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 mu s. 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

Medical Diagnostic Ultrasound

As early as 250 BCE, captains of ancient Greek ships would drop lead weights overboard to provide an estimate of water depth. They would count until those “sounders” produced an audible thud and in that way measure the propagation time of the falling weight. Even though the practice has given way to other technologies for sounding, one still hears the phrase “to sound something out.” In the 17th century, Isaac Newton became fascinated with sound propagation and was one of the first to describe relationships between the speed of sound and measurable properties of the propagation medium, such as density and pressure. Section 8 of Book 2 of the Principia, for example, is devoted to “the motion propagated through fluids” and includes the proposition that the sound speed is given by the square root of the ratio of the “elastic force” to the density of the medium

Effects Of Attenuation And Thrombus Age On The Success Of Ultrasound And Microbubble-Mediated Thrombus Dissolution

The purpose of this study was to examine the effects of applied mechanical index, incident angle, attenuation and thrombus age on the ability of 2-D vs. 3-D diagnostic ultrasound and microbubbles to dissolve thrombi. A total of 180 occlusive porcine arterial thrombi of varying age (3 or 6 h) were examined in a flow system. A tissue-mimicking phantom of varying thickness (5 to 10 cm) was placed over the thrombosed vessel and the 2-D or 3-D diagnostic transducer aligned with the thrombosed vessel using a positioning system. Diluted lipid-encapsulated microbubbles were infused during ultrasound application. Percent thrombus dissolution (%TD) was calculated by comparison of clot mass before and after treatment. Both 2-D and 3-D-guided ultrasound increased %TD compared with microbubbles alone, but %TD achieved with 6-h-old thrombi was significantly less than 3-h-old thrombi. Thrombus dissolution was achieved at 10 cm tissue-mimicking depths, even without inertial cavitation. In conclusion, diagnostic 2-D or 3-D ultrasound can dissolve thrombi with intravenous nontargeted microbubbles, even at tissue attenuation distances of up to 10 cm. This treatment modality is less effective, however, for older aged thrombi. (E-mail: [email protected]) (C) 2011 World Federation for Ultrasound in Medicine & Biology

Characterization Of Individual Submicron Perfluorocarbon Gas Bubbles By Ultrasonic Backscatter

Measurements were undertaken to determine the unknown microbubble-size distribution of a dodecafluoropentane (DDFP) emulsion consisting of in surfactant-stabilized water. The acoustic backscatter of 2-microsecond-duration tonebursts of 30-MHz focused ultrasound was measured from the emulsion as it moved in a coaxial flow. Calibration for the system was accomplished using 3-μm-radius polystyrene spheres, using a linear scattering model and literature values for polystyrene. Applying viscous linear scattering theory to the backscatter data from individual DDFP bubbles allowed inversion of the radius–backscatter relation. A mean microbubble radius of 130 nm was inferred for the DDFP population. © 2005 Acoustical Society of America

A Corrected Mixture Law For B/A

A derivation is presented that corrects an expression for the effective acoustic nonlinearity parameter of a mixture of immiscible liquids. The derivation is based upon a mass fraction, rather than volume fraction, formulation

Diagnostic Ultrasound Induced Inertial Cavitation To Non-Invasively Restore Coronary And Microvascular Flow In Acute Myocardial Infarction

Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery. Pigs were then randomized to either a) 1/2 dose tissue plasminogen activator (0.5 mg/kg) alone; or same dose plasminogen activator and an intravenous microbubble infusion with either b) guided high mechanical index short pulse (2.0 MI; 5 usec) therapeutic ultrasound impulses; or c) guided 1.0 mechanical index long pulse (20 usec) impulses. Passive cavitation detectors indicated the high mechanical index impulses (both long and short pulse duration) induced inertial cavitation within the microvasculature. Epicardial recanalization rates following randomized treatments were highest in pigs treated with the long pulse duration therapeutic impulses (83% versus 59% for short pulse, and 49% for tissue plasminogen activator alone; p \u3c 0.05). Even without epicardial recanalization, however, early microvascular recovery occurred with both short and long pulse therapeutic impulses (p \u3c 0.005 compared to tissue plasminogen activator alone), and wall thickening improved within the risk area only in pigs treated with ultrasound and microbubbles. We conclude that although short pulse duration guided therapeutic impulses from a diagnostic transducer transiently improve microvascular flow, long pulse duration therapeutic impulses produce sustained epicardial and microvascular re-flow in acute myocardial infarction

Improved Sonothrombolysis From A Modified Diagnostic Transducer Delivering Impulses Containing A Longer Pulse Duration

Although guided high-mechanical-index (MI) impulses from a diagnostic ultrasound transducer have been used in preclinical studies to dissolve coronary arterial and microvascular thrombi in the presence of intravenously infused microbubbles, it is possible that pulse durations (PDs) longer than that used for diagnostic imaging may further improve the effectiveness of this approach. By use of an established in vitro model flow system, a total of 90 occlusive porcine arterial thrombi (thrombus age: 3-4 h) within a vascular mimicking system were randomized to 10-min treatments with two different PDs (5 and 20 mu s) using a Philips S5-1 transducer (1.6-MHz center frequency) at a range of MIs (from 0.2 to 1.4). All impulses were delivered in an intermittent fashion to permit microbubble replenishment within the thrombosed vessel. Diluted lipid-encapsulated microbubbles (0.5% Definity) were infused during the entire treatment period. A tissue-mimicking phantom 5 cm thick was placed between the transducer and thrombosed vessel to mimic transthoracic attenuation. Two 20-MHz passive cavitation detection systems were placed confocal to the insonified vessel to assess for inertial cavitational activity. Percentage thrombus dissolution was calculated by weighing the thrombi before and after each treatment. Percentage thrombus dissolution was significantly higher with a 20-mu s PD already at the 0.2 and 0.4 MI therapeutic impulses (54 +/- 12% vs. 33 +/- 17% and 54 +/- 22% vs. 34 +/- 17%, p \u3c 0.05 compared with the 5-mu s PD group, respectively), and where passive cavitation detection systems detected only low intensities of inertial cavitation. At higher MI settings and 20-mu s PDs, percentage thrombus dissolution decreased most likely from high-intensity cavitation shielding of the thrombus. Slightly prolonging the PD on a diagnostic transducer improves the degree of sonothrombolysis that can be achieved without fibrinolytic agents at a lower mechanical index. (E-mail: [email protected]) (c) 2014 World Federation for Ultrasound in Medicine & Biology

Diagnostic Ultrasound High Mechanical Index Impulses Restore Microvascular Flow In Peripheral Arterial Thromboembolism

We sought to explore mechanistically how intermittent high-mechanical-index (MI) diagnostic ultrasound impulses restore microvascular flow. Thrombotic microvascular obstruction was created in the rat hindlimb muscle of 36 rats. A diagnostic transducer confirmed occlusion with low-MI imaging during an intravenous microbubble infusion. This same transducer was used to intermittently apply ultrasound with an MI that produced stable or inertial cavitation (IC) for 10 min through a tissue-mimicking phantom. A nitric oxide inhibitor, L-Nω-nitroarginine methyl ester (L-NAME), was pre-administered to six rats. Plateau microvascular contrast intensity quantified skeletal microvascular blood volume, and postmortem staining was used to detect perivascular hemorrhage. Intermittent IC impulses produced the greatest recovery of microvascular blood volume (p \u3c 0.0001, analysis of variance). Nitric oxide inhibition did not affect the skeletal microvascular blood volume improvement, but did result in more perivascular hemorrhage. IC inducing pulses from a diagnostic transducer can reverse microvascular obstruction after acute arterial thromboembolism. Nitric oxide may prevent unwanted bio-effects of these IC pulses

Noninvasive, Transient and Selective Blood-Brain Barrier Opening in Non-Human Primates In Vivo

The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent central nervous system (CNS) disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. For the first time, the feasibility of transcranial ME-FUS BBB opening in non-human primates is demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (customized 4–5 µm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage