Author: David Alejandro Collazos Burbano, Antonio Adilton Oliveira Carneiro, Paul L. Carson, Jose Eduardo Freire, Theo Zeferino Pavan, Joao Henrique Uliana, Nicholas Zufelato 👨🔬
Affiliation: University of São Paulo, University of Michigan, University of Sao Paulo 🌍
Purpose: Develop a theranostic platform that integrates magnetic hyperthermia (MH), ultrasound, and magnetic nanoparticles (MNPs) to improve diagnosis, treatment, and monitoring of hyperthermia procedures using phantom and ex vivo tissue models.
Methods: Manganese ferrite MNPs were used in MH procedures to generate heat under an alternating magnetic field, enabling localized thermal ablation of bovine liver tissue ex vivo. Magnetomotive ultrasound (MMUS) monitored the distribution of the injected MNPs by mapping the magnetically induced displacement via ultrasound, while rheological analyses extract tissue viscoelastic parameters based on MH-induced changes. The thermal dose was quantified using the cumulative equivalent minute at 43°C (CEM43), and the physical model was validated using phantoms with a homogeneous MNP distribution.
Results: Validation with phantoms uniformly distributed with MNPs demonstrated a Young's modulus of 10.8 kPa using a conventional mechanical testing system and a spring constant of 2.2 N/m using the method proposed in this paper. The viscosity was estimated in 0.6 Pa·s by using acoustic radiation force and the Kelvin-Voigt model, while the viscous damping coefficient was 3.5 g/s using the proposed method. MMUS monitoring of injected MNPs in ex vivo samples revealed that magnetic displacement reached a steady-state regime 15 minutes post-injection, indicating stable interaction with the surrounding tissue matrix. Significant correlations were observed between viscoelastic parameters and MH-induced changes, including a 56% increase in the spring constant and a 63% increase in the viscous damping coefficient, corresponding to a CEM43 value of 504 minutes.
Conclusion: The platform demonstrated significant potential for theranostic applications, enabling effective monitoring of MNP distribution and localized temperature increases in hyperthermia treatments. The proposed model showed agreement with traditional methods for the extraction of viscoelastic parameters and provided a valuable metric correlated with the thermal dose deposition in the target regions.