Targeted ultrasound contrast materials (gas-filled microbubbles carrying ligands to endothelial selectins or integrins) have been investigated as potential molecular imaging agents. Such microbubbles normally exhibit good targeting capability at the slower flow conditions. However, in the conditions of vigorous flow, binding may be limited. Here, we describe a microbubble capable of efficient binding to targets both in slow and fast flow (exceeding 4 dyne/cm(2) wall shear stress) using a clustered polymeric form of the fast-binding selectin ligand sialyl Lewis(X). Microbubbles were prepared from decafluorobutane gas and stabilized with a monolayer of phosphatidylcholine, PEG stearate and biotin-PEG-lipid. Biotinylated PSLe(x) (sialyl Lewis(X) polyacrylamide) or biotinylated anti-P-selectin antibody (RB40.34) was attached to microbubbles via a streptavidin bridge. In a parallel plate flow chamber targeted adhesion model, PSLe(x) bubbles demonstrated specific adhesion, retention and slow rolling on P-selectin-coated plates. Efficiency of firm targeted adhesion to a P-selectin surface (140 molecules/microm(2)) was comparable for antibody-carrying bubbles and PSLe(x)-targeted bubbles at 0.68 dyne/cm(2) shear stress. At fast flow (4.45 dyne/cm(2)), PSLe(x)-targeted bubbles maintained their ability to bind, while antibody-mediated targeting dropped more than 20-fold. At lower surface density of P-selectin (7 molecules/microm(2)), targeting via PSLe(x) was more efficient than via antibody under all the flow conditions tested. Negative control casein-coated plates did not retain bubbles in the range of flow conditions studied. To confirm echogenicity, targeted PSLe(x)-bubbles were visualized on P-selectin-coated polystyrene plates by ultrasound imaging with a clinical scanner operated in pulse inversion mode; control plates lacking targeted bubbles did not show significant acoustic backscatter. In vivo, in a murine model of inflammation in the femoral vein setting, targeting efficacy of intravenously administered PSLe(x)-microbubbles was comparable with targeting mediated by anti-P-selectin antibody, and significantly exceeded the accumulation of non-targeted control bubbles. In the inflamed femoral artery setting, PSLe(x)-mediated microbubble targeting was superior to antibody-mediated targeting.

The thermoacoustic resonance effect induced by the interaction of multiburst modulated microwave pulses with biological tissue can be used to study the absorption and mechanical properties of tumorous tissues. Here, the mechanism of the thermoacoustic resonance response of the tumor is simulated using the finite element method, and the tumor size dependence on the resonance frequencies is investigated. The simulation results show that the maximum acoustic signal amplification depends on the microwave pulse modulation frequency and consequently the tumor radius. The results also indicate that the resonance frequencies decrease with an increase in tumor size. Utilizing the modulation frequency corresponding to the maximum amplification facilitates the use of microwave pulses with lower power and increases the safety of thermoacoustic imaging, resulting in the reduction of cost and risk of thermoacoustic tomography systems.

Diffuse optical tomography (DOT) is an emerging oncological imaging modality that is based on a near-infrared optical technique. DOT provides the spatial volume and depth of tumors by determination of optical properties of biological tissues, such as the absorption and scattering coefficients. During a DOT, the optical fibers are kept in contact with biological tissues that introduce a certain amount of pressure on the local biological tissue. Due to this pressure, the shape of the organ, for instance a breast, deforms. Moreover, this pressure could influence the intrinsic characteristics of the biological tissue. Therefore, pressure can be an important parameter in DOT. In this paper, the effects of pressure on the determination of the size and position of a tumor in biological phantoms are studied. To do so, tissue-like phantoms that are made of intralipid, Indian ink, and agar are constructed. Defects with optical properties similar to those of tumors are placed inside the phantoms. Then various values of pressure are applied to the phantoms. Subsequently, the optical properties of phantoms as well as the position and size of the tumor are reconstructed by inverse models based on the boundary integral method. The variations of reconstructed data induced by pressure are studied. The results demonstrate that pressure causes an increase in the scattering coefficient.

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