Piecewise Pulse Wave Imaging (pPWI) for Detection and Monitoring of Focal Vascular Disease in Murine Aortas and Carotids In Vivo

Abstract

Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two common vascular diseases associated with mechanical changes in the arterial wall. Pulse Wave Imaging (PWI), a technique developed by our group to assess and quantify the mechanical properties of the aortic wall in vivo, may provide valuable diagnostic information. This work implements piecewise PWI (pPWI), an enhanced version of PWI designed for focal vascular diseases. Localized, sub-regional PWVs and PWI moduli ( EPWI ) were estimated within 2-4 mm wall segments of murine normal, atherosclerotic and aneurysmal arteries. Overall, stiffness was found to increase in the atherosclerotic cases. The mean sub-regional PWV was found to be 2.57±0.18 m/s for the normal aortas (n = 7) with a corresponding mean EPWI of 43.82±5.86 kPa. A significant increase ( (p ≤ 0.001)) in the group means of the sub-regional PWVs was found between the normal aortas and the aortas of mice on high-fat diet for 20 ( 3.30±0.36 m/s) and 30 weeks ( 3.56±0.29 m/s). The mean of the sub-regional PWVs ( 1.57±0.78 m/s) and EPWI values ( 19.23±15.47 kPa) decreased significantly in the aneurysmal aortas (p ≤ 0.05) . Furthermore, the mean coefficient of determination (r(2)) of the normal aortas was significantly higher (p ≤ 0.05) than those of the aneurysmal and atherosclerotic cases. These findings demonstrated that pPWI may be able to provide useful biomarkers for monitoring focal vascular diseases.

Figure 1

Timeline of the mouse experiments designed in the current study. (A20: mice on 20 weeks of high-fat diet, A30: mice on 30 weeks of high-fat diet)

Figure 2

Illustration of the post-processing methodology used in the current study

Figure 3

Sequence of PWI images every 1.25 ms (i.e. 10 frames) in a normal aorta. The axial wall velocities are color-coded and overlaid onto the B-mode image. Positive velocities (in red) represent upward motion while negative velocities (in blue) represent downward motion. The solid blue arrows indicate the propagation of the pulse wave from the proximal to the distal site ((a)-(d)).

Figure 4

Sequence of PWI images every 1.25 ms in an aorta of a mouse that has been under high-fat diet for 30 weeks. The solid blue arrows indicate the propagation of the pulse wave, while the solid red arrow indicates the stenotic region.

Figure 5

Sequence of PWI images every 1.25 ms in a mouse receiving angiotensin II. The solid blue arrows indicate the propagation of the pulse wave, while the solid red arrow indicates the aneurysmal region.

Figure 6

Sequence of PWI images every 1.25 ms in a carotid artery of a mouse that before the initiation of the high-fat diet. The solid blue arrows indicate the propagation of the pulse wave.

Figure 7

The sequence of PWI images every 1.25 ms in a carotid artery of a mouse that has been under high-fat diet for 30 weeks. The solid blue arrows indicate the propagation of the pulse wave, while the solid red arrow indicates the stenotic region.

Figure 8

Spatio-temporal imaging of pulse-wave propagation in murine aortas along with the piecewise linear regression of the 50% upstroke markers overlaid on each spatio-temporal plot. The sub-regional PWV and r² coefficient values are shown next to each segment, while the regional PWV and r² coefficient values for the whole imaged aortic region are shown on top of each spatio-temporal plot. The spatio-temporal plots above correspond to (a) a normal mouse aorta, (b) a stenotic mouse aorta after 30 weeks of high-fat diet and (c) an aneurysmal mouse aorta. In the latter two plots, the focal region of the disease is also indicated.

Figure 9

Spatio-temporal imaging of pulse-wave propagation in murine carotid arteries along with the piecewise linear regression of the 50% upstroke markers overlaid on each spatio-temporal plot. The sub-regional PWV and r² coefficient values are shown next to each segment, while the regional PWV and r² coefficient values for the whole imaged aortic region are shown on top of each spatio-temporal plot. The spatio-temporal plots above correspond to (a) a normal mouse carotid artery and (b) an atherosclerotic mouse carotid artery. In (a) a characteristic V-shape is delineated using dashed lines to indicate forward propagation of the forward pulse (left dashed line of the V) as well as the backward propagation of a reflected wave (right dashed line of the V).

Figure 10

Localized PWV and stiffness maps for the case of a mouse aorta (a) before the start of the high-fat diet, (b) after 20 weeks of high-fat diet and (c) after 30 weeks of high-fat diet. In the latter case stenosis has developed on the distal end of the aorta as indicated by the solid red arrow. Both the sub-regional PWVs and E_PWI have been color-coded and overlaid onto the B-mode images.

Figure 11

Localized PWV and stiffness maps for a mouse aorta (a) before the implantation of the angiotensin II pumps, (b) 6 days after pump implantation and (c) 16 days after pump implantation. In the latter case an aneurysm has developed on the distal end of the aorta as indicated by the solid red arrow. Both the sub-regional PWV and E_PWI have been color-coded and overlaid onto the B-mode images.

Figure 12

B-mode images along with localized PWV and stiffness maps for the case of a normal mouse carotid artery (a, b) and an atherosclerotic carotid artery (c, d). In the atherosclerotic carotid, stenosis has developed on the distal end of the artery as indicated by the solid red arrow (c, d). Both the sub-regional PWV and E_PWI values have been color-coded and overlaid onto the B-mode images (b, d).

Figure 13

Statistical results on seven normal (n = 7, Normal) aortas along with six aortas after 20 weeks of high-fat (n = 6, A20), four aortas (n = 4, A30) after 30 weeks of high-fat diet and six aneurysmal aortas (n = 6, AAA). (a) Mean sub-regional PWVs over the aortic wall averaged over the corresponding mouse population. (b) Mean sub-regional E_PWI values over the aortic wall averaged over the corresponding mouse population in each case. (c) Mean sub-regional r² coefficient over the aortic wall averaged over the corresponding mouse population in each case. (d) Standard deviation of the sub-regional PWVs over the whole imaged aortic wall averaged over the corresponding mouse population in each case. (e) Mean arterial wall thickness averaged over the corresponding mouse population in each case. (f) Mean peak PWI wall velocities over the whole imaged aortic wall averaged over the corresponding mouse population in each case. Error bars denote standard deviation and significances are marked on the plot.

Figure 14

Examples of using B-mode, B-mode-derived values and PWI-derived data to infer the nature of nonlinear propagation in (a) a normal mouse aorta, (b) an atherosclerotic mouse aorta and (c) an aneurysmal mouse aorta. In each case PWV and E_PWI maps are followed by plots of local diameter, arterial wall thickness measurements and local r² values.