Objective: Nanotheranostic systems integrate therapeutic and diagnostic procedures using nanotechnology. This type of approach has enabled the development of methods for early detection and treatment of different pathologies. Magnetic hyperthermia (MH) has been proposed as an alternative or complementary method of cancer therapy. However, challenges such as delivering and localizing the magnetic nanoparticles (MNPs) within tissues and monitoring the temperature during the treatment hinder this technique to be effectively translated into clinical routine. Therefore, in this study a theranostic platform has been proposed and examined to address two main issues, localizing MNPs and real-time temperature monitoring, for preclinical MH. Methods: The system integrates magnetomotive (MMUS) and thermal ultrasound imaging with MH. An ultrasound device was used to acquire MMUS images to detect MNPs, and ultrasound thermometry to monitor the temperature. This platform was designed such that a single coil generated the magnetic field for MMUS and MH. The feasibility of the system was examined using a tissue mimicking phantom containing an inclusion filled with zinc substituted magnetite NPs. Results: These MNPs were effectively used as contrast agent for MMUS and to generate heat during MH. In addition to localizing MNPs, real-time two-dimensional temperature maps were obtained with substantial concordance (pc>0.97) with invasive measurements using fiber optic thermometer. The heating rate was proportional to the displacements in MMUS (r=0.92). Conclusion: Ultrasound thermometry was successfully used to monitor the temperature during MH. In addition, it was shown that acquiring MMUS images prior to MH can qualitatively predict the temperature distribution of the MNP-laden regions.

Photoacoustic imaging (PAI) combines optical contrast with ultrasound spatial resolution and can be obtained up to a depth of a few centimeters. Hand-held PAI systems using linear array usually operate in reflection mode using a dark-field illumination scheme, where the optical fiber output is attached to both sides of the elevation plane (short-axis) of the transducer. More recently, bright-field strategies where the optical illumination is coaxial with acoustic detection have been proposed to overcome some limitations of the standard dark-field approach. In this paper, a novel multiangle long-axis lateral illumination is proposed. Monte Carlo simulations were conducted to evaluate light delivery for three different illumination schemes: bright-field, standard dark-field, and long-axis lateral illumination. Long-axis lateral illumination showed remarkable improvement in light delivery for targets with a width smaller than the transducer lateral dimension. A prototype was developed to experimentally demonstrate the feasibility of the proposed approach. In this device, the fiber bundle terminal ends are attached to both sides of the transducer’s long-axis and the illumination angle of each fiber bundle can be independently controlled. The final PA image is obtained by the coherent sum of subframes acquired using different angles. The prototype was experimentally evaluated by taking images from a phantom, a mouse abdomen, forearm, and index finger of a volunteer. The system provided light delivery enhancement taking advantage of the geometry of the target, achieving sufficient signal-to-noise ratio at clinically relevant depths.

Theranostic strategies are advancing personalized medicine, with particularly impactful applications in cancer treatment. Among these, magnetic hyperthermia (MH) stands out, employing high-frequency magnetic field (MF) and magnetic nanoparticles (MNPs) to selectively target and heat cancerous cells. Real-time temperature monitoring and MNP localization, however, remain significant challenges in clinical translation. Previous studies have shown that magnetomotive ultrasound (MMUS) effectively addresses these challenges. Developing an automated and synchronized transition between MMUS and MH within an integrated platform is, however, challenging due to incompatible frequency requirements, with MH operating in the 0.1–1 MHz range and MMUS requiring lower frequency MF below 100 Hz. This study aimed to develop an automated platform enabling interleaved MF applications using a single excitation coil for both MH and MMUS. We propose using a high-frequency ferrite transformer to couple both generators for automated electronic switching. The platform used a multipurpose air-core inductor capable of producing MF pulses up to 205 kA/m (with currents reaching 2.16 kA) for MMUS, interleaved with MH stimulation at 170 kHz and 28 kA/m. The MH framework induced an $8~^{\circ }$ C temperature increase in 1 cm3 ferrofluid samples at an MF strength of 15 kA/m. Preliminary phantom experiments demonstrated the system’s capability to localize MNPs noninvasively, monitor thermal variations up to $1~^{\circ }$ C, and visualize tissue property changes during MH, showcasing promising integration of MMUS and MH.

Keywords Photoacoustic imaging; Temperature monitoring; Hyperthermia; Genetic algorithm

Magnetomotive ultrasound (MMUS) stands out as a promising and effective ultrasound-based method for detecting magnetic nanoparticles (MNPs) within tissues. This innovative technique relies on the precise estimation of micrometric displacements induced by the interaction of an external magnetic field with MNPs. Pulsed MMUS has emerged as a strategic alternative to address limitations associated with harmonic excitation, such as heat generation in amplifiers and coils, frequency-dependent tissue mechanical responses, and prolonged magnetic field rise times. Despite the growing interest in MMUS, the devices conventionally employed to excite the coil are not specifically tailored to generate intense magnetic fields while minimizing interference with the transient behavior of induced displacements. To bridge this gap, our work introduces the design and fabrication of two pulse generators: one based on a capacitor-discharge circuit and the other on a resonant-inverter circuit. We evaluated the performance of these pulse generators by considering parameters such as the magnetic field generated, rise and fall times, and their ability to supply sustained current for varied pulse widths across different pulse repetition frequencies. Furthermore, we carried out a practical MMUS implementation using tissue-mimicking phantoms, demonstrating the capability of both devices to achieve magnetic fields of up to 1 T and average displacements of 25 µm within the phantom. In addition, we estimated the shear wave velocity, effective shear modulus, and their temperature-dependent variations. Our findings highlight the versatility and efficacy of the proposed pulse generators and emphasize their potential as low-cost platforms for theranostic applications, enabling the assessment of targeted entities within biological tissues.