Magnetic resonance imaging of the regenerating neonatal mouse heart

Abstract

We present longitudinal magnetic resonance imaging (MRI) of neonatal mouse hearts during the first three weeks following coronary artery ligation to mimic heart attack. We confirm heart regeneration in individual animals injured on post-natal day 1 (P1) while those injured on P7 show the adult response of fibrosis, scarring and impaired heart performance. We document heart growth and development of the principal functional cardiac parameters, and also remodeling during tissue regeneration as compared to fibrosis when imaging repeatedly up to 21 days after myocardial infarction (MI). We reveal compensatory changes in cardiac function with the restoration of tissue and resolution of injury for the P1 cohort and sustained injury responses for the P7 cohort. This study resolves the controversy surrounding neonatal mouse heart regeneration and establishes a functional platform for live capture of the regenerative process and for the future testing of genetic or therapeutic interventions.

A Refined Protocol for Coronary Artery Ligation in the Neonatal Mouse

“…Adaptation of magnetic resonance imaging (MRI) to the neonatal mouse following MI surgery has further provided important insights into the longitudinal process of heart regeneration in individual, living animals. MRI of P1 mice post‐MI revealed how the heart grows during the neonatal period and maintains function during the regenerative process, as compared to P7 mice, which presented with classical signs of impaired cardiac output and pathological remodeling, as attributed to adult hearts following MI (Gunadasa‐Rohling et al., 2018).…”

Preclinical models of myocardial infarction: from mechanism to translation

“…Rolling them in bedding from the home cage prior to re‐introduction is essential to prevent maternal cannibalisation. Loss of function following injury and regain of structure and function during regeneration over the following 3–4 weeks can be successfully tracked in the lightly anaesthetised neonatal mouse using ECG‐gated high‐resolution ultrasound (Castellan, Thomson, et al, 2020) or MRI (Gunadasa‐Rohling et al, 2018).…”