Optimizing Acoustic Activation of Phase Change Contrast Agents With the Activation Pressure Matching Method: A Review

Sub-micron phase-change contrast agents consist of a liquid perfluo ocarbon core that can be vaporized by ultrasound (acoustic droplet vaporization) to generate contrast with excellent spatial and temporal control. When these agents, commonly referred to as nanodroplets, are formulated with cores of low boiling-point perfluo ocarbons such as decaflu orobutane and octafluo opropane, they can be activated with low-mechanical index imaging pulses for diagnostic applications. Since the utilization of minimum mechanical index is often desirable to avoid unnecessary biological effects, enabling consistent activation of these agents in an acoustic fiel is a challenge because the energy that must be delivered to achieve the vaporization threshold increases with depth due to attenuation. A novel vaporization approach called Activation Pressure Matching has been developed to deliver the same pressure throughout a fiel of view in order to produce uniform nanodroplet vaporization and to limit the amount of energy that is delivered. In this manuscript, we discuss the application of this method with a Versasonics V1 Research Ultrasound System to modulate the output pressure from an ATL L11–5 transducer. Vaporization-pulse spacing optimization can be used in addition to matching the activation pressure through depth, and we demonstrate the feasibility of this approach both in vivo and in vitro. The use of optimized vaporization parameters increases the amount of time a single bolus of nanodroplets can generate useful contrast and provides consistent image enhancement in vivo. Therefore, APM is a useful technique for those wishing to maximize the efficac of phase change contrast agent while minimizing delivered acoustic energy

Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

Phase-change contrast agents (PCCAs) provide a dynamic platform to approach problems in medical ultrasound (US). Upon US-mediated activation, the liquid core vaporizes and expands to produce a gas bubble ideal for US imaging and therapy. In this study, we demonstrate through high-speed video microscopy and US interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs) exhibit unique acoustic behavior that can be detected and differentiated from standard microbubble contrast agents. Experimental results show that when activated with short pulses PCCAs will over-expand and undergo unforced radial oscillation while settling to a final bubble diameter. The size-dependent oscillation phenomenon generates a unique acoustic signal that can be passively detected in both time and frequency domain using confocal piston transducers with an ‘activate high’ (8 MHz, 2 cycles), ‘listen low’ (1 MHz) scheme. Results show that the magnitude of the acoustic ‘signature’ increases as PFC boiling point decreases. By using a band-limited spectral processing technique, the droplet signals can be isolated from controls and used to build experimental relationships between concentration and vaporization pressure. The techniques shown here may be useful for physical studies as well as development of droplet-specific imaging techniques

Wideband acoustic activation and detection of droplet vaporization events using a capacitive micromachined ultrasonic transducer

An ongoing challenge exists in understanding and optimizing the acoustic droplet vaporization (ADV) process to enhance contrast agent effectiveness for biomedical applications. Acoustic signatures from vaporization events can be identified and differentiated from microbubble or tissue signals based on their frequency content. The present study exploited the wide bandwidth of a 128-element capacitive micromachined ultrasonic transducer (CMUT) array for activation (8 MHz) and real-time imaging (1 MHz) of ADV events from droplets circulating in a tube. Compared to a commercial piezoelectric probe, the CMUT array provides a substantial increase of the contrast-to-noise ratio

Adaptive windowing in contrast-enhanced intravascular ultrasound imaging

Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200 µm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2 dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2 dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium

Micromorphology and Site Formation at Hohle Fels Cave, Schwabian Jura, Germany

Die Höhle Hohle Fels liegt auf der Schwäbischen Alb bei Schelklingen und beinhaltet eine stratigraphische Folge, die mindestens 36.000 Jahre zurück geht und Aurignacien-, Gravettien- und Magdalénien-Fundschichten beinhaltet. Die Sedimente vom Hohle Fels wurden mit mikromorphologischen Analysen in Kombination mit Elektronmikroprobe und FTIR-Analysen untersucht. Die Ergebnisse zeigen, dass die Sedimente aus dem inneren Bereich der Höhle stammen und das die feine Matrix in Zusammenhang mit der Nutzung der Höhle durch Bären eine starke Phosphatenanreicherung erlebt hat. Mikrostrukturen belegen kalte und feuchte klimatische Phasen, charakterisiert durch Kryoturbation und Eislinsen. Diese Merkmale sind in den Gravettien- und Magdalénien-Schichten stärker entwickelt und sprechen für kühle Bedingungen während dieser Perioden. Während des letzten Kältemaximums fehlen Hinweise für die Nutzung der Höhle durch Menschen und Höhlenbären. Diese Beobachtungen können als Grundlage dienen, um Hypothesen über das Paläoklima und über menschliches Verhalten im Paläolithikum, die anhand botanischer, faunistischer und archäologischer Daten entwickelt wurden, zu prüfen. Einige der Methoden dieser Untersuchungen wurden zum ersten Mal in den Höhlen der Schwäbischen Alb eingesetzt und lieferten viel versprechende Einblicke in die Archäologie und die naturhistorische Entwicklung der Region.researc

Advances in Molecular Imaging with Ultrasound

Ultrasound imaging has long demonstrated utility in the study and measurement of anatomic features and noninvasive observation of blood flow. Within the last decade, advances in molecular biology and contrast agents have allowed researchers to use ultrasound to detect changes in the expression of molecular markers on the vascular endothelium and other intravascular targets. This new technology, referred to as ultrasonic molecular imaging, is still in its infancy. However, in preclinical studies, ultrasonic molecular imaging has shown promise in assessing angiogenesis, inflammation, and thrombus. In this review, we discuss recent advances in microbubble-type contrast agent development, ultrasound technology, and signal processing strategies that have the potential to substantially improve the capabilities and utility of ultrasonic molecular imaging