Medical Bubbles
Creators: name: Postema, Michiel
Publisher: name: Zenodo
Year: 2004
Subjects: ultrasound
microbubbles
coalescence
ultrasound contrast agent
high-speed photography

description: PhD thesis Abstract As a result of investigations based on acoustic imaging methods, the use of ultrasound contrast agents are becoming widespread in clinical diag- nostics. Since the acoustic interrogation of an agent takes place on an ensemble of bubbles, however, the contribution of an individual contrast agent microbubble to the acoustic response cannot be predicted. There- fore, the development of more sophisticated detection techniques, and the research on therapeutic applications of ultrasound contrast agents have to be based on other investigation methods, such as high-speed optical imag- ing. In this thesis, we made use of fast-framing camera systems to ob- serve dynamic behavior of individual microbubbles subjected to ultra- sound. Multiple frames were captured during a single ultrasonic cycle. Previous studies made use of (one-dimensional) streak images, or frames that covered multiple ultrasonic cycles. Most of the observed phenomena described in this thesis occur within one ultrasonic cycle. The pictures on which these descriptions were based are asymmetric. Hence, the applicability of streak imaging and slower- than-sound framing in predicting microbubble behavior is very limited. To account for the presence of a shell encapsulating the gas microbub- ble, the physical properties shell stiffness and shell friction have been ac- counted for in models describing microbubble oscillation. These proper- ties have been measured for ensembles of ultrasound contrast agent mi- crobubbles. From our results, however, it is suggested that the shell prop- erties may differ between individual bubbles, because optically identical bubbles reveal different oscillating behavior. The presence of a shell appears to be less of interest for ultrasound contrast agent microbubble phenomena observed at high acoustic pres- sures: The physical mechanisms of microbubble coalescence, fragmenta- tion, translation, and jetting are comparable to those of free gas bubbles in the millimeter range. Because of the fast-framing, we are the first to notice repeated coalescence and fragmentation. Irregular shapes of insonified bubbles were previously interpreted and published in literature as modes of shape instability of a single bubble. However, these shapes may also be accounted for by coalescence of bubbles or bubble fragments. We investigated the influence of the lipid shell on the coalescence by computing the film drainage for immobile bubble surfaces resulting in a laminar flow, and for mobile bubbles surfaces resulting in a plug flow. The coalescence of lipid-encapsulated microbubbles appeared to be unim- peded by shells. Previously, release of gas from encapsulated microbubbles had been assumed from acoustical measurements. We demonstrated such release from encapsulated microbubbles with a rigid albumin shell during insoni- fication. After this so-called ‘sonic cracking’, the free gas dissolves in the surrounding fluid. Although the mechanism of sonic cracking is not yet fully understood, the release of gas from encapsulations may find an ap- plication in noninvasive pressure measurements. Determining overpressures is feasible in vivo from the decay of the fun- damental acoustic response from diffusing released air bubbles. Pressure differences of 50mmHg can be distinguished. In medical diagnostics a resolution lower than 50 mmHg is desirable. To improve the sensitivity of the measurement approach mentioned above, gases other than air might be used. Furthermore, subharmonics may be utilized as a marker for half resonant bubble size, since the subharmonic response is more sensitive to bubble size change than the fundamental. The phenomena observed have potential clinical applications in imaging, pressure measurements, tumor detection, permeabilization, lysis, targeting, and drug delivery.
description: Summary in Dutch
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