Biomedical subjects

Michiel Postema

Publications and source records attributed to Michiel Postema.

7 recordsLinked to original sources

PubMed2006

Nitric oxide delivery by ultrasonic cracking: some limitations.

Nitric oxide (NO) has been implicated in smooth muscle relaxation. Its use has been widespread in cardiology. Due to the effective scavenging of NO by hemoglobin, however, the drug has to be applied locally or in large quantities, to have the effect desired. We propose the use of encapsulated microbubbles that act as a vehicle to carry the gas to a region of interest. By applying a burst of high-amplitude ultrasound, the shell encapsulating the gas can be cracked. Consequently, the gas is released upon which its dissolution and diffusion begins. This process is generally referred to as (ultra)sonic cracking. To test if the quantities of released gas are high enough to allow for NO-delivery in small vessels (ø<200 microm), we analyzed high-speed optical recordings of insonified stiff-shelled microbubbles. These microbubbles were subjected to ultrasonic cracking using 0.5 or 1.7 MHz ultrasound with mechanical index MI>0.6. The mean quantity released from a single microbubble is 1.7 fmol. This is already more than the NO production of a 1mm long vessel with a 50 microm diameter during 100 ms. However, we simulated that the dissolution time of typical released NO microbubbles is equal to the half-life time of NO in whole blood due to scavenging by hemoglobin (1.8 ms), but much smaller than the extravascular half-life time of NO (>90 ms). We conclude that ultrasonic cracking can only be a successful means for nitric oxide delivery, if the gas is released in or near the red blood cell-free plasma next to the endothelium. A complicating factor in the in vivo situation is the variation in blood pressure. Although our simulations and acoustic measurements demonstrate that the dissolution speed of free gas increases with the hydrostatic pressure, the in vitro acoustic amplitudes suggest that the number of released microbubbles decreases at higher hydrostatic pressures. This indicates that ultrasonic cracking mostly occurs during the expansion phase.

Capsules↗

PubMed2006

Bubble dynamics involved in ultrasonic imaging.

In clinical ultrasound, blood cells cannot be differentiated from surrounding tissue, due to the low acoustic impedance difference between blood cells and their surroundings. Resonant gas bubbles introduced in the bloodstream are ideal markers, if rapid dissolution can be prevented. Ultrasound contrast agents consist of microscopically small bubbles encapsulated by an elastic shell. These microbubbles oscillate upon ultrasound insonification. Microbubbles with thin lipid shells have demonstrated highly nonlinear behavior. To enhance diagnostic ultrasound imaging techniques and to explore therapeutic applications, these medical microbubbles have been modeled. Several detection techniques have been proposed to improve the detectability of the microbubbles. A new generation of contrast agents, with special targeting ligands attached to the shells, may assist the imaging of nonphysical properties of target tissue. Owing to microbubble-based contrast agents, ultrasound is becoming an even more important technique in clinical diagnostics.

Blood Cells↗

PubMed2005

Ultrasound-induced gas release from contrast agent microbubbles.

We investigated gas release from two hardshelled ultrasound contrast agents by subjecting them to high-mechanical index (MI) ultrasound and simultaneously capturing high-speed photographs. At an insonifying frequency of 1.7 MHz, a larger percentage of contrast bubbles is seen to crack than at 0.5 MHz. Most of the released gas bubbles have equilibrium diameters between 1.25 and 1.75 microm. Their disappearance was observed optically. Free gas bubbles have equilibrium diameters smaller than the bubbles from which they have been released. Coalescence may account for the long dissolution times acoustically observed and published in previous studies. After sonic cracking, the cracked bubbles stay acoustically active.

Contrast Media↗

PubMed2005

High-speed photography during ultrasound illustrates potential therapeutic applications of microbubbles.

Ultrasound contrast agents consist of microscopically small encapsulated bubbles that oscillate upon insonification. To enhance diagnostic ultrasound imaging techniques and to explore therapeutic applications, these medical microbubbles have been studied with the aid of high-speed photography. We filmed medical microbubbles at higher frame rates than the ultrasonic frequency transmitted. Microbubbles with thin lipid shells have been observed to act as microsyringes during one single ultrasonic cycle. This jetting phenomenon presumably causes sonoporation. Furthermore, we observed that the gas content can be forced out of albumin-encapsulated microbubbles. These free bubbles have been observed to jet, too. It is concluded that microbubbles might act as a vehicle to carry a drug in gas phase to a region of interest, where it has to be released by diagnostic ultrasound. This opens up a whole new area of potential applications of diagnostic ultrasound related to targeted imaging and therapeutic delivery of drugs such as nitric oxide.

Biophysical Phenomena↗

PubMed2004

Noninvasive microbubble-based pressure measurements: a simulation study.

This paper describes a noninvasive method to measure local hydrostatic pressures in fluid filled cavities. The method is based on the disappearance time of a gas bubble, as the disappearance time is related to the hydrostatic pressure. When a bubble shrinks, its response to ultrasound changes. From this response, the disappearance time, and with it the hydrostatic pressure, can be determined. We investigated the applicability of the gases Ar, C(3)F(8), Kr, N(2), Ne, and SF(6), based on their diffusive properties. For pressure measurements with a limited duration, e.g. 150 ms, Kr and Ar bubbles are most suitable, since they are most sensitive to pressure change. If there is also a limitation to bubble size, e.g. a maximum diameter of 6 microm, SF(6) is most suitable. We present improvements of a method that correlates the duration of the decay of the fundamental ultrasound response to the hydrostatic overpressure. We propose to correlate the duration until subharmonic occurrence in combination with its decay, to hydrostatic overpressure, since the subharmonic decays more rapidly than the fundamental response. For a dissolving Ar gas bubble with an initial diameter of 14 microm, the overpressure can be determined 4 times as precise from the decay of the subharmonic response as from the decay of the fundamental response. Overpressures as small as 11 mmHg may be discriminated with this method.

Contrast Media↗

PubMed2004

Ultrasound-induced encapsulated microbubble phenomena.

When encapsulated microbubbles are subjected to high-amplitude ultrasound, the following phenomena have been reported: oscillation, translation, coalescence, fragmentation, sonic cracking and jetting. In this paper, we explain these phenomena, based on theories that were validated for relatively big, free (not encapsulated) gas bubbles. These theories are compared with high-speed optical observations of insonified contrast agent microbubbles. Furthermore, the potential clinical applications of the bubble-ultrasound interaction are explored. We conclude that most of the results obtained are consistent with free gas bubble theory. Similar to cavitation theory, the number of fragments after bubble fission is in agreement with the dominant spherical harmonic oscillation mode. Remarkable are our observations of jetting through contrast agent microbubbles. The pressure at the tip of a jet is high enough to penetrate any human cell. Hence, liquid jets may act as remote-controlled microsyringes, delivering a drug to a region-of-interest. Encapsulated microbubbles have (potential) clinical applications in both diagnostics and therapeutics.

Acoustics↗

PubMed2004

Ultrasound-induced microbubble coalescence.

We studied the interaction of ultrasound contrast agent bubbles coated with a layer of lipids, driven by 0.5 MHz ultrasound. High-speed photography on the submicrosecond timescale reveals that some bubbles bounce off each other, while others show very fast coalescence during bubble expansion. This fast coalescence cannot be explained by dissipation-limited film drainage rates. We conclude that the lipid shell ruptures upon expansion, exposing clean free bubble interfaces that support plug flow profiles in the film and inertia-limited drainage whose time scales match those of the observed coalescence.

Contrast Media↗