A Dual Frequency Ultrasound Technique for the Improved Detection of Bimodal Nanosized Contrast Agents

Every biomedical imaging technique exploits different physical principles and can provide peculiar information, which is often unachievable with different techniques and can be further enhanced by the employment of suitable contrast agents (CAs). However, each imaging technique typically requires its own specific CAs, with corresponding increments of procedure duration, costs and invasiveness for the patients, who should undergo two injections. In the last years, great effort has been addressed toward the development of multimodal CAs that can be real-time detected by different techniques. In this context, we developed a new type of bimodal nanoparticles (NPs), consisting of silica nanospheres (NSs) covered by an outer shell of smaller superparamagnetic NPs, to be used as dual-mode imaging CAs for ultrasound and magnetic resonance imaging techniques. Aim of the present study was to evaluate the echographic detectability of these bimodal NPs through a recently developed algorithm that was originally implemented to detect pure silica NSs. In particular, we performed a series of "in vitro" experiments on custom-designed tissue-mimicking phantoms, focused on a specific objective of direct clinical interest: the detection of multimodal NPs with a diameter of about 330 nm at a low and biocompatible volume concentration (0.2%). The obtained results demonstrated the possibility of deleting the US echoes coming from structures other than NPs with high effectiveness, therefore enhancing the brightness of nanosized contrast agents in the final diagnostic images. The effectiveness of the proposed method shows very promising perspectives for future clinical applications.