Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model

Ibrahim, El Sayed H.; Baruah, Dhiraj; Croisille, Pierre; Stojanovska, Jadranka; Rubenstein, Jason; Frei, Anne; Schlaak, Rachel A.; Lin, Chieh Yu; Pipke, Jamie L.; Lemke, Angela; Xu, Zhiqiang; Klaas, Amanda; Brehler, Michael; Flister, Michael J.; LaViolette, Peter S.; Gore, Elizabeth; Bergom, Carmen

doi:10.1016/j.jaccao.2020.12.006

Cited by 16 publications

(19 citation statements)

References 29 publications

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“…Small animal TTE platforms may be utilized to assess LVEF, ventricular wall motion abnormalities, valvular disease, and other pathologies in rodent RIHD studies ( 172 ), while clinical ultrasound machines are sufficient for larger animal studies. Cardiac MRI using high-resolution small animal MRI scanners offer similar endpoints as TTE for use in studies of RIHD ( 173 ). Similarly, Tc-99m-Sestamibi SPECT has been utilized to detect perfusion deficits in studies of RIHD ( 47 ) and myocardial infarction ( 174 ).…”

Section: Detection Methods For Rihd/rimf and Biomarkersmentioning

confidence: 99%

Preclinical models of radiation-induced cardiac toxicity: Potential mechanisms and biomarkers

Dreyfuss

Velalopoulou²,

Avgousti³

et al. 2022

Front. Oncol.

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Radiation therapy (RT) is an important modality in cancer treatment with >50% of cancer patients undergoing RT for curative or palliative intent. In patients with breast, lung, and esophageal cancer, as well as mediastinal malignancies, incidental RT dose to heart or vascular structures has been linked to the development of Radiation-Induced Heart Disease (RIHD) which manifests as ischemic heart disease, cardiomyopathy, cardiac dysfunction, and heart failure. Despite the remarkable progress in the delivery of radiotherapy treatment, off-target cardiac toxicities are unavoidable. One of the best-studied pathological consequences of incidental exposure of the heart to RT is collagen deposition and fibrosis, leading to the development of radiation-induced myocardial fibrosis (RIMF). However, the pathogenesis of RIMF is still largely unknown. Moreover, there are no available clinical approaches to reverse RIMF once it occurs and it continues to impair the quality of life of long-term cancer survivors. Hence, there is an increasing need for more clinically relevant preclinical models to elucidate the molecular and cellular mechanisms involved in the development of RIMF. This review offers an insight into the existing preclinical models to study RIHD and the suggested mechanisms of RIMF, as well as available multi-modality treatments and outcomes. Moreover, we summarize the valuable detection methods of RIHD/RIMF, and the clinical use of sensitive radiographic and circulating biomarkers.

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Section: Detection Methods For Rihd/rimf and Biomarkersmentioning

confidence: 99%

Preclinical models of radiation-induced cardiac toxicity: Potential mechanisms and biomarkers

Dreyfuss

Velalopoulou²,

Avgousti³

et al. 2022

Front. Oncol.

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“…Rats that received 24 Gy radiation, whole-heart radiation were compared to sham-treated rats. They concluded that MRI regional myocardial strain is sensitive imaging diagnostic for detecting RT-induced subclinical cardiac damage before global cardiac function was compromised [86].…”

Section: Radiation Therapy-induced Cardiotoxicitymentioning

confidence: 99%

Experimental Model of Cardiotoxicity

Erbaş¹,

Altuntaş²,

Çağlar³

et al. 2022

Risk Factors for Cardiovascular Disease

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The occurrence of heart electrophysiology dysfunction or/and muscle damage is referred to as cardiotoxicity. The heart weakens and becomes less efficient at pumping and hence circulating blood. Cardiomyopathy can be caused by a variety of factors, including viral infections, diseases such as diabetes, ischemia, hypertension, obesity, radiation therapy, antipsychotic drugs, cytotoxic drugs, most notably chemotherapeutic agents; antitumor antibiotics, monoclonal antibodies, tyrosine kinase inhibitors, platinum-based compounds, microtubule inhibitors, vinca alkaloids, antimetabolites, proteasome inhibitors, topoisomerase inhibitors, alkylating agents, corticosteroids. This chapter focuses on the mechanisms of cardiotoxicity, animal models and transgenic methods used in studies, and the effects of therapeutic agents on cardiotoxicity.

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“…Experiments using ErbB2-deficient conditional mutant mice demonstated cardiomyopathy related to trastuzumab (79). ErbB2 signaling in cardiomyocytes was found to be essential to prevent dilated cardiomyopathy (73). Zebrafish model was also use to predict sorafenib cardiotoxicity (80).…”

Section: Preclinical Animal Modelsmentioning

confidence: 99%