Continuous Wave Ultrasound Research Articles

Continuous Wave Ultrasound Testing Techniques

Currently, the primary method employed for ultrasound inspection is based on sending and detecting ultrasound pulses. Typically, pulse-based methods are essentially time-domain back-reflection methods, and the time-of-flight is the main measured parameter. Recently, continuous-wave methods have been developed in the radar and the fiber-optics fields, which demonstrate significantly better spatial resolution, higher signal-to-noise ratio, and ability to detect reflecting objects at very short distances. It is proposed to use the same approach to develop continuous-wave ultrasound inspection systems. The two main differences between the proposed continuous-wave ultrasonic testing and the classical pulsed ultrasound inspection method are: (i) in the continuous-wave ultrasonic testing method, the transmitted and received signals overlap in the time domain, while in the pulsed ultrasound inspection method the transmitted and received signals are separated in the time; and (ii) in the pulsed ultrasound inspection method the most important parameter is the time delay between the transmitted and received signals, while in the continuous-wave ultrasonic testing method the most informative parameters are the frequency and phase changes in the received signal in respect to modulated transmitted signal. This allows for additional flexibility in the continuous-wave ultrasonic measurements, through control of the frequency modulation. Also, the continuous-wave ultrasonic method potentially offers improved detection range and resolution; improved signal-to-noise ratio due to better energy efficiency and easier filtering; and reduced requirements on the voltage applied to the transducer, which in turn allows the use of simplified low-cost electronics. The theoretical basis of several continuous-wave ultrasound inspection technique is explained, and their advantages and limitations are discussed. Implementation of several prototype continuous-wave ultrasound testing systems is presented. Examples of the use of the systems for non-destructive testing are described.

A Randomized Trial of Therapeutic Ultrasound on Pain, Tenderness, and Muscle Stiffness Using a High and Low Intensity Model of Delayed Onset Muscle Soreness

Purpose: This study evaluated ultrasound (US) effectiveness in an experimental model of soft tissue injury, and examined the model, delayed onset muscle soreness (DOMS), as a variable in the outcome. Methods: One hundred and twenty females completed 30 repetitions (low-DOMS) or 70 repetitions (high-DOMS) of eccentric contractions of biceps brachii muscles and received one of four protocols: no US (control), placebo US, or 3 MHz US, pulsed 20% duty cycle, at either 0.6 W/cm2, spatial-average temporal-peak intensity (SATP) (0.12 W/cm2, spatial-average temporal-average intensity (SATA)) or 1.0 W/cm2, SATP (0.2 W/cm2 SATA). A further 60 females completed a low-DOMS protocol and received one of three protocols: placebo US, or continuous wave 3 MHz US at either 0.2 or 0.4 W/cm2, SATP/SATA. US was applied to biceps muscles for 5 minutes on days 1 to 3. Muscle soreness, tenderness, and stiffness were measured pre-DOMS induction and at 24, 48, and 72 hours post-induction. Results: Pulsed US, 20% duty cycle, at 0.6 W/cm2, SATP, (0.12 W/cm2, SATA) reduced muscle soreness in a low-DOMS but not in a high-DOMS protocol. Continuous wave US at 0.4 W/cm2, SATP/SATA reduced tenderness. Continuous US at 0.2 W/cm2, SATP/SATA was marginally effective on stiffness and tenderness. Conclusion: The results have implications for US management of acute soft tissue injury and the use of DOMS as an experimental model for soft tissue inflammation.

Feasibility of ultrasound tomography-guided localized mild hyperthermia using a ring transducer: Ex vivo and in silico studies.

As of 2022, breast cancer continues to be the most diagnosed cancer worldwide. This problem persists within the United States as well, as the American Cancer Society has reported that ∼12.5% of women will be diagnosed with invasive breast cancer over the course of their lifetime. Therefore, a clinical need continues to exist to address this disease from a treatment and therapeutic perspective. Current treatments for breast cancer and cancers more broadly include surgery, radiation, and chemotherapy. Adjuncts to these methods have been developed to improve the clinical outcomes for patients. One such adjunctive treatment is mild hyperthermia therapy (MHTh), which has been shown to be successful in the treatment of cancers by increasing effectiveness and reduced dosage requirements for radiation and chemotherapies. MHTh-assisted treatments can be performed with invasive thermal devices, noninvasive microwave induction, heating and recirculation of extracted patient blood, or whole-body hyperthermia with hot blankets. One common method for inducing MHTh is by using microwave for heat induction and magnetic resonance imaging for temperature monitoring. However, this leads to a complex, expensive, and inaccessible therapy platform. Therefore, in this work we aim to show the feasibility of a novel all-acoustic MHTh system that uses focused ultrasound (US) to induce heating while also using US tomography (UST) to provide temperature estimates. Changes in sound speed (SS) have been shown to be strongly correlated with temperature changes and can therefore be used to indirectly monitor heating throughout the therapy. Additionally, these SS estimates allow for heterogeneous SS-corrected phase delays when heating complex and heterogeneous tissue structures. Feasibility to induce localized heat in tissue was investigated in silico with a simulated breast model, including an embedded tumor using continuous wave US. Here, both heterogenous acoustic and thermal properties were modeled in addition to blood perfusion. We further demonstrate, with ex vivo tissue phantoms, the feasibility of using ring-based UST to monitor temperature by tracking changes in SS. Two phantoms (lamb tissue and human abdominal fat) with latex tubes containing varied temperature flowing water were imaged. The measured SS of the water at each temperature were compared against values that are reported in literature. Results from ex vivo tissue studies indicate successful tracking of temperature under various phantom configurations and ranges of water temperature. The results of in silico studies show that the proposed system can heat an acoustically and thermally heterogenous breast model to the clinically relevant temperature of 42°C while accounting for a reasonable time needed to image the current cross section (200ms). Further, we have performed an initial in silico study demonstrating the feasibility of adjusting the transmit waveform frequency to modify the effective heating height at the focused region. Lastly, we have shown in a simpler 2D breast model that MHTh level temperatures can be maintained by adjusting the transmit pressure intensity of the US ring. This work has demonstrated the feasibility of using a 256-element ring array transducer for temperature monitoring; however, future work will investigate minimizing the difference between measured SS and the values shown in literature. A hypothesis attributes this bias to potential volumetric average artifacts from the ray-based SS inversion algorithm that was used, and that moving to a waveform-based SS inversion algorithm will greatly improve the SS estimates. Additionally, we have shown that an all-acoustic MHTh system is feasible via in silico studies. These studies have indicated that the proposed system can heat a tumor within a heterogenous breast model to 42°C within a narrow time frame. This holds great promise for increasing the accessibility and reducing the complexity of a future all-acoustic MHTh system.

Inhibition of Human Breast Cancer Cell Proliferation by Low-Intensity Ultrasound Stimulation.

Cancer is characterized by uncontrolled cell proliferation, which makes novel therapies highly desired. In this study, the effects of near-field low-intensity pulsed ultrasound (LIPUS) stimulation on T47D human breast cancer cell and healthy immortalized MCF-12A breast epithelial cell proliferation were investigated in monolayer cultures. A customized ultrasound (US) exposure setup was used for the variation of key US parameters: intensity, excitation duration, and duty cycle. Cell proliferation was quantified by 5-bromo-2'-deoxyuridine and alamarBlue assays after LIPUS excitation. At a 20% duty cycle and 10-minute excitation period, we varied LIPUS intensity from to 100 mW/cm2 (spatial-average temporal-average) to find a gradual decrease in T47D cell proliferation, the decrease being strongest at 100 mW/cm2 . In contrast, healthy MCF-12A breast cells showed an increase in proliferation when exposed to the same conditions. Above a 60% duty cycle, T47D cell proliferation decreased drastically. Effects of continuous wave US stimulation were further explored by varying the intensity and excitation period. These experiments concluded that, irrespective of the waveform (pulsed or continuous), LIPUS stimulation could inhibit the proliferation of T47D breast cancer cells, whereas the same behavior was not observed in healthy cells. The study demonstrates the beneficial bioeffects of LIPUS on breast cancer cells and offers the possibility of developing novel US-mediated cancer therapy.

The effect of 220 kHz insonation scheme on rt-PA thrombolytic efficacy in vitro

Ultrasound-enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis is under development as an adjuvant to ischemic stroke therapy. The goal of this study was to design a pulsed ultrasound (US) exposure scheme that reduced intracranial constructive interference and tissue heating, and maintained thrombolytic efficacy relative to continuous wave (CW) insonation. Three 220 kHz US schemes were evaluated, two pulsed insonation schemes (15 cycles, 68 µs pulse duration, 33% or 62.5% duty cycle) and an intermittent CW insonation scheme (50 s active, 30 s quiescent) over a 30-min treatment period. An in silico study using a finite-difference model of transcranial US propagation was performed to estimate the intracranial acoustic field and temperature rise in the skull for each insonation scheme. In vitro measurements with flow were performed to assess thrombolysis using time-lapse microscopy. Intracranial constructive interference was not reduced with pulsed US using a pulse length of 15 cycles compared to intermittent CW US. The 33.3% duty cycle pulsed US scheme reduced heating in the temporal bone as much as 60% relative to the intermittent CW scheme. All insonation schemes promoted sustained stable cavitation in vitro and augmented thrombolysis compared to rt-PA alone (p < 0.05). Ultraharmonic (UH) and harmonic cumulative energy over a 30 min treatment period was significantly higher (p < 0.05) for the intermittent CW US scheme compared to either pulsed US scheme. Despite the difference in cavitation emissions, no difference was observed in the clot lysis between the three US schemes. These findings demonstrate that a 33.3% duty cycle pulsed US scheme with a 15-cycle burst can reduce bone heating and achieve equivalent thrombolytic efficacy as an intermittent CW scheme.

Activation of Piezo1 but Not NaV1.2 Channels by Ultrasound at 43 MHz

Ultrasound (US) can modulate the electrical activity of the excitable tissues, but the mechanisms underlying this effect are not understood at the molecular level or in terms of the physical modality through which US exerts its effects. Here, we report an experimental system that allows for stable patch-clamp recording in the presence of US at 43 MHz, a frequency known to stimulate neural activity. We describe the effects of US on two ion channels proposed to be involved in the response of excitable cells to US: the mechanosensitive Piezo1 channel and the voltage-gated sodium channel NaV1.2. Our patch-clamp recordings, together with finite-element simulations of acoustic field parameters indicate that Piezo1 channels are activated by continuous wave US at 43 MHz and 50 or 90 W/cm2 through cell membrane stress caused by acoustic streaming. NaV1.2 channels were not affected through this mechanism at these intensities, but their kinetics could be accelerated by US-induced heating.

Effects of low-intensity ultrasound on gramicidin D-induced erythrocyte edema.

To determine whether low-intensity ultrasound (US) can reduce red blood cell (RBC) edema and, if so, whether the US activity is associated with aquaporin 1 (AQP-1), a water channel in the cell membrane. Red blood cell edema was induced by gramicidin D treatment at 40 ng/mL for 20 minutes and evaluated by a hematocrit assay. Low-intensity continuous wave US at 1 MHz was applied to RBCs for the last 10 minutes of gramicidin D treatment. To determine whether US activity was associated with AQP-1, RBCs were treated with 40 μM mercuric chloride (HgCl(2)), an AQP-1 inhibitor, for 20 minutes at the time of gramicidin D treatment. Posttreatment morphologic changes in RBCs were observed by actin staining with phalloidin. Red blood cell edema increased significantly with gramicidin D at 20 (1.8%), 40 (6.7%), 60 (16.7%), and 80 (11.3%) ng/mL, reaching a peak at 60 ng/mL, compared to the control group (20 ng/mL, P = .019; 40, 60, and 80 ng/mL, P < .001). No significant RBC hemolysis was observed in any group. Edema induced by gramicidin D at 40 ng/mL was significantly reduced by US at 30 (3.4%; P = .003), 70 (4.4%; P = .001), and 100 (2.9%; P = .001) mW/cm(2). Subsequent experiments showed that edema reduction by US ranged from 7% to 10%. Cotreatment with HgCl(2) partially reversed the US effect and showed a significantly different level of edema compared to gramicidin D-alone and US-cotreated groups (P = .001). These results were confirmed by microscopic observation of RBC morphologic changes. Low-intensity US could reduce gramicidin D-induced RBC edema, and its effect appeared to at least partly involve regulation of AQP-1 activity. These results suggest that low-intensity US can be used as an alternative treatment to control edema and related disorders.

Membrane Damage Effect of Continuous Wave Ultrasound on K562 Human Leukemia Cells

This study investigated the bioeffects of ultrasound with a frequency of 1.1 MHz on human chronic myelogenous leukemia cell line K562. Membrane potential changes were evaluated by flow cytometry using fluorescent probe bis-(1,3-dibarbituric acid)-trimethine oxanol staining. Other related changes such as potassium ion efflux and intracellular calcium ion overload were also measured. The plasma membrane integrity was monitored by flow cytometry combined with fluorescein diacetate and propidium iodide double fluorescent dye staining. A cell-counting assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis were used to examine the viability of K562 cells after ultrasound exposure. The acoustic cavitation activity in ultrasound fields was assessed by monitoring hydroxyl radical production. As the ultrasonic intensity increased, the hydroxyl radical produced in the medium increased, and cell membrane damage and cell viability loss were enhanced. The ultrasonic intensity at 0.64 W/cm(2) did not cause substantial cell damage, whereas ultrasound exposure at 1 and 2.1 W/cm(2) could induce serious cell death (14.0% and 40.7%, respectively). Moreover, ultrasound at 0.64 W/cm(2) did not cause substantial membrane potential changes, whereas ultrasound exposure at 1 W/cm(2) could induce depolarization, and fast hyperpolarization occurred when the ultrasonic intensity increased to 2.1 W/cm(2). In addition, compared with control cells, in different ultrasound-treated cells, the potassium ion continuously outflowed with a prolonged incubation time, whereas the intracellular calcium ion oscillations became more apparent. The damaging effects of ultrasound on the cell membrane and cell viability were intensity dependent. The membrane potential changes may be due to acoustic cavitation accompanied by alterations in the balance of ions on opposite sides of the cellular membrane.

Cell Damage of Hepatoma-22 Cells Exposed to Continuous Wave Ultrasound

The cellular response of hepatoma-22 cells to ultrasonic irradiation and the potential cause for the action were evaluated. Hepatoma-22 cells were subjected to ultrasound irradiation at a frequency of 2.17 MHz and a spatial average intensity of 1.6 W/cm2 for variable periods of time, and several biological parameters were analyzed. The terephthalic acid (TA) dosimetry method was used to evaluate the efficacies of irradiation parameters on the acoustic cavitation activity by monitoring hydroxyl radical (OH) production. Lactate dehydrogenase (LDH) leakage was assayed to investigate cell membrane integrity. The polarization value of fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was measured to monitor plasma membrane fluidity. The malonaldehyde content in cells was determined to reflect lipid peroxidation. Trypan blue exclusion was used to detect cell viability. Additionally, electron microscopy was used to observe morphological changes. The generation of intracellular reactive oxygen species, mitochondria swelling and the loss of mitochondria membrane potential were also investigated. The results showed that 1) the concentration of ·OH production by ultrasonic irradiation in air-saturated cell suspensions increased as ultrasound exposure time increased; 2) compared with control, lactate dehydrogenase leakage, the polarization value of 1,6-diphenyl-1,3,5-hexatriene, malonaldehyde content and cell lysis were significantly elevated when cells were treated by ultrasound for 60 s; 3) cytotoxicity by ultrasound irradiation was also accompanied by an increase in production of intracellular reactive oxygen species and dissipation of mitochondria membrane potential as well as by mitochondria swelling. Presently available information indicates that the plasma membrane and mitochondria are the main targets for ultrasound treatment, and free radicals formation such as ·OH due to ultrasound cavitation may play an important role in mediating these cellular response processes. Moreover the mechanical effect might also be involved in inducing cell damage because there was significant mitochondria membrane potential loss and no visible ROS detection when cells were exposed to ultrasound for 30 s.

Element Mapping And Transmitter For Continuous Wave Ultrasound Imaging

Element mapping and transmission of continuous waves are provided ultrasound imaging. For use with multiple dimensional or large arrays, the number of receive beamformer channels or associated cables connecting the transducer array to the receive beamformer may be limited. Subarrays of signals from different elements associated with similar phasing are combined without switching. The combined subarray signals are then received beamformed to generate a continuous wave image. Receive channels without clocking or beamforming prior to a steered continuous wave Doppler beamformer maximize dynamic range and reduce the power consumption. For further or different optimization of steering continuous waves, low voltage transmitters separate from high voltage transmitters are provided for a plurality of elements.

Changes in clot lysis levels of reteplase and streptokinase following continuous wave ultrasound exposure, at ultrasound intensities following attenuation from the skull bone

BackgroundUltrasound (US) has been used to enhance thrombolytic therapy in the treatment of stroke. Considerable attenuation of US intensity is however noted if US is applied over the temporal bone. The aim of this study was therefore to explore possible changes in the effect of thrombolytic drugs during low-intensity, high-frequency continuous-wave ultrasound (CW-US) exposure.MethodsClots were made from fresh venous blood drawn from healthy volunteers. Each clot was made from 1.4 ml blood and left to coagulate for 1 hour in a plastic test-tube. The thrombolytic drugs used were, 3600 IU streptokinase (SK) or 0.25 U reteplase (r-PA), which were mixed in 160 ml 0.9% NaCl solution. Continuous-wave US exposure was applied at a frequency of 1 MHz and intensities ranging from 0.0125 to 1.2 W/cm2. For each thrombolytic drug (n = 2, SK and r-PA) and each intensity (n = 9) interventional clots (US-exposed, n = 6) were submerged in thrombolytic solution and exposed to CW-US while control clots (also submerged in thrombolytic solution, n = 6) were left unexposed to US.To evaluate the effect on clot lysis, the haemoglobin (Hb) released from each clot was measured every 20 min for 1 hour (20, 40 and 60 min). The Hb content (mg) released was estimated by spectrophotometry at 540 nm. The difference in effect on clot lysis was expressed as the difference in the amount of Hb released between pairs of US-exposed clots and control clots. Statistical analysis was performed using Wilcoxon's signed rank test.ResultsContinuous-wave ultrasound significantly decreased the effects of SK at intensities of 0.9 and 1.2 W/cm2 at all times (P < 0.05). Continuous-wave ultrasound significantly increased the effects of r-PA on clot lysis following 20 min exposure at 0.9 W/cm2 and at 1.2 W/cm2, following 40 min exposure at 0.3, 0.6, 0.9 and at 1.2 W/cm2, and following 60 min of exposure at 0.05 0.3, 0.6, 0.9 and at 1.2 W/cm2 (all P < 0.05).ConclusionIncreasing intensities of CW-US exposure resulted in increased clot lysis of r-PA-treated blood clots, but decreased clot lysis of SK-treated clots.

Encapsulation of Concentrated Protein Into Erythrocyte Porated by Continuous-Wave Ultrasound

A procedure of continuous-wave ultrasound (US)-induced hemolysis and reseal in solution containing water soluble protein was applied to a method for encapsulating concentrated protein solutions into resealed rat erythrocyte ghosts. To find a condition yielding a higher mean corpuscular concentration of encapsulated protein (MCC), we investigated the value of MCCs for various conditions. Additions of a small amount of plasma, Ca 2+ and Mg 2+ significantly increased MCC, whereas these additives did not alter the degree of hemolysis. It was suggested that plasma protect the molecular damages by the US, and that Ca 2+ and Mg 2+ physically stabilized the lipids of the erythrocyte membrane to fuse and reseal the pore induced by US. A maximal MCC of ∼50 mg/mL, which is 2.5 times the reported maximum amount encapsulated by the osmotic dialysis method, was obtained without a blood-washing procedure. (E-mail: masaaki.iino@it-chiba.ac.jp)

Continuous wave ultrasound enhances vancomycin release and antimicrobial efficacy of antibiotic‐loaded acrylic bone cement in vitro and in vivo

Although antibiotic-loaded bone cement (ALBC) is used as a drug delivery vehicle to decrease infection rates, the varied clinical effect of the antibiotic release remains controversial. The objective of this study is to investigate the enhancement of continuous wave ultrasound (CWU) on vancomycin release and antimicrobial efficacy of ALBC in vitro and in vivo. We measured vancomycin concentrations after a 0.5-h exposure of CWU. The results showed that CWU increased the drug elution by 2.57-27.44% when compared with the controls in vitro. Ultrasonic intensity and vancomycin load both had a significant effect on the cumulative drug elution at 10.5 h, with a significant interaction between each other. We also implanted ALBC specimens into hip joints of sixteen New Zealand White female rabbits after inoculations of Staphylococcus aureus around primary implants for 30 days. Vancomycin concentrations in the hip cavity and urinary elimination of vancomycin were both measured after intermittent exposures of CWU. The results showed that CWU increased local Tmax by 47.6 microg/mL and urinary elimination of vancomycin by 109.56 microg, but failed to prolong local T>MIC. On day 30 after the implantation, assessment in clinical performance, radiology, bacteriology, and histology all showed a tendency of decreased bacterial vitality and relieved inflammation in the infected hip treated by CWU. This study suggested that CWU could effectively enhance vancomycin release and antimicrobial efficacy of ALBC, which may be of clinical significance for treating prosthesis-related infections.

Effect of ultrasound on nucleated erythrocytes

In this experimental study, carp erythrocytes were used as nucleated cell models to test the hypothesis that ultrasound (US) exposure can cause the change in plasma membranes and hemoglobin. To identify target cell damage, we studied hemolysis, osmotic fragility, lipid peroxidation of red blood cells and oxidation of hemoglobin in the erythrocytes. The erythrocytes were exposed to 1 MHz continuous-wave US at the intensities of 0.61 to 2.44 W/cm 2 for 5 min. These results showed that US sonication at the intensities of 1.90 and 2.44 W/cm 2 led to an increase in the degree of hemolysis and, at the highest used intensity (2.44 W/cm 2), an increase in osmotic fragility. Ultrasound in all the used intensities induced an increase in lipid peroxidation. The results obtained showed that the level of methemoglobin has a tendency to increase after US exposure. Our results suggest that the changes in biomembranes can be due to inertial cavitation induced by US, but we cannot say which stage of the inertial event causes the damage. (E-mail: tgabryl@biol.uni.lodz.pl)

Low-intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis

Low-intensity ultrasound (US) increases tissue perfusion in ischemic muscle through a nitric oxide (NO)-dependent mechanism. We have developed a model to expose endothelial cells to well-characterized acoustic fields in vitro and investigate the physical and biological mechanisms involved. Human umbilical vein endothelial cells (HUVEC) or bovine aortic endothelial cells (BAEC) were grown in tissue culture plates suspended in a temperature-controlled water bath and exposed to US. Exposure to 27 kHz continuous wave US at 0.25 W cm(-2) for 10 min increased HUVEC media NO by 102 +/- 19% (P < 0.05) and BAEC by 117 +/- 23% (P < 0.01). Endothelial cell NO synthase activity increased by 27 +/- 24% in HUVEC and by 32 +/- 16% in BAEC (P < 0.05 for each). The cell response was rapid with a significant increase in NO synthesis by 10 s and a maximum increase after exposure for 1 min. By 30 min post-exposure NO synthesis declined to baseline, indicating that the response was transient. Unexpectedly, pulsing at a 10% duty cycle resulted in a 46% increase in NO synthesis over the response seen with continuous wave US, resulting in an increase of 147 +/- 18%. Cells responded to very low intensity US, with a significant increase at 0.075 W cm(-2) (P < 0.01) and a maximum response at 0.125 W cm(-2). US caused minor reversible changes in cell morphology but did not alter proliferative capacity, indicating absence of injury. We conclude that exposure of endothelial cells to low-intensity, low-frequency US increases NO synthase activity and NO production, which could be used to induce vasodilatation experimentally or therapeutically.

Preliminary results using ultrasound transmission for image-guided thermal therapy

The feasibility of using an acoustic camera as a real-time imaging device for thermal surgery was investigated. The study compares camera images of tissue samples taken before, during and after a volume of tissue was thermally coagulated using focused ultrasound (US). This apparatus has analogous acoustic counterparts to an optical charge couple device (CCD) camera. The setup was operated in transmission mode, with a tissue sample placed between the camera and a 10-MHz illuminating transducer. A high-intensity continuous-wave US signal from a therapeutic transducer was focused inside the sample tissue. A reversible, time-dependent variation in image intensity was observed in the region of the therapeutic sonications in all tissues tested: bovine fat and porcine and rabbit livers. Correlations between image intensities and temperatures were shown; rabbit liver resulted in a correlation coefficient (R 2) of 0.6694 and bovine fat resulted in an R 2 of 0.9455. When temperatures high enough to coagulate tissue were reached, permanent changes in the images were observed. Lesion locations and dimensions from the images were found to be comparable to the sectioned tissue samples. An R 2 of 0.919 resulted when lesion size detected from the camera was compared to the actual lesion size. Preliminary results may indicate that the camera has an application for monitoring thermal surgery. (E-mail: rlking@bwh.harvard.edu)

Combined effects of radiation and ultrasound on ICR mice in the preimplantation stage

Embryos of ICR mice at the preimplantation stage of development were used to examine the single and combined effects of ultrasound (US) and radiation. Pregnant mice were exposed to a single dose of whole body gamma radiation and/or US at 2 hpc (hours postconception) or 3 hpc. The exposure duration was 10 min with 1-MHz continuous wave US at 1 or 2 W/cm2 by ISPTA (intensities of spatial peak temporal average). Gamma irradiation of pregnant mice (2 hpc) was at 0.5 Gy at a dosage rate of 0.2 Gy/min. The rate for ultrasonic irradiation was a dose of 1 or 2 W/cm2, considered by some to be too high in therapy, such as for arthritis in the rehabilitation area of the medical application. Various malformations were recognized, and the incidence of malformations in the 0.5-Gy exposure and the control groups were compared. A greater number of malformations were observed in the 0.5-Gy exposure group relative to the 0.5-Gy plus 1.0 W/cm2 US exposure group. Therefore, the synergistic effects of radiation relate to external malformations, the number of implantations, and the rate of embryonic death due to US. It appears that US may act to repair DNA damaged by ionizing radiation. The cell cycle of the fertilized egg is delayed, which may be the mechanism by which lesions induced by ionizing radiation are healed by ultrasonic irradiation. (E-mail:gu@suzuka-u.ac.jp)

Ultrasound enhancement of fibrinolysis at frequencies of 27 to 100 kHz

Ultrasound (US) accelerates enzymatic fibrinolysis in vitro and in animal models, and may be a useful adjunctive therapy for clinical thrombolysis. Successful clinical application will depend on the selection of appropriate US parameters to optimize fibrinolytic enhancement while limiting adverse effects, including heating. Most studies have been done at megahertz frequencies, but tissue penetration is better and heating less at lower frequencies. We have, therefore, now investigated the effects of continuous-wave and pulsed US on fibrinolysis at midkilohertz frequencies. Fibrinolysis with tissue plasminogen activator (t-PA) was measured by solubilization of radiolabeled fibrin exposed to a calibrated US field in a temperature-controlled water bath. There was significant enhancement of fibrinolysis at frequencies of 27, 40 and 100 kHz, with the greatest effect observed at 27 kHz. The largest effect was observed with continuous-wave US, but significant acceleration was also observed with peak intensities of 1 W/cm 2 duty cycles of 10% and 1%. At a 10% duty cycle, there was approximately 60% of the fibrinolytic enhancement observed with continuous-wave exposure, indicating a clear advantage of pulsing to optimize fibrinolytic effect and limit exposure. We conclude that US in the range of 27 to 100 kHz is effective in accelerating fibrinolysis at intensities and pulsing conditions that minimize the probability of heating and cavitation in clinical applications. (E-mail: charles_francis@urmc.rochester.edu)

Continuous wave ultrasound evaluation of brinase treatment of chronic arterial obstruction.

Continuous wave ultrasound evaluation of brinase treatment of chronic arterial obstruction.