Relevance of the Magnetic Nanoparticles for Second Harmonic Ultrasound Generation: A New Approach for Magneto‐Acoustic Theranostic

We report experimental evidence of second harmonic (SH) ultrasound (US) generation by magnetic nanoparticles (MNPs) under pulsed radiofrequency electromagnetic fields (EMFs) (EMFs, 65 mT, 800 kHz, at 100 ms bursts). This pulsed EMF was fixed to avoid heating of the MNPs environment. We developed an experimental setup to detect the second harmonic (SH) signal without a temperature increase. This SH-US signal is observed only in samples containing MNPs. The use of non-MNPs does not show this contribution, which suggests that US generation is due to a magneto-acoustic effect in the MNPs. This could consider the use of this phenomenon as a diagnostic magneto-acoustic tomography (MAT) to detect MNPs localized at a malignancy region. We also report that magnetically aligned MNP clusters in gelatin significantly enhance the amplitude of the SH signal compared to that observed in non-aligned MNP samples. We demonstrate the capability for MNP detection by US scanning pulsed EMFs, which, combined with magnetic hyperthermia therapy, constitutes a new theranostic platform. Furthermore, pre-aligned anisotropic MNP structures significantly enhance the SH-US emission. This establishes a platform where spatial MNP orientation optimizes diagnostic sensitivity, enabling real-time image guidance for magnetic hyperthermia therapy.