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Background: Inertial cavitation may cause hazardous bioeffects whileusing ultrasound and microbubble mediated thrombolysis. The purposeof this study was to investigate the influence of ultrasound pulselength and temporal bone on inertial cavitation thresholds within the brain utilizing transtemporal imaging transducers. Methods: A pig temporal bone overlaid with muscle tissue was placed over silastictubing containing a dilute microbubble infusion (0.5% Definity) within Phosphate Buffered Saline at 37 °C. A 1.6 MHz Philips iE33 two-dimensional probe (S5-1) imaged at incremental peak negative pressures. Broadband noise signals were recorded to characterize inertial cavitation using two 20 MHz passive cavitaion detectors (PCD). Backscattered RF signals were recorded by iE33. Results: About half of the acoustic pressure was attenuated by the temporal bone. Peak-negative-pressure thresholds of inertial cavitation were approximately equal to 0.51 and 0.31 MPa, 0.46 and 0.29 MPa for 5 and 20 microsecondspulse durations with and without bone, respectively. RF signals from the S5-1 correlated with inertial cavitation thresholds from the PCD. Conclusion: The threshold of inertial cavitation is influencedby ultrasound pulse length and temporal bone. RF signals can be used to characterize cavitation behavior for bone attenuation estimation and compensation.

Ultrasound cavitation of microbubble contrast agents has a potentialfor therapeutic applications, including sonothrombolysis in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (e.g. stable versus inertial forms of cavitation) and intensity in and around a treatment area. Acoustic Passive Cavitation Detectors (PCDs) have been used but lack spatial information. This paper presents a prototype ofa 2D cavitation imager capable of producing images of the dominantcavitation state and intensity in a region of interest at a frame rate of 0.6Hz. The system is based on a commercial ultrasound scannerand imaging probe (iE33 scanner with S5-1 probe, Philips). Cavitation imaging is based on the spectral analysis of acoustic signal radiated by the cavitating microbubbles: ultraharmonics of the excitationfrequency indicate stable cavitation, while noise bands indicate inertial cavitation. The system demonstrates the capability to robustly identify stable and inertial cavitation thresholds of Definity microbubbles (Lantheus) in a vessel phantom through 3 ex-vivo human temporal bones, as well as to spatially discriminate the location of cavitation activities.

Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA to liver in conjunction with microbubbles may provide a potential treatment for GSDIa patients. As the success of USMD treatmentsis largely dependent on the accessibility of the targeted tissue bythe focused ultrasound beam, this study presents a quantitative approach to determine the acoustically accessible liver volume in GSDIapatients. Models of focused ultrasound beam profiles for transducers of varying aperture and focal lengths were applied to abdomen models reconstructed from suitable CT and MRI images. Transducer manipulations (simulating USMD treatment procedures) were implemented via transducer translations and 2D rotations with the intent of targetingand exposing the entire liver to ultrasound. Results indicate thatacoustically accessible liver volumes can be as large as 60% of theentire liver volume for GSDIa patients and on average 3 times largercompared to a normal group due to GSDIa patients’ increased liver size. Detailed descriptions of the evaluation algorithm, transducer-and abdomen models will be presented, together with implications forUSMD treatments of GSDIa patients and transducer designs for USMD applications.