低能量治疗性超声促进药物溶栓的实验研究

通过应用低能量治疗性超声对全血细胞血栓和纤维蛋白血栓的体外实验研究，结果显示：低能量治疗性超声能够促进药物溶栓的效果，与单用药物溶栓比较，效果可提高３２．５９～３９．３１％，并用对形成３天的血栓也有效；超声促进药物溶栓的效果与超声强度和超声处理的时间成正比（ｒ＝０．７０，０．９１）；药物浓度增加与超声助溶全血细胞血栓成正比（ｒ＝０．９０）与纤维蛋白血栓并不成正比。     

Enhancement of fibrinolysis in vitro by ultrasound.

The effect of ultrasound on the rate of fibrinolysis has been investigated using an in vitro system. Plasma or blood clots containing a trace label of 125I fibrin were suspended in plasma containing plasminogen activator and intermittently exposed to continuous wave 1-MHz ultrasound at intensities up to 8 W/cm2. Plasma clot lysis at 1 h with 1 microgram/ml recombinant tissue plasminogen activator (rt-PA) was 12.8 +/- 1.2% without ultrasound and was significantly (P = 0.0001) increased by exposure to ultrasound with greater lysis at 1 W/cm2 (18.0 +/- 1.4%), 2 W/cm2 (19.3 +/- 0.7%), 4 W/cm2 (22.8 +/- 1.8%), and 8 W/cm2 (58.7 +/- 7.1%). Significant increases in lysis were also seen with urokinase at ultrasound intensities of 2 W/cm2 and above. Exposure of clots to ultrasound in the absence of plasminogen activator did not increase lysis. Ultrasound exposure resulted in a marked reduction in the rt-PA concentration required to achieve an equivalent degree of lysis to that seen without ultrasound. For example, 15% lysis occurred in 1 h at 1 microgram/ml rt-PA without ultrasound or with 0.2 microgram/ml with ultrasound, a five-fold reduction in concentration. Ultrasound at 1 W/cm2 and above also potentiated lysis of retracted whole blood clots mediated by rt-PA or urokinase. The maximum temperature increase of plasma clots exposed to 4 W/cm2 ultrasound was only 1.7 degrees C, which could not explain the enhancement of fibrinolysis. Ultrasound exposure did not cause mechanical fragmentation of the clot into sedimentable fragments, nor did it alter the sizes of plasmic derivatives as demonstrated by SDS polyacrylamide gel electrophoresis. We conclude that ultrasound at 1 MHz potentiates enzymatic fibrinolysis by a nonthermal mechanism at energies that can potentially be applied and tolerated in vivo to accelerate therapeutic fibrinolysis.     

Intracranial temperature elevation from diagnostic ultrasound

Tissues of the central nervous system are sensitive to damage by physical agents, such as heat and ultrasound. Exposure to pulsed spectral Doppler ultrasound can significantly heat biologic tissue because of the relatively high intensities used and the need to hold the beam stationary during examinations. This has significant implications for sensitive neural tissue such as that exposed during spectral Doppler flow studies of fetal cerebral vessels. Recent changes in the FDA regulation allow delivery of almost eight times higher intensity into the fetal brain by ultrasound devices that incorporate an approved real-time output display in their design. In this situation, ultrasound users are expected to assess the risk/benefit ratio based on their interpretation of equipment output displays (including the thermal index, TI) and an understanding of the significance of biologic effects. To assist in the assessment of potential thermally mediated bioeffects, a number of conclusions can be drawn from the published scientific literature: the amount of ultrasound-induced intracranial heating increases with gestational age and the development of fetal bone; pulsed spectral Doppler ultrasound can produce biologically significant heating in the fetal brain; the rate of heating near bone is rapid, with approximately 75% of the maximum heating occurring within 30 s; blood flow has minimal cooling effect on ultrasound-induced heating of the brain when insonated with narrow focused clinical beams; the threshold for irreversible damage in the developing embryo and fetal brain is exceeded when a temperature increase of 4 degrees C is maintained for 5 min; an ultrasound exposure that produces a temperature increase of up to 1.5 degrees C in 120 s does not elicit measurable electrophysiologic responses in fetal brain; for some exposure conditions, the thermal index (TI), as used in the FDA-approved output display standard, underestimates the extent of ultrasound-induced intracranial temperature increase.     

Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro.

OBJECTIVE: To evaluate whether ultrasound, applied over a distance of several centimeters and in the absence of thrombolytic agents, may have a thrombolytic effect on blood clots. METHODS: Low-frequency (20 kHz) continuous wave ultrasound at different intensity levels (0.15-1.2 W/cm2) and exposure times (5, 10, and 20 minutes) was assessed for its potential to induce thrombolysis of fresh human blood clots. The ultrasound effect was also studied in combination with recombinant tissue-type plasminogen activator-mediated thrombolysis. Experiments were carried out in a flow model in degassed sodium phosphate buffer at 37 degrees C at a distance of 3 cm from the ultrasonic probe to the blood clots. Regardless of ultrasound exposure times, blood clots in all experimental groups and the control group were left in the flow system for 20 minutes. RESULTS: The use of ultrasound alone showed a significant thrombolytic effect compared with the control group, with a statistically significant effect at 0.15 W/cm2 and exposure of 10 minutes (P = .02). There was a clear correlation between the extent of weight loss and the chosen intensity level and exposure time. Complete disruption in 8 of 10 blood clots occurred at 1.2 W/cm2 within 10 min. Addition of ultrasound to recombinant tissue-type plasminogen activator-mediated thrombolysis significantly enhanced thrombolysis compared with application of recombinant tissue-type plasminogen activator or ultrasound alone (P = .0001), with the results pointing toward a purely additive, nonsynergistic effect of the 2 treatment modalities. Lysis was more effective in fresh thrombi. CONCLUSIONS: The use of low-frequency ultrasound alone, without addition of a thrombolytic drug, has the potential to induce thrombolysis over a distance. Combination of ultrasound with recombinant tissue-type plasminogen activator is superior to either treatment alone. Ultrasound is a promising tool for developing an alternative or additional treatment modality for acute cerebral vessel occlusion.     

Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent

Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity((R)), was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity((R)) and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity((R)). A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p < 0.0001, n = 24). The largest mean penetration depth of rt-PA (222 mum) and plasminogen (241 mum) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment. (E-mail: Christy.Holland@uc.edu).     

Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz

Inertial cavitation is hypothesized to be a mechanism by which ultrasound (US) accelerates the dissolution of human blood clots when the clot is exposed to a thrombolytic agent such as tissue plasminogen activator (t-PA). To test this hypothesis, radiolabeled fibrin clots were exposed or sham-exposed in vitro to 1 MHz c.w. US in a rotating sample holder immersed in a water-filled tank at 37 degrees C. Percent clot dissolution after 60 min of US exposure was assessed by removing the samples, centrifuging, and measuring the radioactivity of the supernatant fluid relative to the pelletized material. To suppress acoustic cavitation, the exposure tank was contained within a hyperbaric chamber capable of pneumatic pressurization to 10 atmospheres (gauge). Various combinations of static pressure (0, 2, 5, and 7.5 atm gauge), US (0 or 4 W/cm(2) SATA), and t-PA (0 or 10 microg/mL) were employed, showing statistically significant reductions in thrombolytic activity as static pressure increased. To gain further insight, an active cavitation detection scheme was employed in which 1-micros duration tonebursts of 20-MHz US (< 1 kPa peak negative pressure, 1 Hz PRF) were used to interrogate clots subjected to US and static pressure. Results of this cavitation detection scheme showed that scattering from within the clot and broadband acoustic emissions that were both present during insonification were significantly reduced with application of static pressure. However, only about half of the acceleration of thrombolysis due to US could be removed by static pressure, suggesting the possibility of other mechanisms in addition to inertial cavitation.     

Characterization of ultrasound propagation through ex-vivo human temporal bone

Adjuvant therapies that lower the thrombolytic dose or increase its efficacy would represent a significant breakthrough in the treatment of patients with ischemic stroke. The objective of this study was to perform intracranial measurements of the acoustic pressure field generated by 0.12, 1.03 and 2.00-MHz ultrasound transducers to identify optimal ultrasound parameters that would maximize penetration and minimize aberration of the beam. To achieve this goal, in vitro experiments were conducted on five human skull specimens. In a water-filled tank, two unfocused transducers (0.12 and 1.03 MHz) and one focused transducer (2.00 MHz) were consecutively placed near the right temporal bone of each skull. A hydrophone, mounted on a micropositioning system, was moved to an estimated location of the middle cerebral artery (MCA) origin, and measurements of the surrounding acoustic pressure field were performed. For each measurement, the distance from the position of maximum acoustic pressure to the estimated origin of the MCA inside the skulls was quantified. The -3 dB depth-of-field and beamwidth in the skull were also investigated as a function of the three frequencies. Results show that the transducer alignment relative to the skull is a significant determinant of the detailed behavior of the acoustic field inside the skull. For optimal penetration, insonation normal to the temporal bone was needed. The shape of the 0.12-MHz intracranial beam was more distorted than those at 1.03 and 2.00 MHz because of the large aperture and beamwidth. However, lower ultrasound pressure reduction was observed at 0.12 MHz (22.5%). At 1.03 and 2.00 MHz, two skulls had an insufficient temporal bone window and attenuated the beam severely (up to 96.6% pressure reduction). For all frequencies, constructive and destructive interference patterns were seen near the contralateral skull wall at various elevations. The 0.12-MHz ultrasound beam depth-of-field was affected the most when passing through the temporal bone and showed a decrease in size of more than 55% on average. The speed of sound in the temporal bone of each skull was estimated at 1.03 MHz and demonstrated a large range (1752.1 to 3285.3 m/s). Attenuation coefficients at 1.03 and 2.00 MHz were also derived for each of the five skull specimens. This work provides needed information on ultrasound beam shapes inside the human skull, which is a necessary first step for the development of an optimal transcranial ultrasound-enhanced thrombolysis device.     

Systematic Analysis of Combined Thrombolysis Using Ultrasound and Different Fibrinolytic Drugs in an in Vitro Clot Model of Intracerebral Hemorrhage

Adequate removal of blood clots by minimally invasive surgery seems to correlate with a better clinical outcome in patients with intracerebral hemorrhages (ICHs). Moreover, neurotoxic effects of recombinant tissue plasminogen activator have been reported. The aim of this study was to improve fibrinolysis using an intra-clot ultrasound application with tenecteplase and urokinase in our established ICH clot model. One hundred thirty clots were produced from 25 or 50 mL of human blood, incubated for different periods and equipped with drainage, through which an ultrasound catheter was placed in 65 treatment clots for 1 h, randomly allocated into three groups: administration of ultrasound, administration of 60 IU of tenecteplase or administration of 30,000 IU urokinase. Relative end weights were compared. This study found a significant increase in thrombolysis caused by a combination of ultrasound and fibrinolytic drugs, whereas ultrasound and tenecteplase are significantly more effective in the treatment of larger and aged clots.     

Duty cycle dependence of ultrasound enhanced thrombolysis in a human clot model

Combined ultrasound and tissue plasminogen activator (rt-PA) therapy, or ultrasound enhanced thrombolysis (UET), has been shown to improve recanalization in patients with acute ischemic stroke. We measured the effect of ultrasound duty cycle on the lytic efficacy of 120 kHz UET in an in vitro human clot model. The hypothesis was that an increase in duty cycle increases rt-PA lytic efficacy. Human whole blood clots were exposed to 120-kHz ultrasound and rt-PA for 30 min in human plasma. The duty cycle ranged from 0% to 80%, where 0% represents sham exposure. Clot lytic rate was measured by recording the clot width over time. The clot width after 30 min exposure to rt-PA and ultrasound decreases with increasing duty cycle. The initial lytic rate increased linearly with duty cycle.     

Acceleration of thrombolysis with ultrasound through the cranium in a flow model

Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window. Neurological outcome depends on the recanalization time of the occluded vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic fibrinolysis in vitro. We examined the effects of transcranially applied US on recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exposure (0.5 W/cm(2); spatial peak, temporal peak intensity). Transcranial and direct US application in combination with rt-PA significantly (p<0.001) shortened recanalization time, increased perfusion flow and reperfusion rate in comparison with rt-PA-mediated thrombolysis alone. Recanalization rate within 30 min was 90-100% in the US-exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate reperfusion and recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated thrombolysis. Shortening of recanalization time could contribute to optimizing effects of acute thrombolytic stroke therapy.     

Ultrasound properties of human prostate tissue during heating

Changes in the ultrasound (US) properties of tissue during heating affect the delivery of US thermal therapy and may provide a basis for US image monitoring of thermal therapy. The US attenuation coefficient and backscatter power of fresh human prostate tissue were measured as the tissue was heated. Samples of human prostate were obtained directly from autopsies and heated rapidly to final temperatures of 45 degrees C, 50 degrees C, 55 degrees C, 60 degrees C and 65 degrees C. A 5.0-MHz transducer was scanned in a raster pattern over the tissue and radiofrequency (RF) data were collected at 36 uncorrelated positions. Both attenuation and backscatter were measured over the frequency range 3.5 to 7.0 MHz at each min of a 30-min heating. Little change was observed in attenuation or backscatter at 55 degrees C or less. The attenuation coefficient and backscatter power increased by factors of 1.25 and 5, respectively, during the 60 degrees C heating. During the 65 degrees C heating, the same properties showed increases by factors of 2.7 and 9.     

Enhanced Clot Dissolution In Vitro by 1.8-MHz Pulsed Ultrasound

Clinical studies of acute stroke patients have shown that the use of high frequency, low energy transcranial “diagnostic” ultrasound (US) enhances thrombolysis (sonothrombolysis). In contrast, a previous in vitro study using a clot preparation with coagulation induced by recalcification failed to reproduce an effect of “diagnostic” transcranial US on thrombolysis. We sought to evaluate this contradiction in an in vitro model with modified clot preparation. The efficacy of 1.8-MHz pulsed-wave (PW) ultrasound (US) emitted by a commercial probe on thrombolysis was tested. Whole blood clots from 0.5-mL venous blood samples were insonated for 1 h through a human temporal bone, using 1.8-MHz PW US emitted by a diagnostic device. The experiment was performed with or without recombinant tissue-type plasminogen activator (rt-PA) at a concentration of 10 μg/mL. Thrombolysis was measured by means of clot weight loss after 1 h of insonation. A reduction in thrombus weight occurred when US was used in combination with rt-PA, compared with rt-PA alone (78.7% ± 2.1% versus 70.8% ± 4.1%, p ≤ 0.0001). Repetition of the experiment produced identical results (76.9% ± 2.5%, compared with control, p = 0.001). Even without rt-PA, US was effective (41.0% ± 1.7% versus 36.7% ± 3.7%, p = 0.04). The results of this in vitro study support the clinical observation that diagnostic transcranial US, with or without rt-PA, enhances thrombolysis. (E-mail: juergeneggers@gmx.net)     

A comparison of AIUM/NEMA thermal indices with calculated temperature rises for a simple third-trimester pregnancy tissue model. American Institute of Ultrasound in Medicine/National Electrical Manufacturers Association.

Temperature rises due to diagnostic ultrasound exposures have been calculated for a simple third-trimester pregnancy tissue model. This consisted of a layer of soft tissue representing the abdominal/uterine wall, a layer of liquid and a layer of fetal bone. The ultrasound field parameter used in the calculations was the temporal average of the square of the acoustic pressure (p2TA), measured in water but corrected for attenuation in the tissue model. The three-dimensional (3-D) distribution of p2TA was measured for five probes operating in B-mode, and four probes operating in pulsed Doppler and color flow imaging modes. The calculated temperature rises were compared to the AIUM/NEMA-defined thermal indices appropriate to third-trimester scanning. In B-mode, the ratio of calculated temperature rise to thermal index varied between 0.62 and 1.25, with calculated temperature rises as high as 1.4 degrees C. In color-flow imaging mode, this ratio varied between 1.26 and 2.45 and, in pulsed Doppler mode, between 1.46 and 2.92, with calculated temperature rises as high as 1.8 degrees C and 5.8 degrees C, respectively. These results indicate that, for scanning situations where bone is insonated through an overlying low attenuation liquid layer, the thermal index may substantially underestimate the maximum temperature rise that could occur.     

Enhancement of enzymatic fibrinolysis with 2-MHz ultrasound and microbubbles.

BACKGROUND: Microbubbles used for echo-contrast agents accelerate enzymatic fibrinolysis of clots exposed to low-frequency ultrasound (US). It is not known whether microbubbles are also effective in enhancing high-frequency US-driven enzymatic fibrinolysis. METHODS AND RESULTS: Calibrated whole blood clots were exposed to US, or US and galactose-based microbubbles (Levovist), with or without recombinant tissue plasminogen activator (rt-PA) in an in-vitro flow system. We used low-intensity, 2-MHz, pulsed wave US. Relative weight reduction of clot +/- SD was 30.7 +/- 9.5% after exposure to microbubbles, rt-PA and US, 13.1 +/- 2.6% after exposure to rt-PA and US, 10.9 +/- 3.6% after exposure to microbubbles and US, and 6.1 +/- 1.9% after exposure to US alone. anova demonstrated a significant effect of rt-PA (P =0.001), microbubbles (P = 0.012), and interaction of both (P = 0.022). CONCLUSIONS: The application of galactose-based microbubbles (Levovist) strongly accelerates lysis of clots exposed to 2 MHz, low-intensity US in vitro both with and without rt-PA. The findings suggest a synergy between microbubbles and rt-PA. These methods routinely used for transcranial diagnostic applications have the potential to improve the efficacy of intravenous rt-PA in acute ischemic stroke.     

Noninvasive Thrombolysis Using Pulsed Ultrasound Cavitation Therapy – Histotripsy

Clinically available thrombolysis techniques are limited by either slow reperfusion (drugs) or invasiveness (catheters) and carry significant risks of bleeding. In this study, the feasibility of using histotripsy as an efficient and noninvasive thrombolysis technique was investigated. Histotripsy fractionates soft tissue through controlled cavitation using focused, short, high-intensity ultrasound pulses. In vitro blood clots formed from fresh canine blood were treated by histotripsy. The treatment was applied using a focused 1-MHz transducer, with five-cycle pulses at a pulse repetition rate of 1 kHz. Acoustic pressures varying from 2 to 12 MPa peak negative pressure were tested. Our results show that histotripsy can perform effective thrombolysis with ultrasound energy alone. Histotripsy thrombolysis only occurred at peak negative pressure ≥6 MPa when initiation of a cavitating bubble cloud was detected using acoustic backscatter monitoring. Blood clots weighing 330 mg were completely broken down by histotripsy in 1.5 to 5 min. The clot was fractionated to debris with >96% weight smaller than 5 μm diameter. Histotripsy thrombolysis treatment remained effective under a fast, pulsating flow (a circulatory model) as well as in static saline. Additionally, we observed that fluid flow generated by a cavitation cloud can attract, trap and further break down clot fragments. This phenomenon may provide a noninvasive method to filter and eliminate hazardous emboli during thrombolysis. (E-mail: adamdm@umich.edu)     

Acoustic techniques for assessing the Optison destruction threshold.

OBJECTIVE: The purpose of this study was to identify the pressure threshold for the destruction of Optison (octafluoropropane contrast agent; Amersham Health, Princeton, NJ) using a laboratory-assembled 3.5-MHz pulsed ultrasound system and a clinical diagnostic ultrasound scanner. METHODS: A 3.5-MHz focused transducer and a linear array with a center frequency of 6.9 MHz were positioned confocally and at 90 degrees to each other in a tank of deionized water. Suspensions of Optison (5-8x10(4) microbubbles/mL) were insonated with 2-cycle pulses from the 3.5-MHz transducer (peak rarefactional pressure, or Pr, from 0.0, or inactive, to 0.6 MPa) while being interrogated with fundamental B-mode imaging pulses (mechanical index, or MI,=0.04). Scattering received by the 3.5-MHz transducer or the linear array was quantified as mean backscattered intensity or mean digital intensity, respectively, and fit with exponential decay functions (Ae-kt+N, where A+N was the amplitude at time 0; N, background echogenicity; and k, decay constant). By analyzing the decay constants statistically, a pressure threshold for Optison destruction due to acoustically driven diffusion was identified. RESULTS: The decay constants determined from quantified 3.5-MHz radio frequency data and B-mode images were in good agreement. The peak rarefactional pressure threshold for Optison destruction due to acoustically driven diffusion at 3.5 MHz was 0.15 MPa (MI=0.08). Furthermore, the rate of Optison destruction increased with increasing 3.5-MHz exposure pressure output. CONCLUSIONS: Optison destruction was quantified with a laboratory-assembled 3.5-MHz ultrasound system and a clinical diagnostic ultrasound scanner. The pressure threshold for acoustically driven diffusion was identified, and 3 distinct mechanisms of ultrasound contrast agent destruction were observed with acoustic techniques.     

Ultrasound measurement of the effect of temperature on microperfusion in the eye

Recent developments in ultrasound (US) technology have allowed the study of microperfusion in the anterior segment of the eye. Our aim was to determine the effect of the thermal environment on blood flow in the anterior segment. We measured blood flow in the major arterial circle of five rabbits. A 38-MHz US transducer was coupled to the eye with a normal saline water-bath with temperature controlled from 1 degrees C to 38 degrees C. The major arterial circle was localized and imaged using the swept-scan technique and M-mode data were then acquired for measurement of pulsatile flow. Peak systolic and mean velocity averaged 4.51 and 1.32 mm/s, respectively. Positive correlations were found between peak systolic (1.69%/ degrees C) and mean (1.76%/ degrees C) velocities and temperature. Vessel diameter (mean = 178 microm) did not show any significant change with temperature. High-resolution US flowmetry demonstrated decreasing flow rates in the iris with decreasing temperature.     

Correlation of cavitation with ultrasound enhancement of thrombolysis

Pulsed ultrasound, when used as an adjuvant to recombinant tissue plasminogen activator (rt-PA), has been shown to enhance thrombolysis in the laboratory as well as in clinical trials for the treatment of ischemic stroke. The exact mechanism of this enhancement has not yet been elucidated. In this work, stable and inertial cavitation (SC and IC) are investigated as possible mechanisms for this enhancement. A passive cavitation detection scheme was utilized to measure cavitation thresholds at 120 kHz (80% duty cycle, 1667 Hz pulse repetition frequency) for four host fluid and sample combinations: plasma, plasma with rt-PA, plasma with clot and plasma with clot and rt-PA. Following cavitation threshold determination, clots were exposed to pulsed ultrasound for 30 min in vitro using three separate ultrasound treatment regimes: (1) no cavitation (0.15 MPa), (2) SC alone (0.24 MPa) or (3) SC + IC combined (0.36 MPa) in the presence of rt-PA. Percent clot mass loss after each treatment was used to determine thrombolysis efficacy. The highest percent mass loss was observed in the stable cavitation regime (26%), followed by the combined stable and inertial cavitation regime (20.7%). Interestingly, the percent mass loss in clots exposed to ultrasound without cavitation (13.7%) was not statistically significantly different from rt-PA alone (13%) [p > 0.05]. Significant enhancement of thrombolysis correlates with presence of cavitation and stable cavitation appears to play a more important role in the enhancement of thrombolysis. (E-mail: ).     

脉冲高强度聚焦超声在治疗中的应用

脉冲高强度聚集超声不像传统的高强度聚焦超声发射连续波消融组织,而是脉冲超声辐照局部组织机械能量的不连续积累。脉冲高强度聚焦超声辐照局部组织可以促进基因的转染和表达、靶向传输药物治疗肿瘤以及增强超声微泡造影剂的溶栓作用。本文综述了其在肿瘤、溶栓等方面的应用研究进展。     

Heating caused by selected pulsed Doppler and physiotherapy ultrasound beams measured using thermal test objects

OBJECTIVE: To assess the heating caused by selected pulsed Doppler and physiotherapy ultrasound beams by measurements made using thermal test objects. METHOD: Thermal test objects were used to measure temperature rises in selected ultrasound fields. These were compared with theoretical predictions based on standard exposure measurements. A separate thermocouple was used to measure heating at the transducer surface. RESULTS: Temperature rises of up to 6 degrees C were measured for Doppler fields using a thermal test object. The attenuation-corrected temperature rises that were measured generally agreed with calculated Thermal Indices. Temperature rises of up to 2 degrees C were observed for physiotherapy ultrasound fields in pulsed operation. CONCLUSION: Significant overlap between the measured temperature rises of selected pulsed Doppler and physiotherapy ultrasound fields was observed.