Abstract
Background Cardiotoxicity is a major limiting factor preventing dose-effective use of multiple cytotoxic agents in cancer treatment. Current cardiotoxicity diagnosis is based on functional changes that occur late in the course of the disease. In this pre-clinical pilot study, we hypothesize myocardial T1 and T2 mapping will identify mice at risk of death secondary to doxorubicin-induced cardiotoxicity prior to cardiac function deterioration. Methods Eleven healthy, 10-week-old C57BL/6 female mice were included in the study. All procedures are in accordance with an Institutional Animal Care and Use Committee approved protocol. Doxorubicin-induced cardiotoxicity was generated by giving 8 mg/kg of doxorubicin via intraperitoneal (IP) injection weekly for 4 weeks in n = 8 randomly selected mice. A control group of n = 3 mice was given a weekly volume equivalent dose of IP normal saline. Each mouse underwent ECG-gated CMR on a 7T small animal scanner (ClinScan, Bruker, Billerica, MA) prior to treatment, at 2 weeks, and post-treatment. Steady-state free precession images were acquired at the left ventricular base, mid-ventricle, and apex and ejection fraction (EF) was calculated (Figure 1). Gadopentetate Dimeglumine contrast was injected via the tail vein at a dose of 1 mL/kg. Myocardial T1 and T2 maps were generated using dedicated offline software to calculate the pixel-wise relaxation
Highlights
Cardiotoxicity is a major limiting factor preventing dose-effective use of multiple cytotoxic agents in cancer treatment
Steady-state free precession images were acquired at the left ventricular base, mid-ventricle, and apex and ejection fraction (EF) was calculated (Figure 1)
Average myocardial T1 and T2 relaxation times and ejection fraction were compared between mice that died during treatment, survived to the end of treatment, and controls using repeated measure linear modeling
Summary
Cardiotoxicity is a major limiting factor preventing dose-effective use of multiple cytotoxic agents in cancer treatment. Current cardiotoxicity diagnosis is based on functional changes that occur late in the course of the disease. In this pre-clinical pilot study, we hypothesize myocardial T1 and T2 mapping will identify mice at risk of death secondary to doxorubicin-induced cardiotoxicity prior to cardiac function deterioration
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