Nanoparticle-Enhanced Therapeutic Ultrasound

I was the first student who started the FUS research in AI for manufacturing lab. During my Ph.D. studies at the University of Waterloo, I designed, modeled, and fabricated a FUS system with application to non-invasive cancer treatment. Using the developed system, I conducted a comprehensive study of the feasibility and the feature effects of various nanoparticle (NP)-based agents during the FUS heating procedures, including gold NPs (AuNPs), magnetic NPs (MNPs), and carbon nanotubes (CNTs). These studies provided valuable results on the potential effects of nanoscale agents to improve FUS’s heating mechanism at low ultrasonic powers, thereby addressing the safety concerns regarding the FUS treatment with high ultrasonic powers. My works on NP-enhanced FUS were published in well-known journals in the field of biomedical engineering and nanotechnology,  IEEE Transactions on Biomedical Engineering (IF: 4.538) Nano Futures (IF: 3.306), Nanotechnology (IF: 3.874), and IEEE Transactions on NanoBioscience (IF: 2.935).

NP-enhanced HIFU

 

Focused ultrasound (FUS) therapy is a new non-invasive method that uses ultrasonic energy to treat a range of health disorders and tumors. Despite the great potential for cancer treatment, the FUS therapies for the breast and abdominal regions have not been granted FDA approval yet. One of the major challenges of FUS is the collateral damage due to the use of high ultrasonic energy during the thermal treatment. One promising strategy to enhance the heating mechanism of FUS, thereby reducing its side effects, is to use nanoparticles (NPs) as ultrasound absorption agents. To improve the therapeutic mechanism of NP-enhanced FUS, it is essential to better understand the physics of the interaction between ultrasonic waves and NPs, and to clarify the effects of crucial parameters related to the NPs that can affect FUS’s heating mechanism. To this end, I conducted a comprehensive study on the potential effects of various NP-based therapeutic agents during the FUS treatment.

Experimental Setup:

The system was comprised of three major units: a FUS generation mechanism for thermal ablation procedure, an ultrasound imaging unit for real-time monitoring of the FUS process, and an advanced robotic mechanism for accurate positioning of target regions. In the FUS generation system, a single-element transducer having a concave shape was used to therapeutic ultrasound. The required signal to drive the transducer at the desired frequency was produced by a function generator and amplified by a RF amplifier. The amplified signal passed through an acoustic matching network designed to realize output resistance of 50 Ω before being routed to the transducer. A three-dimensional positioning system was assembled to the setup to move the transducer along the beam axis as well as other orthogonal directions. Finally, a thermocouple was installed at the focused region to measure the temperature and monitor the heating mechanism of FUS. To ensure that the cavitation did not occur during the thermal ablation, the temperature rise was carefully monitored during the HIFU insonation, as the occurrence of cavitation might cause a sudden jump in the temperature profile.

Agar-based phantoms as in vitro media were developed to monitor the heating mechanism of FUS and also to host NPs with different features. Agar phantoms have similar porous structures and thermo-acoustic properties to biological tissues and have been widely used in literature for nano-drug delivery and hyperthermia studies. The fabricated phantoms were used to take control of the distribution of NPs inside the suspending medium. They form realistic tissue models with well-defined thermo-acoustic properties so as to investigate the feature effects of NPs.

Experimental setup

A series of experiments were conducted using tissue-mimicking phantoms embedded with NPs to examine the enhancing effects of various NPs during the FUS heating procedures. The experiments included magnetic NPs (MNPs), gold NPs (AuNPs), and carbon nanotubes (CNTs). The results showed that the presence of NPs at the focused region significantly enhanced the heating mechanism of FUS by increasing the absorption rate of acoustic energy and the temperature rise during the FUS procedure. Besides, the efficacy of NPs was studied when exposed to ultrasonic fields at different ranges of powers and frequencies. The results showed that the increase of NP size and volume concentration greatly enhanced the FUS heating parameters (i.e., the absorption rate of acoustic energy and the temperature rise at the focal region). It was also proved that the effects of NPs during the FUS heating procedures were further improved by increasing the power and frequency of the ultrasonic field.

Magnetic NPs (MNPs)-enhanced FUS ablation therapy

The enhancing effects of MNPs on temperature rise profile, monitored during the FUS ablation procedures

temperature rise

MNPs enhanced the absorption rate of acoustic energy by the targeted medium during the FUS ablation procedures 

absorption rate

 

Carbon Nanotubes (CNTs)-enhanced FUS ablation therapy

The temperature rises profile at the focal region show the enhancing effects of CNTs on FUS's ablation procedure 

cnt1

The enhancing effects of CNTs on the absorption rate of acoustic energy and its conversion to heat at the focal region

absorption

 

Gold NPs (AUNPs)-enhanced FUS ablation therapy

The dose effects of AuNPs on FUS's temperature rise procedures at the focal region (A precision temperature monitoring was conducted)

 gold

The enhancing effects of AuNPs on the absorption rate of acoustic energy at the focal region

absorption