The aim of this paper was to optimize the employment of a novel algorithm for acquisition and processing of medical ultrasound (US) signals to facilitate its clinical translation. The implemented procedure is dedicated to selective enhancement of nanoparticle (NP) contrast agents in echographic images and is based on the differences in US signal backscatter between NP-containing targets and more homogeneous objects. Previous preliminary studies verified the feasibility of this approach on silica nanospheres (SiNSs) dispersed at a constant volume concentration (0.7%) in agarose gel samples. The present extended these evaluations, addressing two issues of direct clinical interest: 1) safety: SiNSs were coated with a biocompatible layer made of polyethylene glycol (PEG) and the adopted NP volume concentration was reduced to 0.2%, which is in the nontoxic range and 2) reproducibility: a different phantom configuration was used, to verify the independence of algorithm performance from a specific target region shape. The obtained results demonstrated that the proposed method can be effectively applied to enhance the presence of PEG-coated SiNSs in the diameter range 160–660 nm at a low and biocompatible volume concentration: the combined employment of a phantom with a different geometry and a lower concentration of PEG-coated NPs, in fact, caused only slight variations in the suppression patterns of noncontrast echoes, without affecting the final diagnostic effectiveness of the investigated contrast detection scheme. This approach also provides specific advantages with respect to the available measurement techniques dedicated to the enhancement of targeted US contrast agents for molecular imaging purposes.
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