Publications

Daniel Bruce Ennis
Professor of Radiology (Veterans Affairs) and, by courtesy, of Bioengineering

Bio

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.

Publications

  • Comprehensive Analysis of Relative Pressure Estimation Methods Utilizing 4D Flow MRI. ArXiv Hardy, B., Zimmermann, J., Lechner, V., Bonini, M., Sotelo, J. A., Burris, N. S., Ennis, D. B., Marlevi, D., Nordsletten, D. A. 2025

    Abstract

    4D flow MRI allows for the estimation of three-dimensional relative pressure fields, providing rich pressure information, unlike catheterization and Doppler echocardiography, which provide one-dimensional pressure drops only. The accuracy of one-dimensional pressure drops derived from 4D flow has been explored in previous literature, but additional work must be done to evaluate the accuracy of three-dimensional relative pressure fields. This work presents an analysis of three state-of-the-art relative pressure estimators: virtual Work-Energy Relative Pressure (vWERP), the Pressure Poisson Estimator (PPE), and the Stokes Estimator (STE). Spatiotemporal behavior and sensitivity to noise were determined in silico. Estimators were validated with a type B aortic dissection (TBAD) flow phantom with varying tear geometry and an array of twelve catheter pressure measurements. Finally, the performance of each estimator was evaluated across eight patient cases. In silico pressure field errors were lower in STE compared to PPE, although PPE pressures were less affected by noise. High velocity gradients and low spatial resolution contributed most significantly to local variations in 3D error fields. Low temporal resolution leads to highly transient peak pressure events being averaged, systematically underestimating peak pressures. In the flow phantom analysis, vWERP was the most accurate method, followed by STE and PPE. Each pressure estimator strongly correlated with ground truth pressure values despite the tendency to underestimate peak pressures. Patient case results demonstrated that the pressure estimators could be feasibly integrated into a clinical workflow.

    View details for PubMedID 40093359

    View details for PubMedCentralID PMC11908371

  • DENSE-SIM: A modular pipeline for the evaluation of cine DENSE images with sub-voxel ground-truth strain. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Barbaroux, H., Loecher, M., Brackenier, Y., Kunze, K. P., Neji, R., Pennell, D. J., Ennis, D. B., Nielles-Vallespin, S., Scott, A. D., Young, A. A. 2025: 101866

    Abstract

    Myocardial strain is a valuable biomarker for diagnosing and predicting cardiac conditions, offering additional prognostic information to traditional metrics like ejection fraction. While cardiovascular magnetic resonance (CMR) methods, particularly cine displacement encoding with stimulated echoes (DENSE), are the gold standard for strain estimation, evaluation of regional strain estimation requires precise ground truth. This study introduces DENSE-Sim, an open-source simulation pipeline for generating realistic cine DENSE images with high-resolution known ground truth strain, enabling evaluation of accuracy and precision in strain analysis pipelines.This pipeline is a modular tool designed for simulating cine DENSE images and evaluating strain estimation performance. It comprises four main modules: 1) anatomy generation, for creating end-diastolic cardiac shapes; 2) motion generation, to produce myocardial deformations over time and Lagrangian strain; 3) DENSE image generation, using Bloch equation simulations with realistic noise, spiral sampling, and phase-cycling; and 4) strain evaluation. To illustrate the pipeline, a synthetic dataset of 180 short-axis slices was created, and analysed using the commonly-used DENSEanalysis tool. The impact of the spatial regularization parameter (k) in DENSEanalysis was evaluated against the ground-truth pixel strain, to particularly assess the resulting bias and variance characteristics.Simulated strain profiles were generated with a myocardial SNR ranging from 3.9 to 17.7. For end-systolic radial strain, DENSEanalysis average signed error (ASE) in Green strain ranged from 0.04 ± 0.09 (true-calculated, mean ± std) for a typical regularization (k=0.9), to  - 0.01 ± 0.21 at low regularization (k=0.1). Circumferential strain ASE ranged from  - 0.00 ± 0.04 at k=0.9 to  - 0.01 ± 0.10 at k=0.1. This demonstrates that the circumferential strain closely matched the ground truth, while radial strain displayed more significant underestimations, particularly near the endocardium. A lower regularization parameter from 0.3 to 0.6 depending on the myocardial SNR, would be more appropriate to estimate the radial strain, as a compromise between noise compensation and global strain accuracy.Generating realistic cine DENSE images with high-resolution ground-truth strain and myocardial segmentation enables accurate evaluation of strain analysis tools, while reproducing key in vivo acquisition features, and will facilitate the future development of deep-learning models for myocardial strain analysis, enhancing clinical CMR workflows.

    View details for DOI 10.1016/j.jocmr.2025.101866

    View details for PubMedID 39988298

  • Characterizing variability in passive myocardial stiffness in healthy human left ventricles using personalized MRI and finite element modeling. Scientific reports Kolawole, F. O., Wang, V. Y., Freytag, B., Loecher, M., Cork, T. E., Nash, M. P., Kuhl, E., Ennis, D. B. 2025; 15 (1): 5556

    Abstract

    Abnormal passive stiffness of the heart muscle (myocardium) is evident in the pathophysiology of several cardiovascular diseases, making it an important indicator of heart health. Recent advancements in cardiac imaging and biophysical modeling now enable more effective evaluation of this biomarker. Estimating passive myocardial stiffness can be accomplished through an MRI-based approach that requires comprehensive subject-specific input data. This includes the gross cardiac geometry (e.g. from conventional cine imaging), regional diastolic kinematics (e.g. from tagged MRI), microstructural configuration (e.g. from diffusion tensor imaging), and ventricular diastolic pressure, whether invasively measured or non-invasively estimated. Despite the progress in cardiac biomechanics simulations, developing a framework to integrate multiphase and multimodal cardiac MRI data for estimating passive myocardial stiffness has remained a challenge. Moreover, the sensitivity of estimated passive myocardial stiffness to input data has not been fully explored. This study aims to: (1) develop a framework for integrating subject-specific in vivo MRI data into in silico left ventricular finite element models to estimate passive myocardial stiffness, (2) apply the framework to estimate the passive myocardial stiffness of multiple healthy subjects under assumed filling pressure, and (3) assess the sensitivity of these estimates to loading conditions and myofiber orientations. This work contributes toward the establishment of a range of reference values for material parameters of passive myocardium in healthy human subjects. Notably, in this study, beat-to-beat variation in left ventricular end-diastolic pressure was found to have a greater influence on passive myocardial material parameter estimation than variation in fiber orientation.

    View details for DOI 10.1038/s41598-025-89243-2

    View details for PubMedID 39953070

    View details for PubMedCentralID PMC11829060

  • An axis-specific mitral annuloplasty ring eliminates mitral regurgitation allowing mitral annular motion in an ovine model. Communications medicine Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Cork, T. E., Yajima, S., Wilkerson, R. J., Tran, N. A., Marin-Cuartas, M., Mullis, D. M., Baker, S. W., Tada, Y., Ueyama, T., Leipzig, M., Wang, V. Y., Ethiraj, S., Madira, S., Anilkumar, S., Walsh, S. K., Lucian, H. J., Huynh, C., Morris, K., Kim, O. S., Mulligan, J., Wang, H., Shudo, Y., Ennis, D. B., Woo, Y. J. 2025; 5 (1): 40

    Abstract

    Current mitral annuloplasty rings fail to restrict the anteroposterior distance while allowing dynamic mitral annular changes. We designed and manufactured a mitral annuloplasty ring that demonstrated axis-specific, selective flexibility to meet this clinical need. The objectives were to evaluate ex vivo biomechanics of this ring and to validate the annular dynamics and safety after ring implantation in vivo.Healthy human mitral annuli (n = 3) were tracked, and motions were isolated. Using the imaging data, we designed and manufactured our axis-specific mitral annuloplasty ring. An ex vivo annular dilation model was used to compare hemodynamics and chordal forces after repair using the axis-specific, rigid, and flexible rings in five porcine mitral valves. In vivo, axis-specific (n = 6), rigid (n = 6), or flexible rings (n = 6) were implanted into male Dorset sheep for annular motion analyses. Five additional animals receiving axis-specific rings survived for up to 6 months.Here we show the axis-specific, rigid, and flexible rings reduced regurgitation fraction to 4.7 ± 2.7%, 2.4 ± 3.2%, and 17.8 ± 10.0%, respectively. The axis-specific ring demonstrated lower average forces compared to the rigid ring (p = 0.046). Five animals receiving axis-specific rings survived for up to 6 months, with mitral annular motion preserved in vivo. Mature neoendocardial tissue coverage over the device was found to be complete with full endothelialization in all animals.The axis-specific mitral annuloplasty ring we designed demonstrates excellent capability to repair mitral regurgitation while facilitating dynamic mitral annular motion. This ring has tremendous potential for clinical translatability, representing a promising surgical solution for mitral regurgitation.

    View details for DOI 10.1038/s43856-025-00753-6

    View details for PubMedID 39939395

    View details for PubMedCentralID 3071018

  • Left Ventricular Twist and Circumferential Strain from MRI Tagging Predict Early Cardiovascular Disease in Duchenne Muscular Dystrophy. Diagnostics (Basel, Switzerland) Liu, Z. Q., Magrath, P., Maforo, N. G., Loecher, M., Wu, H. H., Prosper, A., Renella, P., Halnon, N., Ennis, D. B. 2025; 15 (3)

    Abstract

    Background/Objectives: Duchenne Muscular Dystrophy (DMD) is a prevalent fatal genetic disorder, and heart failure is the leading cause of mortality. Peak left ventricular (LV) circumferential strain (Ecc), twist, and circumferential-longitudinal shear angle (θCL) are promising biomarkers for the improved and early diagnosis of incipient heart failure. Our goals were as follows: 1) to characterize a spectrum of functional and rotational LV biomarkers in boys with DMD compared with healthy age-matched controls; and 2) to identify LV biomarkers of early cardiomyopathy in the absence of abnormal LVEF or LGE. Methods: Boys with DMD (N = 43) and age-matched healthy volunteers (N = 16) were prospectively enrolled and underwent a 3T CMR exam after obtaining informed consent. Breath-held MRI tagging was used to estimate left ventricular Ecc at the mid-ventricular level as well as the twist, torsion, and θCL between basal and apical LV short-axis slices. A two-tailed t-test with unequal variance was used to test group-wise differences. Multiple comparisons were performed with Holm-Sidak post hoc correction. Multiple-regression analysis was used to test for correlations among biomarkers. A binomial logistic regression model assessed each biomarker's ability to distinguish the following: (1) healthy volunteers vs. DMD patients, (2) healthy volunteers vs. LGE(-) DMD patients, and (3) LGE(-) DMD patients vs. LGE(+) DMD patients. Results: There was a significant impairment in the peak mid-wall Ecc [-17.0 ± 4.2% vs. -19.5 ± 1.9%, p < 7.8 × 10-3], peak LV twist (10.4 ± 4.3° vs. 15.6 ± 3.1°, p < 8.1 × 10-4), and peak LV torsion (2.03 ± 0.82°/mm vs. 2.8 ± 0.5°/mm, p < 2.6 × 10-3) of LGE(-) DMD patients when compared to healthy volunteers. There was a further significant reduction in the Ecc, twist, torsion, and θCL for LGE(+) DMD patients when compared to LGE(-) DMD patients. In the LGE(+) DMD patients, age significantly correlated with LVEF (r2 = 0.42, p = 9 × 10-3), peak mid-wall Ecc (r2 = 0.27, p = 0.046), peak LV Twist (r2 = 0.24, p = 0.06), peak LV torsion (r2 = 0.28, p = 0.04), and peak LV θCL (r2 = 0.23, p = 0.07). In the LGE(-) DMD patients, only the peak mid-wall Ecc was significantly correlated with age (r2 = 0.25, p = 0.006). The peak LV twist outperformed the peak mid-wall LV Ecc and EF in distinguishing DMD patients from healthy volunteer groups (AUC = 0.88, 0.80, and 0.72), as well as in distinguishing LGE(-) DMD patients from healthy volunteers (AUC = 0.83, 0.74, and 0.62). The peak LV twist and peak mid-wall LV Ecc performed similarly in distinguishing the LGE(-) and LGE(+) DMD cohorts (AUC = 0.74, 0.77, and 0.79). Conclusions: The peak mid-wall LV Ecc, peak LV twist, peak LV torsion, and peak LV θCL were significantly impaired in advance of the decreased LVEF and the development of focal myocardial fibrosis in boys with DMD and therefore were apparent prior to significant irreversible injury.

    View details for DOI 10.3390/diagnostics15030326

    View details for PubMedID 39941255