Aasish
Chowdary Karuturi

Dobutamine Stress Testing in 4D Strain Detection of Early Cardiotoxicity in a DOX-Treated Mouse Model STEM

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Aasish Chowdary Karuturi

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Doxorubicin (DOX) is a widely used chemotherapy drug, but its clinical use is limited by cardiotoxic effects that can lead to heart failure. Approximately 6% of patients develop clinical heart failure, and up to 18% experience subclinical dysfunction. This project tracks cardiac function and strain over time after DOX treatment in male C57BL/6J mice, focusing on dobutamine stress test as a way to detect latent cardiac damage that conventional echocardiography fails to characterize. Animals were administered 4 doses of 4 mg/kg body weight DOX weekly for X weeks; control animals were administered an equivalent volume of 0.9% saline.2D and 4D echocardiographic images were collected at baseline and 8 weekly time points afterwards using a Vevo 3100 ultrasound system from FUJIFILM Visualsonics. Metrics like ejection fraction, cardiac output, and chamber dimensions were measured using VevoLAB software. A custom MATLAB-based GUI developed in the Cardiovascular Imaging Research Laboratory was used to extract global and regional cardiac strain values from the 4D datasets. We performed dobutamine stress testing to evaluate whether strain changes become more pronounced under increased cardiac workload, expecting that changes in regional strain after dobutamine injection will reveal cardiac dysfunction before any non-dobutamine metrics. If confirmed, this would suggest that 4D strain imaging combined with stress testing is a more sensitive method for identifying cardiac dysfunction due to DOX. This could improve preclinical screening for cardiotoxicity in drug development studies as well as have potential clinical diagnostic applications. Keywords: Doxorubicin; Cardiotoxicity; 4D Strain Imaging; Dobutamine Stress Test; Echocardiography

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Purdue University / 2025

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Aasish Chowdary Karuturi

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