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Lawrence A Crum

Publications and source records attributed to Lawrence A Crum.

33 records · Page 2Linked to original sources

Dual-pulse lithotripter accelerates stone fragmentation and reduces cell lysis in vitro.

Lithotripsy is a common effective treatment for kidney stones. However, focal volumes are often larger than stones, and surrounding tissue is often injured. Our goal was to test in vitro a new lithotripter consisting of two opposing, confocal and simultaneously triggered electrohydraulic sources. The pulses superimpose at the common focus, resulting in pressure doubling and enhanced cavitation growth in a localized, approximately 1-cm wide volume. Model gypsum stones and human erythrocytes were exposed to dual pulses or single pulses. At the focus, model stones treated with 100 dual pulses at a charging voltage of 15 kV broke into 8 times the number of fragments as stones treated with 200 single pulses at 18 kV. At axial positions 2 and 4 cm away from the focus, lysis of erythrocytes was reduced or equivalent for dual pulses vs. single pulses. Hence, in half the time, dual pulses increased comminution at the focus without increasing injury in surrounding regions.

Erythrocytes↗

Polyacrylamide gel as an acoustic coupling medium for focused ultrasound therapy.

A hydrogel acoustic coupling medium was investigated as a practical alternative to water for clinical applications of focused ultrasound (US) therapy. Material characterization and functional testing of polyacrylamide gel couplers were performed. Acoustic, bulk and thermal properties were measured. Conical couplers were designed and fabricated to fit a 3.5-MHz, spherically concave transducer for functional tests, including Schlieren imaging, power efficiency measurements and in vivo hemostasis experiments. Polyacrylamide was shown to have favorable acoustic properties that varied linearly with acrylamide concentration from 10% to 20% weight in volume. Attenuation coefficient, sound speed and impedance ranged from 0.08 to 0.14 dB/cm at 1 MHz, 1546 to 1595 m/s and 1.58 to 1.68 Mrayl, respectively. An intraoperative in vivo hemostasis experiment in a sheep model demonstrated that the gel-coupled transducer was capable of inducing hemostasis in actively bleeding splenic and hepatic incisions. The results of this study show that polyacrylamide may be a promising coupling material for focused US therapy.

Acoustics↗

High-intensity focused US: a potential new treatment for GI bleeding.

BACKGROUND: High-intensity focused US has been shown to achieve hemostasis in lacerated large veins and arteries. High-intensity focused US was studied as a potential endoscopic treatment for GI bleeding. METHODS: A segment of the auricular vein of the rabbit was lacerated longitudinally and then treated with a high-intensity focused US transducer driven at 3.9 MHz (focal intensity of 750 W/cm(2)) in 15 animals until hemostasis was achieved. Sham treatment was delivered to 3 vessels. Rabbits were euthanized on days 0, 2, 7, 14, and 28 to allow for histologic evaluation of the response to treatment. RESULTS: Hemostasis was achieved in all treated vessels and in none of the sham treatments. Mean treatment time was 13 seconds. Histology initially demonstrated acute thermal injury with subsequent thrombus formation and chronic inflammation leading to replacement of the vessel by fibrous scar tissue. CONCLUSIONS: High-intensity focused US causes hemostasis in acutely bleeding veins and results in occlusion of treated vessel with subsequent granulation tissue formation.

Animals↗

Cavitation bubble cluster activity in the breakage of kidney stones by lithotripter shockwaves.

BACKGROUND AND PURPOSE: There is strong evidence that cavitation bubble activity contributes to stone breakage and that shockwave-bubble interactions are involved in the tissue trauma associated with shockwave lithotripsy. Cavitation control may thus be a way to improve lithotripsy. MATERIALS AND METHODS: High-speed photography was used to analyze cavitation bubble activity at the surface of artificial and natural kidney stones during exposure to lithotripter shockwaves in vitro. RESULTS: Numerous individual bubbles formed on the surfaces of stones, but these bubbles did not remain independent but rather combined to form clusters. Bubble clusters formed at the proximal and distal ends and at the sides of stones. Each cluster collapsed to a narrow point of impact. Collapse of the proximal cluster eroded the leading face of the stone, and the collapse of clusters at the sides of stones appeared to contribute to the growth of cracks. Collapse of the distal cluster caused minimal damage. CONCLUSION: Cavitation-mediated damage to stones is attributable, not to the action of solitary bubbles, but to the growth and collapse of bubble clusters.

Calcium Sulfate↗

Water-cooled, high-intensity ultrasound surgical applicators with frequency tracking.

High-intensity, focused ultrasound (HIFU) applicators have been developed for arresting bleeding with the ultimate intent of use in surgery. The design uses a tapered titanium component for transmission coupling of the ultrasound energy from a spherically curved transducer to biological tissues. The nominal operating frequency is 5.5 MHz, in a highly resonant mode (quality factor of 327 with water load). Liquid cooling is used to remove energy loss important at net applied power greater than 18 W/cm2 at the surface of the piezoelectric element. A downward resonance frequency shift (>20 kHz) occurs, even with cooling, as the applicator warms with normal operation. A feedback technique is used for maintaining the excitation near optimum resonance. Standing wave ratios of the applied power of 1.6 or less are thus sustained. The system and applicators have been found to be highly robust, effective in achieving hemostasis in the hemorrhaging liver, spleen, lung, or blood vessels in rabbit and pig experiments. One unit has been operated for over 1.7 hours in treating organ hemorrhage in blunt trauma experiments with nine swine with electrical net power of up to 158 W (31 W/cm2 across the transducer) and intensity of 2560 W/cm2 at focus.

Animals↗

A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents.

Contrast bubble destruction is important in several new diagnostic and therapeutic applications. The pressure threshold of destruction is determined by the shell material, while the propensity for of the bubbles to undergo inertial cavitation (IC) depends both on the gas and shell properties of the ultrasound contrast agent (UCA). The ultrasonic fragmentation thresholds of three specific UCAs (Optison, Sonazoid, and biSpheres), each with different shell and gas properties, were determined under various acoustic conditions. The acoustic emissions generated by the agents, or their derivatives, characteristic of IC after fragmentation, was also compared, using cumulated broadband-noise emissions (IC "dose"). Albumin-shelled Optison and surfactant-shelled Sonazoid had low fragmentation thresholds (mean = 0.13 and 0.15 MPa at 1.1 MHz, 0.48 and 0.58 MPa at 3.5 MHz, respectively), while polymer-shelled biSpheres had a significant higher threshold (mean = 0.19 and 0.23 MPa at 1.1 MHz, 0.73 and 0.96 MPa for thin- and thick-shell biSpheres at 3.5 MHz, respectively, p<0.01). At comparable initial concentrations, surfactant-shelled Sonazoid produced a much larger IC dose after shell destruction than did either biSpheres or Optison (p<0.01). Thick-shelled biSpheres had the highest fragmentation threshold and produced the lowest IC dose. More than two and five acoustic cycles, respectively, were necessary for the thin- and thick-shell biSpheres to reach a steady-state fragmentation threshold.

Air Pressure↗

Kidney damage and renal functional changes are minimized by waveform control that suppresses cavitation in shock wave lithotripsy.

PURPOSE: In studies to understand better the role of cavitation in kidney trauma associated with shock wave lithotripsy we assessed structural and functional markers of kidney injury when animals were exposed to modified shock waves (pressure release reflector shock pulses) that suppress cavitation. Experiments were also performed in isolated red blood cells, an in vitro test system that is a sensitive indicator of cavitation mediated shock wave damage. MATERIALS AND METHODS: We treated 6-week-old anesthetized pigs with shock wave lithotripsy using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia) fitted with its standard brass ellipsoidal reflector (rigid reflector) or with a pressure release reflector insert. The pressure release reflector transposes the compressive and tensile phases of the lithotriptor shock pulse without otherwise altering the positive pressure or negative pressure components of the shock wave. Thus, with the pressure release reflector the amplitude of the incident shock wave is not changed but cavitation in the acoustic field is stifled. The lower pole of the right kidney was treated with 2,000 shocks at 24 kV. Glomerular filtration rate, renal plasma flow and tubular extraction of para-aminohippurate were measured in the 2 kidneys 1 hour before and 1 and 4 hours after shock wave lithotripsy, followed by the removal of each kidney for morphological analysis. In vitro studies assessed shock wave induced lysis to red blood cells in response to rigid or pressure release reflector shock pulses. RESULTS: Sham shock wave lithotripsy had no significant effect on kidney morphology, renal hemodynamics or para-aminohippurate extraction. Shock waves administered with the standard rigid reflector induced a characteristic morphological lesion and functional changes that included bilateral reduction in renal plasma flow, and unilateral reduction in the glomerular filtration rate and para-aminohippurate extraction. When the pressure release reflector was used, the morphological lesion was limited to hemorrhage of vasa recta vessels near the tips of renal papillae and the only change in kidney function was a decrease in the glomerular filtration rate at the 1 and 4-hour periods in shock wave treated kidneys. Red blood cell lysis in vitro was significantly lower with the pressure release reflector than with the rigid reflector. CONCLUSIONS: These data demonstrate that shock wave lithotripsy damage to the kidney is reduced when cavitation is suppressed. This finding supports the idea that cavitation has a prominent role in shock wave lithotripsy trauma.

Animals↗

High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo.

High-intensity focused ultrasound (HIFU) has been shown to generate lesions that destroy brain tissue while disrupting the blood-brain barrier (BBB) in the periphery of the lesion. BBB opening, however, has not been shown without damage, and the mechanisms by which HIFU induces BBB disruption remain unknown. We show that HIFU is capable of reversible, nondestructive, BBB disruption in a targeted region-of-interest (ROI) (29 of 55 applications; 26 of 55 applications showed no effect); this opening reverses after 72 h. Light microscopy demonstrates that HIFU either entirely preserves brain architecture while opening the BBB (18 of 29 applications), or generates tissue damage in a small volume within the region of BBB opening (11 of 29 applications). Electron microscopy supports these observations and suggests that HIFU disrupts the BBB by opening capillary endothelial cell tight junctions, an isolated ultrastructural effect that is different from the mechanisms through which other (untargeted) modalities, such as hyperosmotic solutions, hyperthermia and percussive injury disrupt the BBB.

Animals↗

The disappearance of ultrasound contrast bubbles: observations of bubble dissolution and cavitation nucleation.

The destruction process of biSphere and Optison ultrasound (US) contrast microbubbles were studied at 1.1 MHz. High-amplitude tone bursts caused shell disruption and/or fragmentation of the microbubbles, leading to dissolution of the freed gas. The bubble destruction and subsequent dissolution process was imaged with a high pulse-repetition frequency (PRF) 10-cycle, 5-MHz bistatic transducer configuration. Three types of dissolution profiles were measured: In one case, biSphere microbubbles showed evidence of dissolution through resonance, during which a temporary increase in the scattering amplitude was observed. In another case, both biSphere and Optison microbubbles showed evidence of fragmentation, during which the scattering amplitude decreased rapidly. Finally, in some cases, we observed the impulsive growth and subsequent rapid decay of signals that appear to be due to cavitation nucleation. Simulations of bubble dissolution curves show good agreement with experiments.

Albumins↗

In vitro sonoluminescence and sonochemistry studies with an electrohydraulic shock-wave lithotripter.

Sonoluminescence and sonochemistry from a cavitation field generated by an electrohydraulic shock-wave lithotripter were investigated as functions of spark discharge voltage (13 to 21 kV) and pulse-repetition frequency (PRF) (0.5 to 2.0 Hz). Sonochemical activity, measured with an iodide dosimeter, increased with both voltage and PRF. Sonoluminescence was measured in an acoustically matched light-tight box. The envelope of the light intensity was measured in a temporally gated region extending from the initial arrival of the shock wave (resulting in bubble compression) to the final inertial collapse of the bubble cloud, which follows hundreds of micros after passage of the shock wave. The initial compression resulted in greater sonoluminescence emissions, suggesting that the initial bubble compression due to the leading positive pressure spike from the lithotripter generated higher temperatures than the inertial collapse of the bubble. These unexpected results are consistent with some recent calculations in which the vapor pressure of the liquid limits compressional heating.

Acoustics↗

Prefocal alignment improves stone comminution in shockwave lithotripsy.

BACKGROUND: The Dornier HM-3 machine continues to be one of the most effective lithotripters in use. However, tissue damage occurs in most, if not all, shockwave lithotripsy (SWL) treatments. Cavitation appears to contribute to desired stone comminution as well as to undesired tissue damage. Studies of cavitation in electrohydraulic shockwave lithotripters indicate that the greatest cavitation activity occurs, not at the geometric focus, F2, but at a site proximal to F2 by 1 to 3 cm. In clinical practice, however, stones are aligned with F2. MATERIALS AND METHODS: In vitro stone comminution, hemolysis, and free-radical production were assessed along the focal axis, and pig kidneys treated with SWL in vivo were sectioned to determine the extent of hemorrhagic injury along the focal axis. Model gypsum stones received 200 shockwaves in vitro at 18 kV. RESULTS: At F2, the average number of fragments >1.5 mm was 1.3 +/- 0.5, and the weight loss was 11.3 +/- 1.1%. At 2 cm from F2 (F2-2 cm), these values increased to 4 +/- 2.8 and 16.1 +/- 4.2%, respectively. Samples of 10% hematocrit blood were similarly exposed. Hemolysis was equivalent at F2-2 cm (14.7 +/- 2.3%) and F2 (15.2 +/- 3%) but decreased significantly at all other positions. Samples of iodine solution received 1500 shockwaves at 20 kV. Hydroxyl radical production was greatest at F2-2 cm (0.384 +/- 0.035 microM) and decreased significantly distal to this position. The volume of tissue injury in pig kidneys was greatest with prefocal shockwave exposure. CONCLUSION: Stone comminution may be achieved more rapidly without greater tissue damage by a simple shift in stone alignment to F2-2 cm.

Animals↗

Spleen hemostasis using high-intensity ultrasound: survival and healing.

BACKGROUND: Previous studies have shown that high-intensity focused ultrasound (HIFU) can effectively control bleeding of incised livers and spleens and punctured vessels. This current study investigated the long-term safety of HIFU in splenic hemostasis. METHODS: A total of 21 rabbits were randomly assigned to two groups: HIFU treatment (n = 14), and sham treatment (n = 7). All animals underwent sterile laparotomy and splenic exposure. The HIFU-treated animals received splenic incisions, 8 to 10 mm long and 4 to 5 mm deep, and immediate 9.6-MHz HIFU until hemostasis was achieved. After recovery, ultrasound images, blood samples, and histologic samples were collected on days 0, 1, 3, 7, 14, 28, and 60. RESULTS: All 14 splenic injuries were hemostatic after an average of 96 seconds of HIFU application. There was evidence of rebleeding in one animal between days 3 and 7 posttreatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between HIFU and sham groups. Histologic examination up to 60 days posttreatment revealed scarring and spleen tissue regeneration at the treatment site. CONCLUSION: HIFU provides an effective and safe method of achieving hemostasis after acute splenic injury.

Animals↗

Quantitative investigation of acoustic streaming in blood.

Acoustic streaming may have practical utility in diagnostic medical ultrasound in distinguishing between stagnant blood and tissue as well as clotted and unclotted blood. This distinction can be difficult with conventional ultrasound but have high value in managing trauma patients with internal hemorrhage. Ultrasound energy applies a force to blood by momentum transfer, resulting in bulk streaming that is a function of the acoustic attenuation, sound speed, acoustic intensity, blood viscosity, and the boundary conditions posed by the geometry around the hematoma. A simple tubular model was studied analytically, by finite element simulation, and experimentally by in vitro measurement. The simulation agreed closely with measurements while the analytic solutions were found to be valid only for beam diameters approximating the diameter of the tubular channel. Experimentally, the acoustic streaming in blood decreased as the blood began to clot and the streaming flow was not detected in clotted blood. In contrast, the echogenicity of the same blood samples did not change appreciably from the unclotted to the clotted state for the stagnant blood studied. Streaming detection appears to offer a potential tool for improving hemorrhage diagnosis.

Acoustics↗

A novel cavitation probe design and some preliminary measurements of its application to megasonic cleaning.

Cavitation is an effective physical mechanism for concentrating mechanical energy. Accordingly, it has wide applications in such diverse fields as sonochemistry, in which chemical reactions are initiated or accelerated, or in the electronic component cleaning industry in which particles (and other materials) are removed from surfaces. However, devices designed to act as cavitation monitors have had little success, partly because their intrusiveness often affects the cavitation field itself. Presented here is a brief description of a unique cavitation monitor that utilizes the phenomenon of sonoluminescence as an indirect quantifier of cavitation. It appears to work efficiently over a broad range of acoustic field intensities and its application to megasonic cleaning has provided interesting and valuable insights into this technology.

Journal Article↗

Effect of overpressure and pulse repetition frequency on cavitation in shock wave lithotripsy.

Cavitation appears to contribute to tissue injury in lithotripsy. Reports have shown that increasing pulse repetition frequency [(PRF) 0.5-100 Hz] increases tissue damage and increasing static pressure (1-3 bar) reduces cell damage without decreasing stone comminution. Our hypothesis is that overpressure or slow PRF causes unstabilized bubbles produced by one shock pulse to dissolve before they nucleate cavitation by subsequent shock pulses. The effects of PRF and overpressure on bubble dynamics and lifetimes were studied experimentally with passive cavitation detection, high-speed photography, and B-mode ultrasound and theoretically. Overpressure significantly reduced calculated (100-2 s) and measured (55-0.5 s) bubble lifetimes. At 1.5 bar static pressure, a dense bubble cluster was measured with clinically high PRF (2-3 Hz) and a sparse cluster with clinically low PRF (0.5-1 Hz), indicating bubble lifetimes of 0.5-1 s, consistent with calculations. In contrast to cavitation in water, high-speed photography showed that overpressure did not suppress cavitation of bubbles stabilized on a cracked surface. These results suggest that a judicious use of overpressure and PRF in lithotripsy could reduce cavitation damage of tissue while maintaining cavitation comminution of stones.

Equipment Design↗