Shunji Gao

Microbubble cavitation imaging

Ultrasound cavitation of microbubble contrast agents has a potential for therapeutic applications such as sonothrombolysis (STL) in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (moderate oscillations, stable cavitation, and inertial cavitation) and activity level in and around a treatment area. Acoustic passive cavitation detectors (PCDs) have been used to this end but do not provide spatial information. This paper presents a prototype of a 2-D cavitation imager capable of producing images of the dominant cavitation state and activity level in a region of interest. Similar to PCDs, the cavitation imaging described here is based on the spectral analysis of the acoustic signal radiated by the cavitating microbubbles: ultraharmonics of the excitation frequency indicate stable cavitation, whereas elevated noise bands indicate inertial cavitation; the absence of both indicates moderate oscillations. The prototype system is a modified commercially available ultrasound scanner with a sector imaging probe. The lateral resolution of the system is 1.5 mm at a focal depth of 3 cm, and the axial resolution is 3 cm for a therapy pulse length of 20 μs. The maximum frame rate of the prototype is 2 Hz. The system has been used for assessing and mapping the relative importance of the different cavitation states of a microbubble contrast agent. In vitro (tissue-mimicking flow phantom) and in vivo (heart, liver, and brain of two swine) results for cavitation states and their changes as a function of acoustic amplitude are presented.

Investigation of effectiveness of microbubble stable cavitation in thrombolysis

Ultrasound and intravenous microbubbles have been used in recanalizing intravascular thrombi which cause ischemic stroke, myocardial infarction, and other vascular thrombo-embolic events. In previous studies, inertial cavitation (IC) produced by high mechanical index (MI) ultrasound has been shown to be effective in dissolving acute thrombi. However, IC is more likely to cause adverse bioeffects than stable cavitation (SC). This study indicates that SC induced by intermediate MI ultrasound (1.6 MHz, 0.35 MI, 50 cycles) is as effective for acute thrombus dissolution as IC by high MI ultrasound (1.6 MHz, 1.1 MI, 2.5 cycles).

Investigation of image-guided sonothrombolysis in a porcine acute ischemic stroke model

Image-guided sonothrombolysis was prototyped on a modified ultrasound imaging system iE33 and further evaluated using a porcine acute ischemic stroke model. After 20 to 40 minute sonothrombolysis treatment with systemic infusion of Definity microbubbles, contrast reperfusion and arterial recanalization were observed on low MI ultrasound contrast imaging and X-ray based angiography, respectively. The study indicates that a modified diagnostic imaging system can be utilized with systemic microbubble infusion to rapidly restore cerebral blood flow in acute ischemic stroke.

Image-guided sonothrombolysis in a stroke model with a cavitation delivery and monitoring system

Microbubbles (MB) and ultrasound (US) can dissolve intra-arterial thrombi. In order to reproducibly deliver the correct cavitation dose and ensure treatment efficacy and safety, we designed a therapeutic US mode with cavitation monitoring. Therapy delivery and recording of the MB signal are achieved with a sector imaging probe. Monitoring is achieved by spectrally analyzing the MB signal: ultraharmonics are a marker of stable cavitation (SC) and broadband noise characterizes inertial cavitation (IC). We used the system in a pig model. Thrombotic occlusions were created by injecting 4-hour old clots bilaterally into the internal carotids. Forty pigs were randomized to either 2.4 MI, 5 μs pulses with MBs; 1.7 MI, 20 μs pulses with MBs; and 2.4 MI, 5 μs pulses without MBs. Angiographic recanalization rates were compared. Cavitation as a function of MI was estimated in vivo. Dominant SC started at an applied MI of 0.6 (0.3MI in situ after derating by skull attenuation). Dominant IC was estimated to start at a...

Transcranial threshold of inertial cavitation induced by diagnostic ultrasound and microbubbles

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.