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.