Multi-Frequency Differential Image Enhancement of Nanosized Ultrasound Contrast Agents

Aim of the present work was to perform a detailed experimental investigation on the applicability ranges of a novel ultrasound (US) imaging method, that has been recently proposed by our research group in order to facilitate the detection of targeted nanosized contrast agents on diagnostic echographic images. In our previous investigation, in fact, we demonstrated the possibility of selectively suppressing non-contrast echoes in US images through a new contrast detection protocol, including a novel broadband pulse sequence employing two different US frequencies and a two-step image processing algorithm. Feasibility of this approach was preliminarily verified on 330-nm silica nanospheres (SiNSs) dispersed in agarose gel phantoms. In the present work, we investigated the effectiveness of the same approach employing a different clinically-available echographic device and adding the following new experimental conditions: 1) two further sizes of SiNSs (160 nm and 660 nm) were tested; 2) the effects of lower levels of incident acoustic pressure were studied; 3) a different couple of lower US frequencies was employed. Obtained results demonstrated that the proposed method can be effectively applied to enhance the presence of SiNSs in the whole range 160-660 nm employing US pulses at conventional diagnostic frequencies and it seemed particularly suited to be employed in combination with low acoustic pressures. Furthermore, the tested imaging technique shows very promising perspectives for a prompt translation into clinical contexts, given its suitability for real-time imaging with constant spatial resolution employing commercially-available echographic devices.