A step-wise approach for analysis of the mouse embryonic heart using 17.6 Tesla MRI

Abstract

BackgroundThe mouse embryo is ideal for studying human cardiac development. However, laboratory discoveries do not easily translate into clinical findings partially because of histological diagnostic techniques that induce artifacts and lack standardization. AimTo present a step-wise approach using 17.6T MRI, for evaluation of mice embryonic heart and accurate identification of congenital heart defects. Subjects17.5-embryonic days embryos from low-risk (non-diabetic) and high-risk (diabetic) model dams. Study designEmbryos were imaged using 17.6Tesla MRI. Three-dimensional volumes were analyzed using ImageJ software. Outcome measuresEmbryonic hearts were evaluated utilizing anatomic landmarks to locate the four-chamber view, the left- and right-outflow tracts, and the arrangement of the great arteries. Inter- and intra-observer agreement were calculated using kappa scores by comparing two researchers' evaluations independently analyzing all hearts, blinded to the model, on three different, timed occasions. Each evaluated 16 imaging volumes of 16 embryos: 4 embryos from normal dams, and 12 embryos from diabetic dams. ResultsInter-observer agreement and reproducibility were 0.779 (95% CI 0.653–0.905) and 0.763 (95% CI 0.605–0.921), respectively. Embryonic hearts were structurally normal in 4/4 and 7/12 embryos from normal and diabetic dams, respectively. Five embryos from diabetic dams had defects: ventricular septal defects (n=2), transposition of great arteries (n=2) and Tetralogy of Fallot (n=1). Both researchers identified all cardiac lesions. ConclusionA step-wise approach for analysis of MRI-derived 3D imaging provides reproducible detailed cardiac evaluation of normal and abnormal mice embryonic hearts. This approach can accurately reveal cardiac structure and, thus, increases the yield of animal model in congenital heart defect research.