Table 3.
Summary of cardiotoxicity animal model studies employing CMR imaging
Ref. # | Species | Anti-cancer agent and administration route | Chemotherapy dose and frequency | MRI field strength | CMR tissue findings | Histopathology findings |
---|---|---|---|---|---|---|
Large animals | ||||||
Galan-Arriola et al. [8] | Pig | Dox, ICA | 0.45mg/kg 2× weekly for 3–5 weeks | 3.0 T | Increased T2 that preceded T1 increase and LVEF decrease | Cardiomyocyte vacuolization and interstitial fibrosis |
Hong et al. [21] | Rabbit | Dox, IV | 1.0 mg/kg 2× weekly for16 weeks | 3.0 T | Increase native T1 & ECV | Interstitial fibrosis, loss of myofibrils, & cardiomyocyte intracellular vacuolization |
Psaltis et al. [22] | Sheep | Dox, ICA | 1mg/kg twice weekly | - | Increased LGE | Increased fibrosis |
Meléndez et al. [24] | Monkey | Dox, IV | 30 to 60 mg/m2 biweekly up to 240 mg/m2 | 3.0 T | LVEF decline, increased LV mass index, ECV fraction, T2 | Increased LV collagen deposition; fibrosis, cardiomyocyte cross-section area. Decrease in the number of cardiomyocytes. |
Small animals | ||||||
Farhad et al. [25] | Mouse | Dox, SubQ pellet | 5 mg/kg/wk for 5 weeks | 9.4T | Increase ECV; T2 prolongation | Interstitial myocardial fibrosis and cardiac water |
Lightfoot et al. [28] | Rat | Dox, IV | 1.5 to 2.5 mg/kg/wk for 10 weeks | 1.5T | Increase in gadolinium enhancement | Cardiomyocyte vacuolization and degeneration, inflammatory cell infiltration, edema, diffuse myocardial fibrosis |
Cove-Smith et al. [29] | Rat | Dox, IV | 1.25 mg/kg for 8 weeks | 4.7T | Decreased LVEF, Increased peak and LGE | Cardiomyocyte degeneration, extensive vacuolation & myocardial fibrosis |
Dox: Doxorubicin; ICA: Intracoronary administration; IV: intravenous; SubQ: subcutaneous; T: Tesla; LVEF: left ventricular ejection fraction; ECV: extracellular volume; LGE: late gadolinium enhancement.