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Enhanced Thermal Ablation of Biomaterials Using High-Intensity Focused Ultrasound (HIFU) Energized Nano-particles

Devarakonda, Surendra B
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1544001995977567

Abstract Details

2018, PhD, University of Cincinnati, Engineering and Applied Science: Mechanical Engineering.
High-intensity focused ultrasound (HIFU) has gained increasing popularity as a non-invasive therapeutic procedure to treat solid tumors. However, collateral damage and long sonication times occurring during HIFU ablation procedures limit clinical advancement. In this research, an investigation to determine whether the use of magnetic nano-particles (mNPs) or gold nano-particles (gNPs) could reduce the power required to ablate tissue or, for the same power, reduce the duration of the procedure was performed using invasive and non-invasive modalities. Phantoms containing embedded thermocouples (TCs) and physiologically acceptable concentrations (phi) of mNPs (0%, 0.0047%, and 0.047%) and gNPs (0.0625%, and 0.125%) were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 seconds. It was found that with the 0.047% mNP phi, the power required to obtain a lesion volume of 13 mm^3 could be halved. When the phi of gNPs was doubled from 0.0625% to 0.125%, the temperature rise increased by 80% for a power of 5.2 W. Subsequently, a study was conducted to assess the utility of using gNPs during HIFU procedures, using non-invasive modality in phantoms and in-vivo mouse tumors. Tumors were grown using melanoma tumor cells (B16/F10) subcutaneously on the right flanks of mice (C57Bl/6). Histopathology study was conducted using a cleaved caspase 3 antibody and Hematoxylin and Eosin staining after removing the tumors from the mice. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs phi of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs phi in phantoms. For the power of 15 W, in phantoms, a lesion volume of 0 mm^3, 44.5+/-7 mm^3, and 63.4+/-32 mm^3 was calculated for the gNPs phi of 0%, 0.0625%, and 0.125%, respectively. In tumors, for an acoustic power of 30 W, end-of-sonication temperature rises of 25.4+/-3.8 deg C (0% gNP), 33.6+/-0.1 deg C (0.0625% gNP), and 42.2+/-4.6 deg C (0.125% gNP) were measured. Using cleaved caspase 3 antibody, it was observed that more than 1.5% of nuclei are affected in the case of 0.0625% and 30 W but only 0.01% of nuclei are affected in 0% case. For 30 W and a gNP concentration of 0.125%, a lesion volume of 0.55 mm^3 was obtained, while no lesion was observed without gNP’s. Lastly, a theoretical research to determine the mechanism behind nanoparticle-mediated enhanced energy transfer during HIFU sonication was evaluated. It was observed from theoretical calculation that the phonon layer at the interface of the mNPs and TMM dominates the attenuation for higher (0.047 %) phi. Attenuation due to the viscous drag becomes the dominating mechanism for higher size mNPs (> 1000 nm). At a higher phi (0.047%), it was observed from theoretical calculations that the temperature rise was 25% less for gold nano-particles (gNPs) when compared to mNPs. It can be concluded that mNPs and gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.
Rupak Banerjee, Ph.D (Committee Chair)
Michael Kazmierczak, Ph.D. (Committee Member)
Jay Kim, Ph.D. (Committee Member)
Matthew Myers, Ph.D. (Committee Member)
174 p.
Mechanical Engineering
HIFU; ablation; nanoparticles; tumor; histopathology; lesion

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Citations

  • Devarakonda, S. B. (2018). Enhanced Thermal Ablation of Biomaterials Using High-Intensity Focused Ultrasound (HIFU) Energized Nano-particles [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1544001995977567

    APA Style (7th edition)

  • Devarakonda, Surendra. Enhanced Thermal Ablation of Biomaterials Using High-Intensity Focused Ultrasound (HIFU) Energized Nano-particles. 2018. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1544001995977567.

    MLA Style (8th edition)

  • Devarakonda, Surendra. "Enhanced Thermal Ablation of Biomaterials Using High-Intensity Focused Ultrasound (HIFU) Energized Nano-particles." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1544001995977567

    Chicago Manual of Style (17th edition)

ucin1544001995977567
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This open access ETD is published by University of Cincinnati and OhioLINK.