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Current in vivo abdominal aortic aneurysm (AAA) imaging approaches tend to focus on maximum diameter but do not measure three-dimensional (3D) vascular deformation or strain. Complex vessel geometries, heterogeneous wall compositions, and surrounding structures can all influence aortic strain. Improved understanding of complex aortic kinematics has the potential to increase our ability to predict aneurysm expansion and eventual rupture. Here, we describe a method that combines four-dimensional (4D) ultrasound and direct deformation estimation to compute in vivo 3D Green-Lagrange strain in murine angiotensin II-induced suprarenal dissecting aortic aneurysms, a commonly used small animal model. We compared heterogeneous patterns of the maximum, first-component 3D Green-Lagrange strain with vessel composition from mice with varying AAA morphologies. Intramural thrombus and focal breakage in the medial elastin significantly reduced aortic strain. Interestingly, a dissection that was not detected with high-frequency ultrasound also experienced reduced strain, suggesting medial elastin breakage that was later confirmed via histology. These results suggest that in vivo measurements of 3D strain can provide improved insight into aneurysm disease progression. While further work is needed with both preclinical animal models and human imaging studies, this initial murine study indicates that vessel strain should be considered when developing an improved metric for predicting aneurysm growth and rupture. [DOI: 10.1115/1.4043075]

Representative day 28 long-axis ultrasound images (top), 3D surface strains (middle), and bullseye strain maps (bottom) of the remodeled LVs for all five mice in the I/R group. The akinetic myocardium is marked in dashed yellow lines, and the strain estimated infarct size is outlined in solid black line. Sternal artifact is shaded in gray with black dashed border. Scalebar: 1mm.

Representative day 28 long-axis ultrasound images (top), 3D surface strains (middle), and bullseye strain maps (bottom) of the remodeled LVs for all five mice in the PL group. The akinetic myocardium is marked in dashed yellow lines, the strain estimated infarct boundary is outlined in solid black line, and the wall-thinned infarct boundary is marked in dotted white line. Sternal artifact is shaded in gray with black dashed border. Scalebar: 1mm.

Coronary artery disease remains the leading cause of death in the United States with over 1 million acute coronary events predicted to take place in 2019 alone. Heart failure, a common and deadly sequela of myocardial infarction (MI), is attributed to adverse ventricular remodeling driven by cardiomyocyte death, inflammation, and mechanical factors. Despite strong evidence suggesting the importance of myocardial mechanics in driving cardiac remodeling, many in vivo MI studies still rely on 2D analyses to estimate global left ventricular (LV) function and approximate strain using a linear definition. These metrics, while valuable in evaluating the overall impact of ischemic injury on cardiac health, do not capture regional differences in myocardial contractility. The objective of this work is therefore to expand upon existing ultrasound studies by enabling regional analysis of 3D myocardial strain. By integrating our recently developed four-dimensional ultrasound (4DUS) imaging technique with a direct deformation estimation algorithm for 3D strain, we identified unique remodeling patterns and regional strain differences between two murine models of MI with different infarct severities. By constructing 3D strain maps of the remodeling LVs, we were able to capture strain heterogeneity and characterize a sigmoidal strain profile at infarct border zones. Finally, we demonstrated that the maximum principal component of the 3D Green-Lagrange strain tensor correlates with LV remodeling severity and is predictive of final infarct size. Taken together, the presented work provides a novel and thorough approach to quantify regional 3D strain, an important component when assessing post-MI remodeling.

Representative day-28 maximum principal 3D strains are presented along the entire thickness of the LV wall for each surgical group. Yellow and blue regions correspond to areas of high and low strains respectively. A: anterior, S: septal, L: lateral; B: base. Scalebar: 1mm.

Bullseye maps of the maximum principal 3D Green-Lagrange strain (EI) for all 15 mice at baseline. Consistent high strain values throughout the LV myocardium across all animals highlight the reproducibility of the 3D strain technique.

Representative day 28 long-axis ultrasound images (top), 3D surface strains (middle), and bullseye strain maps (bottom) of the remodeled LVs for all five mice in the I/R group. The akinetic myocardium is marked in dashed yellow lines, and the strain estimated infarct size is outlined in solid black line. Sternal artifact is shaded in gray with black dashed border. Scalebar: 1mm.

Representative day-28 maximum principal 3D strains are presented along the entire thickness of the LV wall for each surgical group. Yellow and blue regions correspond to areas of high and low strains respectively. A: anterior, S: septal, L: lateral; B: base. Scalebar: 1mm.

Supplemental Material, DS1_TPX_10.1177_0192623319838491 for Epithelial–mesenchymal Transition Phenotypes in Vertebral Metastases of Lung Cancer by Alexandra M. Dieterly, Gozde Uzunalli, Chinyere M. Kemet, Arvin H. Soepriatna, Craig J. Goergen and L. Tiffany Lyle in Toxicologic Pathology

Bullseye maps of the maximum principal 3D Green-Lagrange strain (EI) for all 15 mice at baseline. Consistent high strain values throughout the LV myocardium across all animals highlight the reproducibility of the 3D strain technique.

Comparison of maximum principal strains estimated with 3D Direct Deformation Estimation (DDE, solid lines) and Vic2D (dashed lines). Short-axis ultrasound strain data along the anterior (red) and posterior (blue) myocardial walls are shown at baseline and at day 28 post-permanent ligation. Although both 3D-DDE and Vic2D demonstrated significantly lower strain values along the infarcted, anterior myocardium post-surgery, the 3D-DDE method more appropriately tracked changes in myocardial strain, as strain values returned to 0 at the end of the cardiac cycle.

Heart failure is a leading cause of death in the United States, and cardiac thrombus, a common morbidity associated with heart failure, significantly increases a patient’s risk of embolic events. The objective of this project is to characterize left-ventricular (LV) thrombus development using high frequency ultrasound imaging in a murine model. C57BL/6J wild-type mice (n=6) were injected intraperitoneally with iron dextran five times a week for six weeks to increase oxidative stress in the heart. Granulocyte-colony stimulating factor (G-CSF) was subcutaneously injected daily during the second week to initiate stem cell migration and stimulate endothelial cell activation, thus increasing the hypercoagulability state of the blood. A high-frequency, small animal ultrasound system (Vevo2100, VisualSonics FUJIFILM Inc.) and a 40 MHz central frequency transducer were used to track LV thrombus progression and evaluate LV function weekly. Four out of six mice developed thrombus, but no significant differences in LV performance were observed when compared to mice that did not form a thrombus. Further investigation is necessary to study the role of attenuated heart function on thrombus formation. Future work will incorporate a murine model of myocardial infarction to investigate if a severely compromised heart increases the risk of or accelerates LV thrombus formation. This study will aid in identifying patients who are predisposed to thrombus formation following a heart attack, leading to more effective prevention and treatment methods.