A preclinical ultrasound method for the assessment of vascular disease progression in murine models

Abstract

Introduction: Early detection of vascular alterations associated with disease can play a key role in diagnosis and evaluation of treatment strategies. Ultrasound is commonly used for real-time assessment of human blood vessels but the efficacy of preclinical ultrasound at providing a quantitative assessment of mouse models of vascular disease is relatively unknown. In this study, preclinical ultrasound was used in combination with a semi-automatic image processing method to track arterial distension alterations in mouse models of abdominal aortic aneurysm (AAA) and atherosclerosis. Methods: Longitudinal B-mode ultrasound images of the abdominal aorta were acquired using a preclinical ultrasound scanner. Arterial distension was assessed using a semi-automatic image processing algorithm to track vessel wall motion over the cardiac cycle and a standard, manual analysis method was applied for comparison. Results: Mean arterial distension was significantly lower in AAA mice between day 0 and day 7 post-onset of disease (p<0.01) and between day 0 and day 14 (p<0.001), while no difference was observed in sham control mice. The manual method detected a significant decrease (p<0.05) between day 0 and day 14 only. Atherosclerotic mice showed alterations in arterial distension relating to genetic modification and diet. Arterial distension was significantly lower (p<0.05) in Ldlr-/-(++/-) mice fed high fat western diet when compared with both wild type (++/++) mice and Ldlr-/-(++/-) mice fed chow diet. The manual method did not detect a significant difference between these groups. Conclusions: Arterial distension can be used as an early marker for the detection of arterial disease in small animal models. The semi-automatic analysis method provided increased sensitivity to differences between experimental groups when compared to the manual analysis method. Furthermore, a retrospective power calculation revealed that use of the semi-automatic method reduces the number of animals required per experiment.

Biomechanical changes of the common carotid artery and internal jugular vein in patients with multiple sclerosis

“…In the current study, a significant raise in the IJV's pressure in patients with MS compared to healthy individuals was observed. Increasing venous pressure in the superior sagittal sinus in MS A c c e p t e d A r t i c l e patients has been also reported by Bateman et al [24,25]. In this study, the radial strain of the CCA wall in patients with RRMS and PPMS was reduced by 38% and 25%, respectively.…”

“…In the current study, the compliance and distensibility of the IJV were higher in the healthy group, and significantly higher IJV pressure was observed in patients with MS compared to healthy individuals. Increased venous pressure in the superior sagittal sinus in MS patients has also been reported by Bateman et al [ 24 , 25 ]. In this study, the radial strain of the CCA wall in patients with RRMS and PPMS was 38% and 25% lower, respectively, and the elastic modulus of patients with RRMS and PPMS was 47% and 9% higher, respectively, than in healthy individuals.…”

The Progress of Advanced Ultrasonography in Assessing Aortic Stiffness and the Application Discrepancy between Humans and Rodents

“…Importantly, studies have shown that B-mode images presented a higher reproducibility in the measurements of Valsalva’s sinuses in patients with suspected Marfan syndrome [ 48 ]. B-mode has been applied to the analysis of arterial distension of the carotid arteries and the DAAo in preclinical studies of disease [ 21 ]. Measurements of arterial stiffness at different vascular tree sites do not seem to be interchangeable, but there is a correlation [ 49 ].…”

“…It has been shown that the reduced circumferential strain is correlated with an increased elastin fragmentation in fibrillin-1 hypomorphic mice [ 44 ]. In addition, a novel semi-automatic method for tracking the changes of vessel lumen diameter with B-mode images was also applicable in mouse models of vascular disease by measuring the arterial diameter over the entire B-mode cine loops [ 21 ].…”

“…Small animals, especially rodents (rats and mice), have also been widely used in the basic science research of vascular diseases, particularly in mechanistic molecular studies with the advantages of various genetic-modified models [ 21 ]. These small animal models have the feasibility to perform analysis that is not practical in humans, such as surgery, genetic and pharmacological inventions, invasive measurements, and tissue/cell isolations.…”