Ultrasound-induced Mild Hyperthermia for Controlled Tissue Heating and Drug Delivery PDF Download

Author: Chun-Yen Lai
Publisher:
ISBN: 9781303153822
Category :
Languages : en
Pages :

Get Book Here

Book Description
Ultrasound-induced mild hyperthermia is a promising cancer therapy strategy as high duty cycle ultrasound waves are utilized to induce a temperature of -42°C to increase cell membrane permeability and drug delivery efficiency. Ultrasound is noninvasive, provides spatial selectivity, and is free of ionizing radiation, thus localized thermal therapy is accomplished without concerns occurring in surgery, radiotherapy or chemotherapy. Tight control of ultrasound-induced mild hyperthermia is crucial in order to maximize therapeutic effect in a local area while minimizing unwanted thermal effects on the surrounding healthy tissue. In this dissertation, an advanced ultrasound mild hyperthermia system is established on a clinical scanner, to which modified software, a custom transducer, and an external temperature feedback system are integrated to perform a controlled thermal therapy. The motivation of this study is to develop an image-guided drug delivery system using ultrasound-induced mild hyperthermia. A dual-mode linear array transducer incorporating two 1.54-MHz therapeutic arrays and one 5.5-MHz imaging array was used in the study, in which single-beam and scanned-beam insonation were investigated and simulated. Agarose-based phantom models were established and functionalized for purposes, such as thermometry, visualization of drug release, and phantom design. Low temperature sensitive liposomes (LTSLs) were synthesized to encapsulate near-infrared fluorescence dye for drug release examination in various environments (phantom or solution), to which a simulation tool was developed to simulate drug delivery. An algorithm for ultrasound thermometry was developed in this study, facilitating thermal dose control in a broad region of interest. An approach to achieve more accurate ultrasound thermometry was studied by characterizing the tissue dependent thermal strain parameter and associating the parameter with computed tomography (CT) radiodensity. Finally, ultrasound-induced mild hyperthermia and cancer drugs were combined to perform tumor therapy on a mouse bearing breast cancer xenografts, and therapeutic effects and systemic toxicity were analyzed. Overall, three contributions are described in this work. First, the development of ultrasound-induced mild hyperthermia provides the capability to apply thermal therapy both in vitro and in vivo. Single-beam and scanned-beam insonation were characterized for delivering energy along a single line-of-sight and within a defined region of interest, respectively, allowing flexible planning of tumor treatment. The combination of scanned-beam insonation and drug delivery in a tumor model demonstrated therapeutic efficacy, while systemic toxicity and recurrence of tumors were not observed. Second, tissue-mimicking phantoms were created to test delivery. By incorporating LTSLs in the phantom, the three-dimensional (3-D) drug release profile was visualized using an optical imaging system. The simulation tool developed based on the finite-difference time-domain (FDTD) algorithm was validated by the phantom model and thus provided the ability to predict the kinetics of drug release. Third, the algorithm developed for ultrasound thermometry was shown to be practical for in vivo use. Using phantoms consisting of varied fat concentrations, the relationship between the tissue dependent thermal strain parameter and CT radiodensity was determined. Taken together, the contributions facilitate creation of a novel integrated ultrasound system capable of modern cancer therapy.