Quantitative Estimates of the Variability of In Vivo Sonographic Measurements of the Mouse Aorta for Studies of Abdominal Aortic Aneurysms and Related Arterial Diseases

Abstract

Objectives Burgeoning interest in reducing the morbidity and mortality associated with abdominal aortic aneurysms (AAAs) has led to experimental strategies to elucidate the disease process and attain pharmacologic regression using the apolipoprotein E−/− (ApoE−/−) mouse model of angiotensin-induced AAAs and in vivo sonography. However, the variability of in vivo sonographic measurements of the mouse aorta has not been established. Thus, our purpose was to determine quantitative estimates of the variability of in vivo sonographic measurements of the mouse aorta as a guide for the design and assessment of studies focused on regression of AAAs and related arterial diseases. Methods We used Bland-Altman, locally weighted scatterplot-smoothing regression, and resampling (bootstrapping) methods for variability analyses of multiple in vivo short- and long-axis sonographic measurements of ApoE−/− mouse aortas. We measured distinct aortic sites in vivo at the baseline and after angiotensin-induced AAAs and ex vivo using digital calipers. Results We analyzed 236 data points from 10 male mice (14 weeks old; mean weight ± SD, 29.7 ± 1.6 g). Overall intramouse differences between short- and long-axis and in vivo and ex vivo measurements were 0.038 (95% confidence interval [CI], 0.031–0.046) and 0.085 (95% CI, 0.062–0.109) mm, respectively. Intermouse differences in short-axis measurements were 0.047 (95% CI, 0.042–0.053), 0.049 (95% CI, 0.044–0.055), and 0.039 (95% CI, 0.036-0.042) mm for infrarenal, suprarenal, and thoracic measurements, respectively; differences in long-axis measurements were 0.054 (95% CI, 0.044–0.064), 0.029 (95% CI, 0.024–0.034), and 0.046 (95% CI, 0.037–0.054) mm. Bland-Altman and locally weighted scatterplot-smoothing analyses showed excellent agreement between measures with no variation in discrepancies vis-à-vis the target measurement. Conclusions These data establish previously undefined estimates of measurement variability relevant for in vivo sonographic studies of AAA regression in a commonly studied mouse model.

Angiotensin II Mobilizes Spleen Monocytes to Promote the Development of Abdominal Aortic Aneurysm in Apoe −/− Mice

“…Monocyte subsets decreased back to the PBS level after 14 days and remained stable until the end of treatment ( Figure IIA in the online-only Data Supplement), showing that early mobilization of monocyte subsets is transient and may account for early aortic macrophage accumulation during AngII delivery. As a note, 14 days of AngII delivery significantly increased the pool of monocytes in the BM and the spleen, despite no change in the blood ( Figure IIB in the online-only Data Supplement).Despite controlled experimental conditions, the heterogeneity in AAA lesion development reported previously 34 and observed in our hands prompted us to evaluate whether changes in blood monocyte levels could be an indicator of later aneurysm formation ( Figure 2C). We found that in mice that did not develop AAA, monocyte levels remained stable over the course of the experiment and were comparable with monocyte levels observed in response to PBS.…”

“…Despite controlled experimental conditions, the heterogeneity in AAA lesion development reported previously 34 and observed in our hands prompted us to evaluate whether changes in blood monocyte levels could be an indicator of later aneurysm formation ( Figure 2C). We found that in mice that did not develop AAA, monocyte levels remained stable over the course of the experiment and were comparable with monocyte levels observed in response to PBS.…”

Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms

“…In the first arm, mice were exposed to 5 mg/kg/week of B(a)P (98 % pure; Sigma) for 42 days, and in the second arm to 0.71 mg/kg/day for 60 days. Benzo(a)pyrene exposure was done via oral gavage, and AngII exposure (1000 ng/kg/min 9 2 weeks) occurred via subcutaneous osmotic mini pumps (Alzet Model 2004, Durect Corporation, CA) as previously described [11]. In the B(a)P ?…”

The effect of isoflavones on diameter change of hypo estrogenic rat abdominal aorta measured by 12- MHz ultrasound

“…This measurement also showed that the biggest variation happened in suprarenal and infrarenal segments, which were caused by remodeling as the result of aneurysm and atherosclerosis process. 8,21 Variation also happened in the measurement result by using ultrasound compared with measurement to histologic specimen. Some factors causing this are measurement location may not be exactly the same, since it is impossible to give marker to state measurement location.…”

“…The use of ultrasound to evaluate blood vessels of experimental animal in a research to estimate the abdominal aortic aneurysm regression was initiated by Wang, et al 5 Sampson, et al state that the measurement of in vivo rat's abdominal aortic diameter using high frequency ultrasound shows that the result is not different from that using the in vitro measurement. 8 Another study conducted by Radu et al compared the measurement of ascending aorta using US with 9 MHZ probe with that of video microscopy, and the result shows no difference as well. 9 Blood vessels have walls consisting of three concentric layers, which are tunica intima, tunica media, and tunica adventitia.…”