The Application of High-Resolution Ultrasound for Assessment of Cardiac Structure and Function Associated with Developmental Toxicity

Abstract

Congenital heart defects (CHD) are the most prevalent anomaly both clinically and in laboratory animal species. Historically, it was difficult to assess the longitudinal progression or repair of such anomalies because assessment methodologies were too invasive (gross exams and/or histology). Recently, technological advances in the field of diagnostic imaging have led to the manufacture of high-resolution ultrasound (HRUS), capable of characterizing both embryonic and maternal cardiovascular structure and function in small animals (rat and mouse). HRUS is relatively noninvasive, facilitating the longitudinal assessment of heart development throughout gestation and postnatally, providing a comprehensive evaluation of changes in cardiovascular performance following toxicant exposure.

Described herein is a brief overview of important theoretical and practical considerations when applying HRUS to understand the impact of perturbations on the fetal heart. Examples are given from our own work to help the reader interpret their own HRUS images and more readily identify anomalies in utero. In addition to embryonic assessment, maternal pathologies may adversely affect the cardiovascular performance of the conceptus indirectly. Umbilical blood flow is particularly vulnerable to such effects and procedures to assess this endpoint are described. Neonatal rats, born with CHD, may respond pathologically to cardiovascular challenges as they mature, and we outline the use of HRUS to evaluate cardiac performance over the lifetime of the animal. Some of the caveats related to HRUS are discussed, particularly with the emphasis on how this may impact experimental design.