Ultrasound imaging for assessing aortic phenotypes: A preclinical tool for measuring cardiac disease model progression and therapeutic effect

Cardiac dysfunction is a common feature of numerous diseases, ranging from metabolic disorders like Mucopolysaccharidosis Type 1 (MPS I), a.k.a. Hurler syndrome to neuromuscular disorders such as Myotonic Dystrophy type 1 (DM1). The ability to quantify cardiac abnormalities in animal models of these diseases is a valuable translational tool for preclinical testing of novel therapeutic approaches. In contrast to methods that measure the left ventricle (LV) phenotype, we employed ultrasound imaging to assess the ascending aortic diameter and ascending aortic blood velocity. We imaged two disease models - MPS I Hurler mouse model and DM1 mouse model (DMSXL) - using the Vevo2100 platform. Ascending aortic diameter in the proximal thoracic aortic region and ascending aortic blood velocity just before the branching point of the brachiocephalic artery were measured as rapid imaging readouts. In addition, histopathology was performed on relevant tissue samples. The two mouse models demonstrate opposing aorta phenotypes. Hurler mice had a dilated aorta and slightly increased blood velocity with disease progression, while the aorta diameter in DMSXL mice narrowed and had a blood velocity decrease as the disease progressed. In the Hurler model, we demonstrated that a single dose of adeno-associated virus (AAV) delivered gene therapy provides aortic phenotype improvement. In the DMSXL model, we established aortic phenotype criteria at baseline. Ultrasound imaging of aortic diameter and blood velocity can offer objective and longitudinal assessments of disease progression and treatment efficacy in real time. This method might therefore have noninvasive clinical applicability as phenotype indicator of cardiac dysfunction.