Access Type

Open Access Dissertation

Date of Award

January 2013

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

Michele J. Grimm

Second Advisor

Thilo Hoelscher

Abstract

Worldwide, stroke is the second most common cause of death. Ischemic stroke remains accountable for the majority of the 20 million devastating stroke events occurring globally each year. Use of transcranial focused ultrasound (FUS) for sonothrombolysis is a new research field for ischemic stroke treatment. If shown to be effective, FUS sonothrombolysis could become a widely available treatment option for the majority of the stroke sufferers that do not qualify or do not have access to current thrombolytic treatment options, such as tPA or neurointerventional methods.

The current study was an in vitro transcranial FUS headsystem investigation for the potential treatment of stroke. It was segmented and approached as four progressively building, specific objectives that were developed to collectively answer the investigational question: is focused ultrasound effective for transcranial sonothrombolysis in stroke?

(1) Determine the technique feasibility of a FUS system for transcranial sonothrombolysis

(2) Perform a parameter optimization for the FUS system for effective sonothrombolysis by varying duty cycle and pulse width settings

(3) Characterize the acoustic field produced by the transcranial FUS and determine how it is affected by the skull

(4) Determine how sonothrombolysis efficacy and potential clot fragmentation are impacted by varying the FUS intensity

The observed, novel in vitro experiences using this new technology are very encouraging. From the four sets of experiments, we have learned that: 1) FUS sonothrombolysis is feasible in an in vitro transcranial flow model; 2) FUS operating parameters such as duty cycle and pulse width can be varied for optimized clot lysis efficacy; 3) transcranial sonothrombolysis efficacy is also dependent on individual skull bone characteristics; and 4) clot lysis depends on the acoustic output power of the FUS system as it relates to effective clot breakdown and potential clot fragments.

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