Abstract

Doxorubicin is an effective, commonly used chemotherapeutic drug. However, this drug is accompanied with disadvantages. Specifically, doxorubicin is associated with cardiotoxicity, characterized by left ventricle dysfunction. We hypothesize that 4D ultrasound imaging can reveal cardiac changes associated with doxorubicin-induced cardiotoxicity earlier in disease progression than 2D ultrasound imaging. To test this hypothesis, C57BL/6J mice were separated into treatment or control groups. Intraperitoneal injections were administered weekly for 4 weeks, each dosage equivalent to 4 mg/kg of either doxorubicin (treated) or saline (control). A Vevo3100 high frequency ultrasound system (FUJIFILM VisualSonics) was used to collect 2D and 4D ultrasound images of cardiac structures. Weekly imaging was carried out for 8 weeks following baseline imaging. 2D images were analyzed using Vevo Lab (VisualSonics) software. Parameters reflecting diastolic and systolic function including ejection fraction were collected, as well as left ventricle dimensions. Ejection fraction, or the percent of blood volume expelled from the left ventricle, is a commonly-used marker of cardiotoxicity. The 4D ultrasound images, analyzed using a custom-built MATLAB Graphical User Interface, uniquely quantified cardiac strain using the full volume of the heart. Cardiac strain is a measure of cardiac wall displacement. In mice treated with doxorubicin, decreases in both ejection fraction and strain are anticipated. Ongoing image analysis will quantify any changes in cardiac strain that may occur prior to changes in the metrics found using 2D analysis. The ability to identify dysfunction using cardiac strain before traditional analysis has potential to improve early diagnosis and treatment of cardiotoxicity.

Keywords

Cardiotoxicity, Doxorubicin, Ultrasound

Date of this Version

2025

Download

Share

COinS