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Modifying Ultrasound Waveform Parameters to Control, Influence, or Disrupt Cells

Citation

Mittelstein, David Reza (2020) Modifying Ultrasound Waveform Parameters to Control, Influence, or Disrupt Cells. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/71ak-w328. https://resolver.caltech.edu/CaltechTHESIS:05242020-045332969

Abstract

Ultrasound can be focused into deep tissues with millimeter precision to perform non-invasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit non-selective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here we describe an alternative low intensity pulsed ultrasound approach known as “oncotripsy” that leverages the distinct mechanical properties of neoplastic cells to achieve inherent cancer selectivity. We show that when applied at a specific frequency and pulse duration, focused ultrasound selectively disrupts a panel of breast, colon, and leukemia cancer cell models in suspension without significantly damaging healthy immune or red blood cells. Mechanistic experiments reveal that the formation of acoustic standing waves and the emergence of cell-seeded cavitation lead to cytoskeletal disruption, expression of apoptotic markers, and cell death. The inherent selectivity of this low intensity pulsed ultrasound approach offers a potentially safer and thus more broadly applicable alternative to non-selective high intensity ultrasound ablation.

In this dissertation, I describe the oncotripsy theory in its initial formulation, the experimental validation and investigation of testable predictions from that theory, and the refinement of said theory with new experimental evidence. Throughout, I describe how careful modifications to the ultrasound waveform directly can significantly impact how the ultrasound bio-effects control, influence, or disrupt cells in a selective and controlled manner.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Ultrasound, Biophysics, Cancer, LIFU, LIPUS, HIFU, Cavitation, Thermal Ultrasound
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Medical Engineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Gharib, Morteza (co-advisor)
  • Shapiro, Mikhail G. (co-advisor)
Thesis Committee:
  • Colonius, Timothy E. (chair)
  • Gharib, Morteza
  • Shapiro, Mikhail G.
  • Ortiz, Michael
Defense Date:26 February 2020
Funders:
Funding AgencyGrant Number
Caltech Innovation Initiative (CI2) Research Grant.UNSPECIFIED
Amgen-CBEA2017-18, 2018-19
City of Hope Biomedical InitiativeUNSPECIFIED
Record Number:CaltechTHESIS:05242020-045332969
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:05242020-045332969
DOI:10.7907/71ak-w328
Related URLs:
URLURL TypeDescription
https://data.caltech.edu/badge/latestdoi/264968241DOIScripts that simulate cavitating bubbles' amplification of incident ultrasound pressure waves.
https://data.caltech.edu/badge/latestdoi/265404998DOIScripts that allow the user to conduct thermal ultrasound experiments with closed loop control using a PID with anti-windup control system.
https://data.caltech.edu/badge/latestdoi/266413229DOIScripts that allow the user to conduct ultrasound experiments
https://data.caltech.edu/badge/latestdoi/266350789DOISolidworks models that may be useful in designing ultrasound experimental rigs.
https://doi.org/10.1063/1.5128627DOIExperimental oncotripsy paper, adopted to Chapter 3
https://doi.org/10.1098/rspa.2019.0692DOIComputational oncotripsy paper, adopted to Chapter 4
https://doi.org/10.1101/620567DOIGV cavitation paper, adopted to Chapter 5
https://doi.org/10.1101/2020.05.19.101196DOINeurmodulation paper, not discussed
https://doi.org/10.1101/691105DOIGV acoustic radiation force paper, not dicussed
ORCID:
AuthorORCID
Mittelstein, David Reza0000-0001-8747-0483
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13721
Collection:CaltechTHESIS
Deposited By: David Mittelstein
Deposited On:01 Jun 2020 22:06
Last Modified:09 Jun 2020 18:37

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