Inder Raj S. Makin

Correlation of ultrasound-induced hemolysis with cavitation detector output in vitro

A 20-MHz passive acoustic detector was used to quantify the amount of transient acoustic cavitation occurring in a sample exposed to intense pulsed ultrasound. A dilute suspension of human erythrocytes with and without a microbubble echo-contrast agent was exposed in vitro to 500 W/cm2 (SPPA) ultrasound of center frequency 1 MHz and tone burst duration 20, 100, 200, 500 and 1000 microseconds at a pulse repetition frequency of 20 Hz. Inertial cavitation occurring within the sample, as measured by the temporal average of the detector output, correlated well with hemolysis, suggesting that violent bubble collapse is responsible for cell damage. The result also raises the prospect of cavitation monitoring as a possible predictor of adverse bioeffects when echo-contrast agents are used clinically.

Effect of acoustic cavitation on platelets in the presence of an echo-contrast agent

A suspension of human platelets in autologous plasma or buffer solution with and without a microbubble echo-contrast agent was exposed in vitro to 730 W/cm2 (ISPPA) ultrasound pulses of duration 40-160 microseconds at 1 MHz and 20-Hz pulse repetition frequency. Inertial cavitation occurring within the samples was monitored during the exposures and a measure of average cavitational activity was calculated for each 5-min exposure. This quantity, with the other acoustic parameters, accounted for up to 75% of the variation in the destruction of platelets as measured by Coulter counter and 83.5% of the release of bound radiolabel using a multiple-interaction statistical model. When the echo-contrast agent was absent, negligible cavitation occurred and the amount of platelet destruction was statistically indistinguishable from sham (no-ultrasound) exposures. Therefore, microbubble echo-contrast agents may interact with ultrasound to cause platelet lysis through the mechanism of inertial cavitation.

Acoustic and system parameters affecting destruction of ultrasound contrast agents

In order to effectively use ultrasound contrast agents (UCAs), it is necessary to tune the ultrasound scanner parameters to a particular agent or change the characteristics of the UCA to target‐specific applications. Both efforts are being sought by ultrasound manufacturers and pharmaceutical companies. The destruction of UCAs is usually undesirable, although it can sometimes be used advantageously such as in harmonic imaging mode. In the present work, changes in acoustic and system parameters such as frequency, transmitted acoustic pressure, pulse repetition frequency, flow rate, diluting media, concentration, and type of contrast agents were measured at both first and second harmonic. A prototype Doppler system previously described [Chang et al., Ultrasound Med. Biol. 22, 1205–1214 (1996)] has been adapted to carry out these measurements. Results with Albunex show that bubble destruction increases with an increase in flow rate, acoustic pressure, PRF, and decreases with an increase in the concentration ...

Pressure and cavitation measurements of an intra‐arterial angioplasty device

Variation of the acoustic field radiated from a low‐frequency (22.5 kHz) catheterlike angioplasty device in a relatively large (600 L) tank of water was presented earlier [I. R. S. Makin and E. C. Everbach, 2855(A) (1994)]. The normal volume of the human torso or the human limb into which the ultrasonic wire is inserted during therapy cannot be treated, however, as an infinite medium for the 66.6‐mm wavelength (calculated for water) due to the wire source. Therefore the sound field of the device was investigated in a liquid‐filled Plexiglasregistered cylinder (200‐mm diameter, 350‐mm height) to simulate anthropometric dimensions. Measurement of pressures along the axis of the cylinder for the wire source positioned axially at one end of the cylinder shows a marked standing wave pattern even up to an axial range of 250 mm. Such strong standing waves could potentially exist far away from the probe tip in vivo. In addition, the occurrence of cavitation at the tip of the wire was confirmed using a 20‐MHz pass...

Active cavitation detection of microbubble echocontrast agents in blood

Apfel’s active cavitation detector [Roy et al., J. Acoust. Soc. Am. 87, 2451–2458 (1990)] has been improved to allow quantification of microbubble activity in reconstituted human blood. One‐microsecond‐long 20‐MHz tone bursts are scattered from microbubbles undergoing transient cavitation at the focus of a pulsed 1‐MHz transducer. The host medium consists either of human red blood cells suspended in autologous plasma or platelet‐rich plasma, with various concentrations of microbubble‐based echocontrast agent present. The microbubble activity inferred from the backscattered tone bursts is compared to measured bioeffects (hemolysis, platelet aggregation) in order to determine the physical basis for cavitational damage of blood components. Current results as a function of system parameters will be presented. [Work supported by NSF MSS‐9253777.]

Experimental results for transmission of a finite‐amplitude, focused sound beam at a curved interface between two media

Transmission of an intense focused sound beam through two different liquids separated by a curved interface was investigated experimentally. The acoustic field was generated by a 2.25‐MHz tone burst from a focused source of radius 19 mm and focal length 159 mm. Measurements of propagation curves and beam patterns were made using a PVDF needle hydrophone. The source was placed in water, the first liquid, and either lamp oil (cwater/coil=1.08) or a 50% glycerin–water mixture (cwater/cmixture =0.85) was used as the second liquid. Curvature at the interface between the water and the second liquid was controlled by using a thin (≊40 μm) polyether polyurethane membrane. Both concave or convex curvatures, with radii varying from 90 mm to infinity (plane interface), were achieved by varying the hydrostatic pressure between the two liquid chambers. Measurements were compared with theory, presented earlier [Makin, J. Acoust. Soc. Am. 95, 2864(A) (1994)], based on the nonlinear parabolic (KZK) wave equation. Reasona...

Effects of acoustic cavitation on luminescent bacteria

The interaction of intense ultrasound with bacteria has implications for improving fundamental understanding in biology and bioacoustics, as well as providing possible applications in water purification and medicine. An investigation will be presented of the effects of acoustic cavitation on E.coli bacteria that have been genetically engineered to emit visible light when subjected to physical or chemical stress. Genetic cloning techniques allow the placement of the lux gene, derived from luminescent marine microorganisms, at specific locations in bacterial DNA. Each placement location yields light production in proportion to the repair mechanism employed by the bacteria in response to specific kinds of stress (oxidative damage, DNA damage, membrane damage, protein damage, thermal damage, etc.). A 20‐MHz passive acoustic detector [abstract, Huertas et al., 2856 (1994)] was used to quantify cavitational activity when bacteria were exposed to 1‐MHz pulsed ultrasound. By comparing a measure of cavitational ac...

Correlation of cavitation‐induced damage to blood elements with passive acoustic detector output

A 20‐MHz probe transducer placed confocally with a 1‐MHz cavitation transducer was used to detect inertial cavitation in human blood preparations [Huertas et al., J. Acoust. Soc. Am. 95, 2856(A) (1994)]. The preparations included suspensions of red blood cells (RBCs) and platelets in autologous plasma with or without the addition of Albunex (R) microbubble contrast agent. Damage to RBCs and platelets was measured hematologically and correlated with statistical descriptors of the fluctuating voltages from the passive cavitation detector. Good correlations were obtained between the average rms cavitation signal and percent hemolysis of diluted RBCs. In the platelet preparations, detector output paralleled damage as measured both by Coulter counter and by leakage of radiolabeled chromium‐51 through platelet membranes. Advantages and shortcomings of the passive acoustic detection scheme used to predict cavitational damage to blood constituents will be discussed. [Work supported by an NSF PFF.]

Field measurements for an intra‐arterial angioplasty device

Ultrasonic angioplasty devices awaiting FDA approval are being developed for the removal of atheromatous plaque in peripheral and coronary arteries [abstract, O. K. Colliou and E. C. Everbach, J. Acoust. Soc. Am. 93, 2330 (1993)]. This talk presents the results of work in progress on characterizing the acoustic field due to a vibrating ultrasonic catheter wire (MedSonic, Inc., New York), which is a second‐generation device with a titanium spherical tip at its end. Changes in the radiation characteristics of the system operating at 22.2 kHz (cw) will be discussed, based on varying the system parameters. Results will be presented from wires with different ball‐tip diameters, different driver intensity settings, and varying viscosities of damping fluid in the wire sheath. By determining the acoustic field of the device, the probable regions of cavitational activity responsible for the bioeffects observed clinically can be identified. [Work supported by NSF MSS‐9253777.]