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Atherosclerosis is defined as a focal, inflammatory, and fibro-proliferative response to endothelial injury. The development of atheromatous lesions in the coronary tree is predominantly a quiescent asymptomatic process without any clinical manifestations. The unpredictable and acute nature of cardiovascular complications such as vulnerable plaque rupture makes diagnosis and treatment of this disease an outstanding medical challenge. We investigate non-invasive techniques that facilitate mechanical measurements at the microscopic level, which can then be directly correlated to biomarker localization within lesion sites. To characterize these sites in vitro, we used time-resolved scanning acoustic microscopy (TRSAM). This technique allows for non-invasive interrogation of tissue samples with optical resolution at the micrometer scale. Furthermore, we combined TRSAM with micro-Raman (micro-RS) spectroscopy to investigate plaque morphology with regard to specific biomarkers. We characterized mechanoelastic and biochemical regions containing high cholesterol, phosphate, and carbonate apatite that are characteristic of atherosclerotic lesions. The mechanoelastic evaluation of these regions was determined using TRSAM. Calcified lesions, for example, exhibit ultrasonic velocities of 1810 m/s ± 25 m/s and are more rigid and stiffer than normal blood vessel tissues.

Ultrasound-mediated drug and gene delivery offers a variety of exciting possibilities for improved localized treatment of vascular- and cancer-related diseases. This therapeutic application benefits from the use of the acoustic radiation force that facilitates the exposure for enhanced binding due to ligand-receptor interactions. The main merits of ultrasound lie in the transient increase of cell permeability without exposing the cell corpus to any detrimental and irreversible side-effects. Nonetheless, the related underlying molecular and cellular pathways of ultrasound-induced permeability and the subsequent recovery of cells have not been answered satisfactorily. Real-time studies of cell behavior during and past-ultrasound exposure have been obstructed by the lack of appropriate techniques. The Electric-Cell Impedance Sensing (ECIS) technique is an attractive way of studying cell permeability changes in real-time. Its nanoscale sensitivity and speedy acquisition of data allows for the accurate and timely monitoring of cell behavior. Our preliminary results suggest that cells recover within 24 - 36 hours post-exposure. During this time window the cells undergo drastic changes exhibiting an increased permeability of 2.4 ± 0.6 Ω•cm2 compared to 3.8 ± 0.5 Ω•cm2 that normal untreated cells exhibit.

Targeted ultrasound contrast agents (UCA) offer a novel, potential method for diagnostic imaging of biofilm infections. Currently, there is no established method for molecular imaging of in vitro biofilm infections with any type of modality. For infective endocarditis, the case of biofilm formation on damaged or diseased heart valves, an early diagnostic method might greatly reduce the associated high mortality rate. Fluorescently labeled lectins were used with targeted ultrasound contrast agents in conjunction with epifluorescence microscopy and time‐resolved scanning acoustic microscopy for visualization and characterization of the extracellular polymeric substances (EPS) of two types of infectious biofilms (Staphylococcus aureus and Pseudomonas aeruginosa). Noninvasive acoustic measurements of the biofilms were conducted at high‐frequency (100 MHz) with a time‐resolved scanning acoustic microscope. Measurements of the reflection and transmission coefficients, over a broad frequency spectrum for a range...