Peritoneal adhesions are bands of fibrous tissue that can bind adjacent tissue together and have a high probability of occurrence after a patient undergoes abdominal surgery. The development of adhesions can be detrimental as they can cause intestinal constriction or obstruction, organ displacement, infertility, chronic pain, and in severe cases, even death. Currently, there is no way of detecting adhesions in the body using clinically approved imaging modalities and the standard of care is to perform a controversial second surgery to treat adhesions that can cause more adhesions to form. Therefore, there is a critical need to find new ways of detecting and treating adhesions non-invasively. The larger, overarching project that this thesis is part of aims to fabricate a targeted microbubble that acts as a theranostic agent, which can detect and treat nascent adhesions when exposed to ultrasound.Towards this aim the goals of this thesis are to: 1) characterize the mechanical properties (shell stiffness and shell viscosity) of the microbubble targeting shell that contribute to the microbubble’s response to ultrasound; 2) determine the inertial cavitation threshold, since inertial response will likely be needed in order to break up early-stage adhesions, 3) provide feedback to the larger project to optimize microbubble design and fabrication. The objective of providing feedback is to find a balance between microbubble response to ultrasound and stability under storage and deployment that enables in vivo application. These three goals were achieved by a combination of in vitro experiments and computational modeling of bubble dynamics using the modified linearized Rayleigh- Plesset equation that can predict the dynamics of bubbles with a viscoelastic shell. The results show that inference of shell properties from acoustic transmission experiments shows a strong sensitivity to the microbubble size distribution. If the size distribution is sufficiently well known, then the results indicate that candidate lipid- shelled bubbles possess moderate (∼ 1.4 MPa) shell stiffness and moderate (∼ 0.05 Pa-s) shell viscosity, yielding only modestly resonant bubbles. Counter-intuitively, the results show that even non-resonant bubbles can exhibit a peaked transmission/attenuation frequency response. The inertial cavitation threshold for candidate lipid- shelled bubbles at 1.1 MHz was approximately 2 MPa for low-duty-cycle tone bursts. The results indicate that the candidate lipid shell fabrication technique will produce bubbles that are both sufficiently responsive to provide contrast imaging under diagnostic ultrasound while also requiring a relatively low therapeutic pressure for inertial cavitation lysis. Perhaps the most important feedback to the bubble design and fabrication is the requirement of independent and well-resolved microbubble size distributions. / 2026-01-17T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47940 |
| Date | 18 January 2024 |
| Creators | Doheny, Victoria Valeria |
| Contributors | Holt, R. Glynn, Grace, Sheryl M. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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