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Cardiovascular Engineering

Cardiovascular Engineering - Poster Session E

S17 - 4D Echocardiographic Assessment of Regional Strain in a Murine Model of Doxorubicin-Induced Cardiotoxicity

Saturday, October 11, 2025
10:00 AM - 11:00 AM PDT
Location: Exhibit Hall F, G & H

Introduction: : Cardiotoxicity remains a major clinical issue afflicting survivors of cancer globally. Systemic chemotherapy continues to be the standard of care for many cancers; however, cardiotoxicity resulting from off-target side effects of chemotherapeutic agents, specifically doxorubicin (DOX), remains a significant and persistent concern [1]. DOX is linked to cardiac dysfunction in 3-7% of patients’ post-cancer treatments who have received a cumulative dosage of 400 mg/m2 or more [1]. While two-dimensional (2D) echocardiography is the current standard in diagnosing cardiomyopathy, its reliance on geometric assumptions and limitations in measurement prevents robust regional cardiac assessment [2]. Therefore, we aim to characterize regional left ventricular (LV) strain using non-invasive four-dimensional ultrasound (4DUS) as a potentially more sensitive indicator of cardiac dysfunction in a murine model of DOX-induced cardiotoxicity.

Materials and

Methods: : C57BL/6J mice were assigned to an acute study (7-day duration; n=10 male). 25 mg/kg bodyweight DOX was injected intraperitoneally (n=7 for baseline and day 2, n=2 for day 7). All control mice (n = 3 acute) received equivalent volumes of saline at the same time points. Echocardiography was performed on all mice before the first injection using a Vevo3100 ultrasound system (FUJIFILM VisualSonics Inc.). The animals were then imaged at 2- and 7-days post-injection. A dobutamine stress test (4.5 ug/g bodyweight) was conducted at all non-baseline time points to assess cardiac performance under duress. Both 2D long-axis and 4D (3D volume over time) images were acquired to evaluate cardiac structure and function, shown in Figure 1. Ejection fraction (EF) was measured from 2D images using the VevoLAB software, and 4D images were analyzed with a custom MATLAB Graphical User Interface, quantifying global and regional LV strain.

Results, Conclusions, and Discussions:: EF from 2D shows no significant difference between DOX and control animals for all timepoints; however, EF nearly significantly (p=0.07) decreases for DOX animals from Day 2 to Day 7 (Figure 2A). The dobutamine (DB)-attributed increase in EF is lower for DOX-treated mice at both Day 2 and 7, although neither difference is significant. (Figure 2B). While also not significant, global longitudinal strain (GLS) in Figure 3A exhibits a smaller increase in magnitude due to dobutamine in DOX animals compared to Controls at Day 7. Global circumferential strain (GCS) in Figure 3B displays no significant difference between conditions at Day 2, but at Day 7, the significant increase in strain magnitude Controls due to dobutamine (p=0.02) is absent for DOX-treated animals.

Acute study findings hint at the loss of strain magnitude increase due to DB injection in DOX animals at Day 7, potentially suggesting that differences in longitudinal and circumferential strain magnitude increase after dobutamine injection could detect cardiac dysfunction due to acute cardiotoxic damage that 2D EF and non-DB strain cannot. Repeating this study with additional animals could help confirm or deny these conclusions, especially whether DB-induced EF or strain changes can detect cardiac dysfunction earlier. In general, small sample size and variations in ultrasound acquisition and analysis could explain data variation in the acute study. Completion of chronic study image acquisition and analysis will also illuminate whether damage caused by chronic mechanisms at more clinically similar dosages and schedules will be revealed earlier by 4D strain metrics as compared to 2D echocardiography.

Acknowledgements and/or References (Optional): : Acknowledgements: This work was partially supported by an American Heart Association Institutional Award for Undergraduate Student Training to Purdue University (23IAUST1032828)

References:

[1] Podyacheva, E. Y., Kushnareva, E. A., Karpov, A. A., & Toropova, Y. G. (2021). Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View from the Perspective of the Pathophysiologist and the Clinician. Frontiers in Pharmacology, 12, 670479. https://doi.org/10.3389/fphar.2021.670479

[2] Fox, A. G., Buonodono, K. E., Jones, A. R., Thomas, M., Schepers, L. E., Earl, C. C., Goergen, C. J., & Crouch, A. C. (2025). Multimodal Study of Murine Cardiovascular Remodeling: Four-Dimensional Ultrasound and Mass Spectrometry Imaging. Journal of Visualized Experiments, 215, 67347. https://doi.org/10.3791/67347