached leads.Current recommendations for MRI pacemaker safety should highlight the possible increased risk for patients with abandoned leads as compared to pacemaker-attached leads.

    View details for DOI 10.1002/jmri.22463

    View details for Web of Science ID 000286953300019

    View details for PubMedID 21274985

  • Analytical method to measure three-dimensional strain patterns in the left ventricle from single slice displacement data JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE Moghaddam, A., Saber, N. R., Wen, H., Finn, J., Ennis, D. B., Gharib, M. 2010; 12: 33


    Displacement encoded Cardiovascular MR (CMR) can provide high spatial resolution measurements of three-dimensional (3D) Lagrangian displacement. Spatial gradients of the Lagrangian displacement field are used to measure regional myocardial strain. In general, adjacent parallel slices are needed in order to calculate the spatial gradient in the through-slice direction. This necessitates the acquisition of additional data and prolongs the scan time. The goal of this study is to define an analytic solution that supports the reconstruction of the out-of-plane components of the Lagrangian strain tensor in addition to the in-plane components from a single-slice displacement CMR dataset with high spatio-temporal resolution. The technique assumes incompressibility of the myocardium as a physical constraint.The feasibility of the method is demonstrated in a healthy human subject and the results are compared to those of other studies. The proposed method was validated with simulated data and strain estimates from experimentally measured DENSE data, which were compared to the strain calculation from a conventional two-slice acquisition.This analytical method reduces the need to acquire data from adjacent slices when calculating regional Lagrangian strains and can effectively reduce the long scan time by a factor of two.

    View details for DOI 10.1186/1532-429X-12-33

    View details for Web of Science ID 000280092400001

    View details for PubMedID 20515489

    View details for PubMedCentralID PMC2903580

  • Cardiac Active Contraction Parameters Estimated from Magnetic Resonance Imaging Wang, V. Y., Lam, H. I., Ennis, D. B., Cowan, B. R., Young, A. A., Nash, M. P., Camara, O., Pop, M., Rhode, K., Sermesant, M., Smith, N., Young, A. SPRINGER-VERLAG BERLIN. 2010: 194-+
  • Mitral annular hinge motion contribution to changes in mitral septal-lateral dimension and annular area 88th Annual Meeting of the American-Association-for-Thoracic-Surgery Itoh, A., Ennis, D. B., Bothe, W., Swanson, J. C., Krishnamurthy, G., Nguyen, T. C., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2009: 1090–99


    The mitral annulus is a dynamic, saddle-shaped structure consisting of fibrous and muscular regions. Normal physiologic mechanisms of annular motion are incompletely understood, and more complete characterization is needed to provide rational basis for annuloplasty ring design and to enhance clinical outcomes.Seventeen sheep had radiopaque markers implanted; 16 around the annulus and 2 on middle anterior and posterior leaflet edges. Four-dimensional marker coordinates were acquired with biplanar videofluoroscopy at 60 Hz. Hinge angle was quantified between fibrous and muscular annular planes, with 0 degrees defined at end diastole, to characterize its contribution to alterations in mitral septal-lateral dimension and 2-dimensional total annular area throughout the cardiac cycle.During isovolumic contraction (pre-ejection), hinge angle abruptly increased, reaching maximum (steepest saddle shape, change 18 degrees +/- 13 degrees ) at peak left ventricular pressure. During ejection, hinge angle did not change; it then decreased during early filling (change 2 degrees +/- 2 degrees ). Septal-lateral dimension and total area paralleled hinge angle dynamics and leaflet distance (anterior to posterior marker). Pre-ejection septal-lateral reduction was 13% +/- 7% (3.3 +/- 1.5 mm) from 9% muscular dimension fall and 18 degrees +/- 13 degrees hinge angle increase.Pre-ejection increase in hinge angle contributes substantially to septal-lateral and total area reduction, facilitating leaflet coaptation. Semirigid annuloplasty rings or partial bands may preserve hinge motion, but possible recurrent annular dilatation could result in recurrent mitral regurgitation. Long-term clinical studies are required to determine who might benefit most from preserving intrinsic hinge motion without compromising repair durability.

    View details for DOI 10.1016/j.jtcvs.2009.03.067

    View details for PubMedID 19747697

  • Regional Mitral Leaflet Opening During Acute Ischemic Mitral Regurgitation 4th Biennial Meeting of the Society-for-Heart-Valve-Disease Bothe, W., Ennis, D. B., Carlhall, C. J., Nguyen, T. C., Timek, T. A., Lai, D. T., Itoh, A., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2009: 586–96


    Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics were quantified along the entire valvular coaptation line in an ovine model of acute IMR.Ten radiopaque markers were sutured in pairs on the anterior (A1-E1) and corresponding posterior (A2-E2) leaflet edges from the anterior (A1/A2) to the posterior (E1/E2) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings.Hemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 +/- 0.3 versus 2.3 +/- 0.7, p < 0.05), decreased contractility (dP/dt(max): 1,948 +/- 598 versus 1,119 +/- 293 mmHg/s, p < 0.05), and slower left ventricular relaxation rate (dP/dt(min): -1,079 +/- 188 versus -538 +/- 147 mmHg/s, p < 0.05). During ischemia, valve opening occurred earlier (A1/A2: 112 +/- 28 versus 83 +/- 43 ms, B1/B2: 105 +/- 32 versus 68 +/- 35 ms, C1/C2: 126 +/- 25 versus 74 +/- 37 ms, D1/D2: 114 +/- 28 versus 71 +/- 34 ms, E1/E2: 125 +/- 29 versus 105 +/- 33 ms; all p < 0.05) and was slower (A1/A2: 16.8 +/- 9.6 versus 14.2 +/- 9.4 cm/s, B1/B2: 40.4 +/- 9.9 versus 32.2 +/- 10.0 cm/s, C1/C2: 59.0 +/- 14.9 versus 50.4 +/- 18.1 cm/s, D1/D2: 34.4 +/- 10.4 versus 25.5 +/- 10.9 cm/s; all p < 0.05), except at the posterior edge (E1/E2: 13.3 +/- 8.7 versus 10.6 +/- 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia.Acute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.

    View details for PubMedID 20099707

  • Active stiffening of mitral valve leaflets in the beating heart AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Itoh, A., Krishnamurthy, G., Swanson, J. C., Ennis, D. B., Bothe, W., Kuhl, E., Karlsson, M., Davis, L. R., Miller, D. C., Ingels, N. B. 2009; 296 (6): H1766-H1773


    The anterior leaflet of the mitral valve (MV), viewed traditionally as a passive membrane, is shown to be a highly active structure in the beating heart. Two types of leaflet contractile activity are demonstrated: 1) a brief twitch at the beginning of each beat (reflecting contraction of myocytes in the leaflet in communication with and excited by left atrial muscle) that is relaxed by midsystole and whose contractile activity is eliminated with beta-receptor blockade and 2) sustained tone during isovolumic relaxation, insensitive to beta-blockade, but doubled by stimulation of the neurally rich region of aortic-mitral continuity. These findings raise the possibility that these leaflets are neurally controlled tissues, with potentially adaptive capabilities to meet the changing physiological demands on the heart. They also provide a basis for a permanent paradigm shift from one viewing the leaflets as passive flaps to one viewing them as active tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to MV disease, but even the definitions of MV disease itself.

    View details for DOI 10.1152/ajpheart.00120.2009

    View details for PubMedID 19363135

  • Reduced Systolic Torsion in Chronic "Pure" Mitral Regurgitation CIRCULATION-CARDIOVASCULAR IMAGING Ennis, D. B., Nguyen, T. C., Itoh, A., Bothe, W., Liang, D. H., Ingels, N. B., Miller, D. C. 2009; 2 (2): 85-92


    Global left ventricular (LV) torsion declines with chronic ischemic mitral regurgitation (MR), which may accelerate the LV remodeling spiral toward global cardiomyopathy; however, it has not been definitively established whether this torsional decline is attributable to the infarct, the MR, or their combined effect. We tested the hypothesis that chronic "pure" MR alone reduces global LV torsion.Chronic "pure" MR was created in 13 sheep by surgically punching a 3.5- to 4.8-mm hole (HOLE) in the mitral valve posterior leaflet. Nine control (CNTL) sheep were operated on concurrently. At 1 (WK-01) and 12 weeks (WK-12) postoperatively, the 4D motion of implanted radiopaque markers was used to calculate global LV torsion. MR-grade in HOLE was greater than CNTL at WK-01 and WK-12 (2.5+/-1.1 versus 0.6+/-0.5, P<0.001 at WK-12). HOLE LV mass index was larger at WK-12 compared with CNTL (195+/-14 versus 170+/-17 g/m(2), P<0.01), indicating LV remodeling. Global LV systolic torsion decreased in HOLE from WK-01 to WK-12 (4.1+/-2.8 degrees versus 1.7+/-1.7 degrees , P<0.01), but did not change in CNTL (5.5+/-1.8 degrees versus 4.2+/-2.7 degrees , P=NS). Global LV torsion was lower in HOLE relative to CNTL at WK-12 (P<0.05) but not at WK-01 (P=NS).Twelve weeks of chronic "pure" MR resulting in mild global LV remodeling is associated with significantly increased LV mass index and reduced global LV systolic torsion, but no other significant changes in hemodynamics. MR alone is a major component of torsional deterioration in "pure" MR and may be an important factor in chronic ischemic mitral regurgitation.

    View details for DOI 10.1161/CIRCIMAGING.108.785923

    View details for PubMedID 19808573

  • QUANTIFICATION OF IN VIVO STRESSES IN THE OVINE ANTERIOR MITRAL VALVE LEAFLET ASME Summer Bioengineering Conference Krishnamurthy, G., Ltoh, A., Bothe, W., Ennis, D. B., Swanson, J. C., Kuhl, E., Miller, D. C., Ingels, N. B. AMER SOC MECHANICAL ENGINEERS. 2009: 131–132
  • Myofiber angle distributions in the ovine left Ventricle do not conform to computationally optimized predictions JOURNAL OF BIOMECHANICS Ennis, D. B., Nguyen, T. C., Riboh, J. C., Wigstroem, L., Harrington, K. B., Daughters, G. T., Ingels, N. B., Miller, D. C. 2008; 41 (15): 3219-3224


    Recent computational models of optimized left ventricular (LV) myofiber geometry that minimize the spatial variance in sarcomere length, stress, and ATP consumption have predicted that a midwall myofiber angle of 20 degrees and transmural myofiber angle gradient of 140 degrees from epicardium to endocardium is a functionally optimal LV myofiber geometry. In order to test the extent to which actual fiber angle distributions conform to this prediction, we measured local myofiber angles at an average of nine transmural depths in each of 32 sites (4 short-axis levels, 8 circumferentially distributed blocks in each level) in five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral and anterolateral wall near the papillary muscles, and -9 degrees in all other regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with spatial heterogeneity (averaging a low of 51 degrees in the basal posterior sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We conclude that midwall myofiber angles and transmural myofiber angle gradients in the ovine heart are regionally non-uniform and differ significantly from the predictions of present-day computationally optimized LV myofiber models. Myofiber geometry in the ovine heart may differ from other species, but model assumptions also underlie the discrepancy between experimental and computational results. To test the predictive capability of the current computational model would we propose using an ovine specific LV geometry and comparing the computed myofiber orientations to those we report herein.

    View details for DOI 10.1016/j.jbiomech.2008.08.007

    View details for PubMedID 18805536

  • Alterations in transmural myocardial strain - An early marker of left ventricular dysfunction in mitral regurgitation? 80th Annual Scientific Session of the American-Heart-Association (AHA) Carlhaell, C. J., Nguyen, T. C., Itoh, A., Ennis, D. B., Bothe, W., Liang, D., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2008: S256–S262


    In asymptomatic patients with severe isolated mitral regurgitation (MR), identifying the onset of early left ventricular (LV) dysfunction can guide the timing of surgical intervention. We hypothesized that changes in LV transmural myocardial strain represent an early marker of LV dysfunction in an ovine chronic MR model.Sheep were randomized to control (CTRL, n=8) or experimental (EXP, n=12) groups. In EXP, a 3.5- or 4.8-mm hole was created in the posterior mitral leaflet to generate "pure" MR. Transmural beadsets were inserted into the lateral and anterior LV wall to radiographically measure 3-dimensional transmural strains during systole and diastolic filling, at 1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12 weeks (3.0 [2-4] versus 0.5 [0-2]; 3.0 [1-4] versus 0.5 [0-1], respectively, both P<0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201+/-18 versus 173+/-17 g/m(2); P<0.01). LVEDVI increased in EXP from 1 to 12 weeks (P=0.015). Between the 1 and 12 week values, the change in BNP (-4.5+/-4.4 versus -3.0+/-3.6 pmol/L), PRSW (9+/-13 versus 23+/-18 mm Hg), tau (-3+/-11 versus -4+/-7 ms), and systolic strains was similar between EXP and CTRL. The changes in longitudinal diastolic filling strains between 1 and 12 weeks, however, were greater in EXP versus CTRL in the subendocardium (lateral: -0.08+/-0.05 versus 0.02+/-0.14; anterior: -0.10+/-0.05 versus -0.02+/-0.07, both P<0.01).Twelve weeks of ovine "pure" MR caused LV remodeling with early changes in LV function detected by alterations in transmural myocardial strain, but not by changes in BNP, PRSW, or tau.

    View details for DOI 10.1161/CIRCULATIONAHA.107.753525

    View details for PubMedID 18824764

  • Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Krishnamurthy, G., Ennis, D. B., Itoh, A., Bothe, W., Swanson, J. C., Karlsson, M., Kuhl, E., Miller, D. C., Ingels, N. B. 2008; 295 (3): H1141-H1149


    We measured leaflet displacements and used inverse finite-element analysis to define, for the first time, the material properties of mitral valve (MV) leaflets in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four-dimensional coordinates were obtained from biplane videofluoroscopic marker images (60 frames/s) during three complete cardiac cycles. A finite-element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR; when the pressure difference across the valve is approximately 0), as the minimum stress reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The leaflet shear modulus (G(circ-rad)) and elastic moduli in both the commisure-commisure (E(circ)) and radial (E(rad)) directions were obtained using the method of feasible directions to minimize the difference between simulated and measured displacements. Group mean (+/-SD) values (17 animals, 3 heartbeats each, i.e., 51 cardiac cycles) were as follows: G(circ-rad) = 121 +/- 22 N/mm2, E(circ) = 43 +/- 18 N/mm2, and E(rad) = 11 +/- 3 N/mm2 (E(circ) > E(rad), P < 0.01). These values, much greater than those previously reported from in vitro studies, may result from activated neurally controlled contractile tissue within the leaflet that is inactive in excised tissues. This could have important implications, not only to our understanding of mitral valve physiology in the beating heart but for providing additional information to aid the development of more durable tissue-engineered bioprosthetic valves.

    View details for DOI 10.1152/ajpheart.00284.2008

    View details for PubMedID 18621858

  • The effect of pure mitral regurgitation on mitral annular geometry and three-dimensional saddle shape 87th Annual Meeting of the American-Association-for-Thoracic-Surgery Nguyen, T. C., Itoh, A., Carlhall, C. J., Bothe, W., Timek, T. A., Ennis, D. B., Oakes, R. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2008: 557–65


    Chronic ischemic mitral regurgitation is associated with mitral annular dilatation in the septal-lateral dimension and flattening of the annular 3-dimensional saddle shape. To examine whether these perturbations are caused by the ischemic insult, mitral regurgitation, or both, we investigated the effects of pure mitral regurgitation (low pressure volume overload) on annular geometry and shape.Eight radiopaque markers were sutured evenly around the mitral annulus in sheep randomized to control (CTRL, n = 8) or experimental (HOLE, n = 12) groups. In HOLE, a 3.5- to 4.8-mm hole was punched in the posterior leaflet to generate pure mitral regurgitation. Four-dimensional marker coordinates were obtained radiographically 1 and 12 weeks postoperatively. Mitral annular area, annular septal-lateral and commissure-commissure dimensions, and annular height were calculated every 16.7 ms.Mitral regurgitation grade was 0.4 +/- 0.4 in CTRL and 3.0 +/- 0.8 in HOLE (P < .001) at 12 weeks. End-diastolic left ventricular volume index was greater in HOLE at both 1 and 12 weeks; end-systolic volume index was larger in HOLE at 12 weeks. Mitral annular area increased in HOLE predominantly in the commissure-commissure dimension, with no difference in annular height between HOLE versus CTRL at 1 or 12 weeks, respectively.In contrast with annular septal-lateral dilatation and flattening of the annular saddle shape observed with chronic ischemic mitral regurgitation, pure mitral regurgitation was associated with commissure-commissure dimension annular dilatation and no change in annular shape. Thus, infarction is a more important determinant of septal-lateral dilatation and annular shape than mitral regurgitation, which reinforces the need for disease-specific designs of annuloplasty rings.

    View details for DOI 10.1016/j.jtcvs.2007.12.087

    View details for PubMedID 18805251

  • Non-uniform transmural remodeling in ovine chronic mitral regurgitation Ennis, D. B., Nguyen, T. C., Itoh, A., Carlhaell, C. J., Oakes, R. A., Bothe, W., Liang, D., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2008
  • Effects of acute ischemic mitral regurgitation on three-dimensional mitral leaflet edge geometry 21st Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS) Bothe, W., Nguyen, T. C., Ennis, D. B., Itoh, A., Carlhall, C. J., Lai, D. T., Ingels, N. B., Miller, D. C. OXFORD UNIV PRESS INC. 2008: 191–97


    Improved quantitative understanding of in vivo leaflet geometry in ischemic mitral regurgitation (IMR) is needed to improve reparative techniques, yet few data are available due to current imaging limitations. Using marker technology we tested the hypotheses that IMR (1) occurs chiefly during early systole; (2) affects primarily the valve region contiguous with the myocardial ischemic insult; and (3) results in systolic leaflet edge restriction.Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A(1)-E(1)) and posterior (A(2)-E(2)) mitral leaflet free edges from the anterior commissure (A(1)-A(2)) to the posterior commissure (E(1)-E(2)). Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D marker coordinates before and during acute proximal left circumflex artery occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant-MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was the distance of the midpoint of paired markers to the mitral annular plane at EndS.Acute ischemia increased echocardiographic MR grade (0.5+/-0.3 vs 2.3+/-0.7, p<0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7+/-10 vs 22+/-19 mm(2), 1+/-2 vs 18+/-16 mm(2), 0 vs 17+/-15 mm(2)); Mid-MOA (9+/-13 vs 25+/-17 mm(2), 3+/-6 vs 21+/-19 mm(2), 0 vs 25+/-17 mm(2)); and Post-MOA (8+/-10 vs 25+/-16, 2+/-4 vs 22+/-13 mm(2), 0 vs 23+/-13 mm(2)), all p<0.05. There was no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline conditions or ischemia. Tenting height increased with ischemia near the central and the anterior commissure leaflet edges (B(1)-B(2): 7.1+/-1.8mm vs 7.9+/-1.7 mm, C(1)-C(2): 6.9+/-1.3mm vs 8.0+/-1.5mm, both p<0.05).MOA during ischemia was larger throughout systole, indicating that acute IMR in this setting is a holosystolic phenomenon. Despite discrete postero-lateral myocardial ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was associated with leaflet restriction near the central and the anterior commissure leaflet edges. This entire constellation of annular, valvular, and subvalvular ischemic alterations should be considered in the approach to mitral repair for IMR.

    View details for DOI 10.1016/j.ejcts.2007.10.024

    View details for PubMedID 18321461

  • Diffusion tensor analysis with invariant gradients and rotation tangents IEEE TRANSACTIONS ON MEDICAL IMAGING Kindlmann, G., Ennis, D. B., Whitaker, R. T., Westin, C. 2007; 26 (11): 1483-1499


    Guided by empirically established connections between clinically important tissue properties and diffusion tensor parameters, we introduce a framework for decomposing variations in diffusion tensors into changes in shape and orientation. Tensor shape and orientation both have three degrees-of-freedom, spanned by invariant gradients and rotation tangents, respectively. As an initial demonstration of the framework, we create a tunable measure of tensor difference that can selectively respond to shape and orientation. Second, to analyze the spatial gradient in a tensor volume (a third-order tensor), our framework generates edge strength measures that can discriminate between different neuroanatomical boundaries, as well as creating a novel detector of white matter tracts that are adjacent yet distinctly oriented. Finally, we apply the framework to decompose the fourth-order diffusion covariance tensor into individual and aggregate measures of shape and orientation covariance, including a direct approximation for the variance of tensor invariants such as fractional anisotropy.

    View details for DOI 10.1109/TMI.2007.907277

    View details for Web of Science ID 000250897700008

    View details for PubMedID 18041264

  • Alterations in transmural myocardial strain: An early marker of left ventricular dysfunction in mitral regurgitation? 80th Annual Scientific Session of the American-Heart-Association (AHA) Nguyen, T. C., Carlhall, C. J., Itoh, A., Oakes, R. A., Ennis, D. B., Bothe, W., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2007: 368–68
  • Altered myocardial shear strains are associated with chronic ischemic mitral regurgitation 42nd Annual Meeting of the Society-of-Thoracic-Surgeons Nguyen, T. C., Cheng, A., Langer, F., Rodriguez, F., Oakes, R. A., Itoh, A., Ennis, D. B., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2007: 47–54


    Ischemic mitral regurgitation (IMR) limits life expectancy and can lead to postinfarction global left ventricular (LV) dilatation and remodeling, the pathogenesis of which is not completely known. We tested the hypothesis that IMR perturbs adjacent myocardial LV systolic strains.Thirteen sheep had three columns of miniature beads inserted across the lateral LV wall, with additional epicardial markers silhouetting the ventricle. One week later posterolateral infarction was created. Seven weeks thereafter, the animals were divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative histology were used to calculate ventricular volumes, transmural myocardial systolic strains, and systolic fiber shortening.Seven weeks after infarction, end-diastolic (ED) volume increased similarly in both groups, end-systolic (ES) E13 (circumferential-radial) shear increased in both groups, but more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12 (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs -0.01, p < 0.005). There were no significant differences in ED or ES remodeling strains or systolic fiber shortening between IMR(-) and IMR(+).An equivalent increase in LV end-diastolic (ED) volume in both groups, coupled with unchanged ED and end-systolic remodeling strains as well as systolic circumferential, longitudinal, and radial strains, argue against a global LV or regional myocardial geometric basis for the cardiomyopathy associated with IMR. Further, similar systolic fiber shortening in both groups militates against an intracellular (cardiomyocyte) mechanism. The differences in subepicardial E12 and E13 shears, however, suggest a causal role of altered interfiber (cytoskeleton and extracellular-matrix) interactions.

    View details for DOI 10.1016/j.athoracsur.2006.08.039

    View details for PubMedID 17184629

  • Dobutamine myocardial strain rate response is transmurally inhomogeneous 79th Annual Scientific Session of the American-Heart-Association Itoh, A., Nguyen, T. C., Cheng, A., Oakes, R. A., Ennis, D. B., Kameda, Y., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: 570–70
  • Detection of myocardial capillary orientation with intravascular iron-oxide nanoparticles in spin-echo MRI MAGNETIC RESONANCE IN MEDICINE Vignaud, A., Rodriguez, Ennis, D. B., DeSilva, R., Kellman, P., Taylor, J., Bennett, E., Wen, H. 2006; 55 (4): 725–30


    In mammalian hearts the capillaries are closely aligned with the muscle fibers. We report our observation of a main-field direction-dependent contrast in MR spin-echo (SE) images of the heart in the presence of Ferumoxtran-10, an intravascular iron-oxide nanoparticle contrast agent (CA). We describe a novel MRI method for mapping the preferential orientation of capillaries in the myocardial wall. The eigenvector corresponding to the minimum eigen value of the R2 relaxation rate tensor is consistent with the expected orientation of the capillary network. Preliminary results also demonstrate the feasibility of this method for in vivo application to rodent imaging.

    View details for DOI 10.1002/mrm.20827

    View details for Web of Science ID 000236602700003

    View details for PubMedID 16506158

    View details for PubMedCentralID PMC2881601

  • The visible heart - Analysis of myocardial fiber structure using three-dimensional histology Experimental Biology 2006 Annual Meeting Wigstrom, L., Ennis, D. B., Nguyen, T. C., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1198–A1198
  • Regional heterogeneity of myofiber orientation in the ovine left ventricle Nquyen, T. C., Ennis, D. B., Riboh, J. C., Harrington, K. B., Wigstrom, L., Daughter, G. T., Miller, C. D., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1195
  • Noninvasive measurement of myocardial tissue volume change during systolic contraction and diastolic relaxation in the canine left ventricle MAGNETIC RESONANCE IN MEDICINE Rodriguez, Ennis, D. B., Wen, H. 2006; 55 (3): 484–90


    In coronary circulation the flow in epicardial arteries and veins is observed to be pulsatile and out of phase with each other. Theoretical considerations predict that this phenomenon extends to all levels of the vascular tree and leads to a cyclic fluctuation of regional tissue volume. Intramyocardial tissue volume change between end-systole and end-diastole was measured noninvasively with MRI in 10 closed-chest beagles. The displacement encoding with stimulated-echo technique was used to obtain pixel-by-pixel tissue displacement field between end-diastole and end-systole and vice versa in the midlevel left ventricle, from which the 3D strain matrix and volume changes were calculated. The volume change was between 0.8+/-0.5% (mean+/-STD) in the epicardial layer and 1.5+/-0.6% in the subendocardial layer of the left ventricle. Tissue volume fluctuation reflects the amount of arterial inflow in a heartbeat under the assumption that regional arterial inflow and venous outflow have little time overlap. The corresponding perfusion level was estimated to be from (1.0+/-0.6) ml/min/g in the epicardial layer to (1.7+/-0.6) ml/min/g in the subendocardial layer, in good agreement with microsphere measurements in the same dog model. The result supports the notion of high arterial resistance at the microvascular level from intramyocardial pressure during systole.

    View details for DOI 10.1002/mrm.20786

    View details for Web of Science ID 000235858400004

    View details for PubMedID 16408273

    View details for PubMedCentralID PMC2887312

  • Transmural left ventricular shear strain alterations adjacent to and remote from infarcted myocardium JOURNAL OF HEART VALVE DISEASE Cheng, A., Langer, F., Nguyen, T. C., Malinowski, M., Ennis, D. B., Daughters, G. T., Ingels, N. B., Miller, D. C. 2006; 15 (2): 209-218


    In some patients, dysfunction in a localized infarct region spreads throughout the left ventricle to aggravate mitral regurgitation and produce deleterious global left ventricular (LV) remodeling. Alterations in transmural strains could be a trigger for this process, as these changes can produce apoptosis and extracellular matrix disruption. The hypothesis was tested that localized infarction perturbs transmural strain patterns not only in adjacent regions but also at remote sites.Transmural radiopaque beadsets were inserted surgically into the anterior basal and lateral equatorial LV walls of 25 sheep; additional markers were used to silhouette the left ventricle. One week thereafter, 10 sheep had posterior wall infarction from (obtuse marginal occlusion, INFARCT) and 15 had no infarction (SHAM). Four-dimensional marker dynamics were studied with biplane videofluoroscopy eight weeks later. Fractional area shrinkage, LV volumes and transmural circumferential, longitudinal and radial systolic strains were analyzed.Compared to SHAM, INFARCT greatly increased longitudinal-radial shear (mid-wall: 0.07 +/- 0.07 versus 0.14 +/- 0.06; subendocardium: 0.03 +/- 0.07 versus 0.20 +/- 0.08) in the inner half of the lateral LV wall and increased circumferential-radial shear (mid-wall: 0.03 +/- 0.05 versus 0.10 +/- 0.04; subepicardium: 0.02 +/- 0.05 versus 0.12 +/- 0.10) increased in the outer half of the LATERAL wall. In the ANTERIOR wall, INFARCT also increased longitudinal-radial shear (midwall: 0.01 +/- 0.05 versus 0.12 +/- 0.04; subendocardium: 0.04 +/- 0.09 versus 0.25 +/- 0.20) in the inner layers.Increased transmural shear strains were found not only in an adjacent region, but also at a site remote from a localized infarction. This perturbation could trigger remodeling processes that promote the progression of ischemic cardiomyopathy. A better understanding of this process is important for the future development of surgical therapies to reverse destructive LV remodeling.

    View details for PubMedID 16607903

  • Evidence of structural remodeling in the dyssynchronous failing heart CIRCULATION RESEARCH Helm, P. A., Younes, L., Beg, M. F., Ennis, D. B., Leclercq, C., Faris, O. P., McVeigh, E., Kass, D., Miller, M. I., Winslow, R. L. 2006; 98 (1): 125–32


    Ventricular remodeling of both geometry and fiber structure is a prominent feature of several cardiac pathologies. Advances in MRI and analytical methods now make it possible to measure changes of cardiac geometry, fiber, and sheet orientation at high spatial resolution. In this report, we use diffusion tensor imaging to measure the geometry, fiber, and sheet architecture of eight normal and five dyssynchronous failing canine hearts, which were explanted and fixed in an unloaded state. We apply novel computational methods to identify statistically significant changes of cardiac anatomic structure in the failing and control heart populations. The results demonstrate significant regional differences in geometric remodeling in the dyssynchronous failing heart versus control. Ventricular chamber dilatation and reduction in wall thickness in septal and some posterior and anterior regions are observed. Primary fiber orientation showed no significant change. However, this result coupled with the local wall thinning in the septum implies an altered transmural fiber gradient. Further, we observe that orientation of laminar sheets become more vertical in the early-activated septum, with no significant change of sheet orientation in the late-activated lateral wall. Measured changes in both fiber gradient and sheet structure will affect both the heterogeneity of passive myocardial properties as well as electrical activation of the ventricles.

    View details for PubMedID 16339482

  • Orthogonal tensor invariants and the analysis of diffusion tensor magnetic resonance images MAGNETIC RESONANCE IN MEDICINE Ennis, D. B., Kindlmann, G. 2006; 55 (1): 136–46


    This paper outlines the mathematical development and application of two analytically orthogonal tensor invariants sets. Diffusion tensors can be mathematically decomposed into shape and orientation information, determined by the eigenvalues and eigenvectors, respectively. The developments herein orthogonally decompose the tensor shape using a set of three orthogonal invariants that characterize the magnitude of isotropy, the magnitude of anisotropy, and the mode of anisotropy. The mode of anisotropy is useful for resolving whether a region of anisotropy is linear anisotropic, orthotropic, or planar anisotropic. Both tensor trace and fractional anisotropy are members of an orthogonal invariant set, but they do not belong to the same set. It is proven that tensor trace and fractional anisotropy are not mutually orthogonal measures of the diffusive process. The results are applied to the analysis and visualization of diffusion tensor magnetic resonance images of the brain in a healthy volunteer. The theoretical developments provide a method for generating scalar maps of the diffusion tensor data, including novel fractional anisotropy maps that are color encoded for the mode of anisotropy and directionally encoded colormaps of only linearly anisotropic structures, rather than of high fractional anisotropy structures.

    View details for PubMedID 16342267

  • Visualization of tensor fields using superquadric glyphs MAGNETIC RESONANCE IN MEDICINE Ennis, D. B., Kindlman, G., Rodriguez, Helm, P. A., McVeigh, E. R. 2005; 53 (1): 169–76


    The spatially varying tensor fields that arise in magnetic resonance imaging are difficult to visualize due to the multivariate nature of the data. To improve the understanding of myocardial structure and function a family of objects called glyphs, derived from superquadric parametric functions, are used to create informative and intuitive visualizations of the tensor fields. The superquadric glyphs are used to visualize both diffusion and strain tensors obtained in canine myocardium. The eigensystem of each tensor defines the glyph shape and orientation. Superquadric functions provide a continuum of shapes across four distinct eigensystems (lambda(i), sorted eigenvalues), lambda(1) = lambda(2) = lambda(3) (spherical), lambda(1) < lambda(2) = lambda(3) (oblate), lambda(1) > lambda(2) = lambda(3) (prolate), and lambda(1) > lambda(2) > lambda(3) (cuboid). The superquadric glyphs are especially useful for identifying regions of anisotropic structure and function. Diffusion tensor renderings exhibit fiber angle trends and orthotropy (three distinct eigenvalues). Visualization of strain tensors with superquadric glyphs compactly exhibits radial thickening gradients, circumferential and longitudinal shortening, and torsion combined. The orthotropic nature of many biologic tissues and their DTMRI and strain data require visualization strategies that clearly exhibit the anisotropy of the data if it is to be interpreted properly. Superquadric glyphs improve the ability to distinguish fiber orientation and tissue orthotropy compared to ellipsoids.

    View details for DOI 10.1002/mrm.20318

    View details for Web of Science ID 000226380700023

    View details for PubMedID 15690516

    View details for PubMedCentralID PMC2169197

  • 3D breath-held cardiac function with projection reconstruction in steady state free precession validated using 2D cine MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Peters, D. C., Ennis, D. B., Rohatgi, P., Syed, M. A., McVeigh, E. R., Arai, A. E. 2004; 20 (3): 411–16


    To develop and validate a three-dimensional (3D) single breath-hold, projection reconstruction (PR), balanced steady state free precession (SSFP) method for cardiac function evaluation against a two-dimensional (2D) multislice Fourier (Cartesian) transform (FT) SSFP method.The 3D PR SSFP sequence used projections in the x-y plane and partitions in z, providing 70-80 msec temporal resolution and 1.7 x 1.7 x 8-10 mm in a 24-heartbeat breath hold. A total of 10 volunteers were imaged with both methods, and the measurements of global cardiac function were compared.Mean signal-to-noise ratios (SNRs) for the blood and myocardium were 114 and 42 (2D) and 59 and 21 (3D). Bland-Altman analysis comparing the 2D and 3D ejection fraction (EF), left ventricular end diastolic volume (LVEDV) and end systolic volume (LVESV), and end diastolic myocardial mass (LVEDM) provided values of bias +/-2 SD of 0.6% +/- 7.7 % for LVEF, 5.9 mL +/- 20 mL for LVEDV, -2.8 mL +/- 12 mL for LVESV, and -0.61 g +/- 13 g for LVEDM. 3D interobserver variability was greater than 2D for LVEDM and LVESV.In a single breath hold, the 3D PR method provides comparable information to the standard 2D FT method, which employs 10-12 breath holds.

    View details for DOI 10.1002/jmri.20145

    View details for Web of Science ID 000223522200009

    View details for PubMedID 15332248

    View details for PubMedCentralID PMC2396304

  • Endocardial versus epicardial electrical synchrony during LV free-wall pacing AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Faris, O. P., Evans, F. J., Dick, A. J., Raman, V. K., Ennis, D. B., Kass, D. A., McVeigh, E. R. 2003; 285 (5): H1864–H1870


    Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony (fusion with intrinsic conduction) is important. To better understand this disparity, we simultaneously mapped both endocardial and epicardial electrical activation during LV free-wall pacing at varying atrioventricular delays (AV delay 0-150 ms) in six normal dogs with the use of a 64-electrode LV endocardial basket and a 128-electrode epicardial sock. The transition from dyssynchronous LV-paced activation to synchronous RA-paced activation was studied by constructing activation time maps for both endo- and epicardial surfaces as a function of increasing AV delay. The AV delay at the transition from dyssynchronous to synchronous activation was defined as the transition delay (AVt). AVt was variable among experiments, in the range of 44-93 ms on the epicardium and 47-105 ms on the endocardium. Differences in endo- and epicardial AVt were smaller (-17 to +12 ms) and not significant on average (-5.0 +/- 5.2 ms). In no instance was the transition to synchrony complete on one surface without substantial concurrent transition on the other surface. We conclude that both epicardial and endocardial synchrony due to fusion of native with ventricular stimulation occur nearly concurrently. Assessment of electrical epicardial delay, as often used clinically during cardiac resynchronization therapy lead placement, should provide adequate assessment of stimulation delay for inner wall layers as well.

    View details for DOI 10.1152/ajpheart.00282.2003

    View details for Web of Science ID 000185951800008

    View details for PubMedID 12855422

    View details for PubMedCentralID PMC2396262

  • Assessment of regional systolic and diastolic dysfunction in familial hypertrophic cardiomyopathy using MR tagging MAGNETIC RESONANCE IN MEDICINE Ennis, D. B., Epstein, F. H., Kellman, P., Fananapazir, L., McVeigh, E. R., Arai, A. E. 2003; 50 (3): 638–42


    Diastolic and systolic left ventricular (LV) dysfunction often significantly contribute to disabling symptoms in familial hypertrophic cardiomyopathy (FHC). This study compares regional LV function (midwall circumferential strain) during systole and diastole in eight FHC patients and six normal volunteers (NVs) using MR tagging. A prospectively-gated fast gradient-echo sequence with an echo-train readout was modified to support complementary spatial modulation of magnetization (CSPAMM) tagging and full cardiac cycle data acquisition using the cardiac phase to order reconstruction (CAPTOR), thus providing tag persistence and data acquisition during the entire cardiac cycle. Total systolic strains in FHC patients were significantly reduced in septal and inferior regions (both P < 0.01). Early-diastolic strain rates were reduced in all regions of the FHC group (all P < 0.03). The combination of CSPAMM and CAPTOR allows regional indices of myocardial function to be quantified throughout the cardiac cycle. This technique reveals regional differences in systolic and diastolic impairment in FHC patients.

    View details for PubMedID 12939774

  • High-resolution MRI of cardiac function with projection reconstruction and steady-state free precession MAGNETIC RESONANCE IN MEDICINE Peters, D. C., Ennis, D. B., McVeigh, E. R. 2002; 48 (1): 82–88


    The purpose of this study was to investigate the trabecular structure of the endocardial wall of the living human heart, and the effect of that structure on the measurement of myocardial function using MRI. High-resolution MR images (0.8 x 0.8 x 8 mm voxels) of cardiac function were obtained in five volunteers using a combination of undersampled projection reconstruction (PR) and steady-state free precession (SSFP) contrast in ECG-gated breath-held scans. These images provide movies of cardiac function with new levels of endocardial detail. The trabecular-papillary muscle complex, consisting of a mixture of blood and endocardial structures, is measured to constitute as much as 50% of the myocardial wall in some sectors. Myocardial wall strain measurements derived from tagged MR images show correlation between regions of trabeculae and papillary muscles and regions of high strain, leading to an overestimation of function in the lateral wall.

    View details for DOI 10.1002/mrm.10193

    View details for Web of Science ID 000176648900010

    View details for PubMedID 12111934

    View details for PubMedCentralID PMC2396263

  • Measurement of F-actin mechanics with laser tracking microrheology: Role of particle surface chemistry. McGrath, J. L., Ennis, D. B., Kuo, S. C. AMER SOC CELL BIOLOGY. 1999: 21A
  • Time resolved displacement-based registration of in vivo cDTI cardiomyocyte orientations Verzhbinsky, I. A., Magrath , P., Aliotta, E., Moulin, K., Ennis, D. B., Perotti , L. E. 2018