Aim of this work was to investigate the automatic echographic detection of an experimental drug delivery agent, halloysite clay nanotubes (HNTs), by employing an innovative method based on advanced spectral analysis of the corresponding "raw" radiofrequency backscatter signals. Different HNT concentrations in a low range (5.5-66 × 10(10) part/mL, equivalent to 0.25-3.00 mg/mL) were dispersed in custom-designed tissue-mimicking phantoms and imaged through a clinically-available echographic device at a conventional ultrasound diagnostic frequency (10 MHz). The most effective response (sensitivity = 60%, specificity = 95%), was found at a concentration of 33 × 10(10) part/mL (1.5 mg/mL), representing a kind of best compromise between the need of enough particles to introduce detectable spectral modifications in the backscattered signal and the necessity to avoid the losses of spectral peculiarity associated to higher HNT concentrations. Based on theoretical considerations and quantitative comparisons with literature-available results, this concentration could also represent an optimal concentration level for the automatic echographic detection of different solid nanoparticles when employing a similar ultrasound frequency. Future dedicated studies will assess the actual clinical usefulness of the proposed approach and the potential of HNTs for effective theranostic applications.
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