Quantification of murine myocardial infarct size using 2-D and 4-D high-frequency ultrasound

Dann, Melissa M.; Clark, Sydney Q.; Trzaskalski, Natasha A.; Earl, Conner C.; Schepers, Luke E; Pulente, Serena M.; Lennord, Ebonee N.; Annamalai, Karthik; Gruber, Joseph M.; Cox, Abigail; Lorenzen‐Schmidt, Ilka; Seymour, Richard J.; Kim, Kyoung-Han; Goergen, Craig J.; Mulvihill, Erin E.

doi:10.1152/ajpheart.00476.2021

Cited by 12 publications

(15 citation statements)

References 26 publications

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“…We conducted the strain analysis using a 4D Strain Toolbox. This custom software enables the visualization and quantification of 4DUS data to produce a 3D strain map over an entire cardiac cycle 48,49 . We first oriented the 4D images and centered them to PLAX, SAX, and coronal views of the left ventricle.…”

Section: Methodsmentioning

confidence: 99%

“…We manually adjusted the contours over the cardiac cycle using four SAX planes and three PLAX planes. Next, the software created a 4D mesh of the contours from which measurements of global cardiac function (e.g., ejection fraction, stroke volume) and regional function (strain, volume) can be extracted 48,49 . Custom toolbox cardiac wall motion with border tracings can be visualized in Video S1.…”

Section: Methodsmentioning

confidence: 99%

“…This custom software enables the visualization and quantification of 4DUS data to produce a 3D strain map over an entire cardiac cycle. 48,49 We first oriented the 4D images and centered them to PLAX, SAX, and coronal views of the left ventricle. Endocardial boundaries were set at peak systole and diastole for the apex and base.…”

Section: Four-dimensional Ultrasound Data Strain Analysismentioning

confidence: 99%

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Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart–brain dysfunctions in adulthood

et al. 2023

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Aim Retrospective studies suggest that mild traumatic brain injury (mTBI) in pediatric patients may lead to an increased risk of cardiac events. However, the exact functional and temporal dynamics and the associations between heart and brain pathophysiological trajectories are not understood. Methods A single impact to the left somatosensory cortical area of the intact skull was performed on juvenile mice (17 days postnatal). Cerebral 3D photoacoustic imaging was used to measure the oxygen saturation (sO2) in the impacted area 4 h after mTBI followed by 2D and 4D echocardiography at days 7, 30, 90, and 190 post‐impact. At 8 months, we performed a dobutamine stress test to evaluate cardiac function. Lastly, behavioral analyses were conducted 1 year after initial injury. Results We report a rapid and transient decrease in cerebrovascular sO2 and increased hemoglobin in the impacted left brain cortex. Cardiac analyses showed long‐term diastolic dysfunction and a diminished systolic strain response under stress in the mTBI group. At the molecular level, cardiac T‐p38MAPK and troponin I expression was pathologic modified post‐mTBI. We found linear correlations between brain sO2 measured immediately post‐mTBI and long‐term cardiac strain after 8 months. We report that initial cerebrovascular hypoxia and chronic cardiac dysfunction correlated with long‐term behavioral changes hinting at anxiety‐like and memory maladaptation. Conclusion Experimental juvenile mTBI induces time‐dependent cardiac dysfunction that corresponds to the initial neurovascular sO2 dip and is associated with long‐term behavioral modifications. These imaging biomarkers of the heart–brain axis could be applied to improve clinical pediatric mTBI management.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Four-dimensional Ultrasound Data Strain Analysismentioning

confidence: 99%

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Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart–brain dysfunctions in adulthood

et al. 2023

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“…In ischemia, there is altered LV shortening and elevated S strain, with no apparent change in RV strain. Dann et al 7 compared murine strain magnitudes after LV ischemia and reported significant reductions in LV free-wall shortening within the first seven days post ligation. Clinically, myocardial strain imaging is gaining traction as an indicator of heart function.…”

Section: Simulated Ischemiamentioning

confidence: 99%

Biventricular interaction during acute left ventricular ischemia in mice: a combined in-vivo and in-silico approach

Colebank

Taylor

Hacker

et al. 2023

Preprint

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Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure-volume loop data (n=3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure-volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia.

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“…Over the past few years, we have developed methods for high-sensitivity spatiotemporal mapping of 4D (3D + time) gated cardiac echocardiographic data [23][24][25][26]. These advances have allowed us to identify subtle imaging biomarkers in a variety of cardiac disease animal models of myocardial infarction [27,28], aortic aneurysm [29,30], and atherosclerosis [31]. Applying these techniques to 3D + time cardiovascular magnetic resonance (CMR) images offers a promising method for biomechanical characterization of pathologic changes in DMD patients.…”

Section: Introductionmentioning

confidence: 99%

Localized strain characterization of cardiomyopathy in Duchenne muscular dystrophy using novel 4D kinematic analysis of cine cardiovascular magnetic resonance

Earl

Pyle

Clark

et al. 2023

Journal of Cardiovascular Magnetic Resonance

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Background Cardiomyopathy (CMP) is the most common cause of mortality in Duchenne muscular dystrophy (DMD), though the age of onset and clinical progression vary. We applied a novel 4D (3D + time) strain analysis method using cine cardiovascular magnetic resonance (CMR) imaging data to determine if localized strain metrics derived from 4D image analysis would be sensitive and specific for characterizing DMD CMP. Methods We analyzed short-axis cine CMR image stacks from 43 DMD patients (median age: 12.23 yrs [10.6–16.5]; [interquartile range]) and 25 male healthy controls (median age: 16.2 yrs [13.3–20.7]). A subset of 25 male DMD patients age-matched to the controls (median age: 15.7 yrs [14.0-17.8]) was used for comparative metrics. CMR images were compiled into 4D sequences for feature-tracking strain analysis using custom-built software. Unpaired t-test and receiver operator characteristic area under the curve (AUC) analysis were used to determine statistical significance. Spearman’s rho was used to determine correlation. Results DMD patients had a range of CMP severity: 15 (35% of total) had left ventricular ejection fraction (LVEF) > 55% with no findings of myocardial late gadolinium enhancement (LGE), 15 (35%) had findings of LGE with LVEF > 55% and 13 (30%) had LGE with LVEF < 55%. The magnitude of the peak basal circumferential strain, basal radial strain, and basal surface area strain were all significantly decreased in DMD patients relative to healthy controls (p < 0.001) with AUC values of 0.80, 0.89, and 0.84 respectively for peak strain and 0.96, 0.91, and 0.98 respectively for systolic strain rate. Peak basal radial strain, basal radial systolic strain rate, and basal circumferential systolic strain rate magnitude values were also significantly decreased in mild CMP (No LGE, LVEF > 55%) compared to a healthy control group (p < 0.001 for all). Surface area strain significantly correlated with LVEF and extracellular volume (ECV) respectively in the basal (rho = − 0.45, 0.40), mid (rho = − 0.46, 0.46), and apical (rho = − 0.42, 0.47) regions. Conclusion Strain analysis of 3D cine CMR images in DMD CMP patients generates localized kinematic parameters that strongly differentiate disease from control and correlate with LVEF and ECV.

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Quantification of murine myocardial infarct size using 2-D and 4-D high-frequency ultrasound

Cited by 12 publications

References 26 publications

Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart–brain dysfunctions in adulthood

Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart–brain dysfunctions in adulthood

Biventricular interaction during acute left ventricular ischemia in mice: a combined in-vivo and in-silico approach

Localized strain characterization of cardiomyopathy in Duchenne muscular dystrophy using novel 4D kinematic analysis of cine cardiovascular magnetic resonance

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