Ultrasound Signal Enhancement of Halloysite Clay Nanotubes at Medical Diagnostic Frequencies

Aim of this work was to investigate the effect of ultrasound incident frequency on the echographic contrast enhancement power of an experimental drug delivery agent, halloysite clay nanotubes (HNTs), and to determine a suitable configuration in terms of both insonification frequency and particle concentration for an effective employment as targeted contrast agent. Various HNT concentrations (range 0.25-3.00 mg/mL) were dispersed in custom-designed tissue-mimicking phantoms and exposed to different ultrasound frequencies (7-11 MHz) through a conventional clinically-available echographic device. Off-line analysis included the evaluation of both amplitude of backscattered ultrasound signals and image brightness. Amplitude of HNT-backscattered signals showed a linear increase with particle concentration, while image brightness enhancement was limited by logarithmic compression effects. On the other hand, backscatter amplitude showed significant increments with increasing ultrasound frequency up to 10 MHz, then showing a concentration-dependent behavior without further enhancements. Overall, the most effective response was found when a 10-MHz ultrasound frequency was employed to insonify HNTs at a concentration of 1.5 mg/mL. In conclusion, the present study optimized the combination of incident ultrasound frequency and HNT concentration, in order to obtain an echographic image enhancement suitable for medical applications. Future dedicated studies will assess the feasibility of automatic detection of HNTs within echographic images and their possible employment as theranostic agents.