K. Kawabata

Enhancement of ultrasonic absorption by microbubbles for therapeutic application

It was recently reported that not only the cavitational bioeffect but also the thermal bioeffect of ultrasound can be enhanced with microbubble agents. If the ultrasonic absorption of tissues can be significantly increased in a well-controlled manner with administration of such a microbubble agent, it will be especially useful for the ultrasonic treatment of deep-seated tissues, to where ultrasonic power high enough for the treatment is difficult to deliver. The possibility of this approach was checked in a preliminary in vitro ultrasonic exposure experiment of Levovist suspension. Ultrasonic power absorbed and scattered by a microbubble was calculated through numerically solving Rayleigh-Plesset equation to analyze its nonlinear breathing motion. It is estimated that approximately 3 microbubbles in the resonant size per cubic millimeter of tissue are needed to double the tissue absorption due to ultrasonic exposure at 2 MHz. This microbubble concentration is achievable in a human body. It is also predicted that the microbubble size may need to be controlled small enough to maintain the ultrasonic penetration for efficient ultrasonic heating of tissues.

Sonodynamic approach to tumor treatment

The localization of sonochemical reactions with focused ultrasound is investigated by developing a sonochemically active tissue mimicking phantom. It is demonstrated that the sonochemical effects can be localized within a region of size not larger than typical tumors to be treated. Sonochemically efficient methods of ultrasound irradiation, which may neither require standing wave situations nor extremely high ultrasound intensity in order to induce substantial sonochemical effects, are studied. The ultrasound intensity threshold for the sonochemical reaction is drastically decreased by the second harmonic superimposition. It is also demonstrated by in vitro experiments that a gallium-deuteroporphyrin complex, ATX-70, has three times higher sonochemical activity than hematoporphyrin (Hp) and induces cell damage at twice the rate of Hp in combination with ultrasound.<<ETX>>

Schlieren observation of therapeutic field in water surrounded by cranium radiated from 500 kHz ultrasonic sector transducer

Standing-wave formation in water surrounded by a section of a human cranium, produced by a transcranial 500 kHz ultrasonic beam was observed optically. The ultrasonic beam was generated from a prototype sector-scan phased-array transducer, designed for transcranial enhancement of thrombolysis with tissue plasminogen activator (tPA). The amplitude distribution and the wavefronts of the ultrasonic field were observed in schlieren images. The stripe patterns of the standing waves were clearly seen near the sites of reflection in these images under certain acoustic conditions. No standing wave patterns were detected in basically the same arrangement with a sector-scan phased-array transducer operating at 2 MHz. These findings suggest that standing waves may be formed in the tissue at the positions of reflection by transcranial insonation of a human brain at a relatively low ultrasonic frequency, typically less than 1 MHz. This suggests further the possibility of inducing adverse cavitational effects in brain tissue.

Tissue mimicking phantom for ultrasonic elastography with finely adjustable elastic and echographic properties

We have developed a tissue-mimicking phantom for ultrasonic elastography. The phantom has tunable elastic and echographic properties. Polyacrylamide gel, a typical chemical gel in that it shows greater stability than physical gels such as gelatin or agar, provided the basis of the phantom. Fine metal-oxide particles were added to modify the echogenicity of the gel. Independent adjustment of the concentrations of acrylamide and metal-oxide particles enabled fine-tuning of the elastic and echographic properties of the phantom. The tuning was fine enough that we were able to develop a stealth phantom, which possesses a small hard region that is very difficult to detect in echography but clearly distinguishable in elastography.

Coagulation of swine liver and canine prostrate with a prototype split-focus transducer

The split-focus approach has a potential to substantially improve the throughput of coagulation HIFU treatment. A prototype split-focus transducer with two elements at 4.3 MHz combined with a small imaging probe at 6.5 MHz was constructed for transrectal treatment of a prostate. Computer simulation predicted that a coagulation volume approximately three times larger than single-spot focus would be obtained with split focus. Swine liver lobes were intraoperatively insonated for 4 s at a peak intensity of 850 W/cm/sup 2/. A lesion of coagulative necrosis three to six times larger than single-spot focus in volume was formed with the split focus. A canine prostate was then transrectally treated. A cavity, 0.35-0.45 cm/sup 3/ in volume, was formed with only four shots of split-focus insonation.

Reduction of threshold for producing sonodynamic tissue damage by second-harmonic superimposition

Induction of acoustic cavitation by progressive waves is known to require much higher ultrasonic intensity than by standing waves. It has been found that acoustic cavitation can be an order of magnitude enhanced by superimposing the second harmonic on the fundamental. Synergistic effects between the fundamental and the second harmonic in the progressive wave mode were investigated using exteriorized mouse livers suspended in degassed saline. The intensity threshold for the production of focal tissue damage paired with fractional harmonic emission was significantly lowered by second-harmonic superimposition especially when a sonochemically active porphyrin had been administered to the mouse. Insonation with second-harmonic superimposition in combination with such a sonochemically active agent may have potential use for selective tumor treatment.

In vitro hemolysis using a switched spiral focal field

An efficient method of ultrasound irradiation to induce biologically effective cavitation is presented. A sector-vortex transducer, a phased array transducer with multiple sectors and a geometric focus, is used to produce ultrasound focal fields with spirally shaped wavefronts. Clockwise and counterclockwise spiral focal fields with basically the same ultrasound power distribution but having different wavefront angles are produced by using the same array transducer. The in vitro bioeffects from the periodic switching between such a pair of spiral focal fields are investigated. Suspended rat erythrocytes were insonated for 1 min at an ultrasound frequency of 750 kHz. A significantly high hemolysis rate is observed at a switching period of 10 ms. The rate is about ten times higher than those at switching periods of 0.1 ms or 1 s. Similar switching period dependence is also seen in the enhancement of hemolysis by adding sonochemical sensitizers.<<ETX>>

P2H-6 Tissue Expansion Imaging for Tissue Coagulation Mapping During High Intensity Focused Ultrasound Therapy

Therapy monitoring based on echo-time-shift imaging during high intensity focused ultrasound (HIFU) treatment was described. The echo shift estimated by radio frequency (RF) correlation between adjacent frames is potentially useful for mapping coagulation and tissue temperature. B-mode images are also useful for real-time monitoring, but cannot show the denatured region formed below the boiling point. Echo-shift images are, however, can. They are affected by temperature-dependant changes in the speed of sound, by thermal expansion of tissues, and by tissue expansion caused by irreversibly denatured protein and the radiation force generated by HIFU. To separate the effect of radiation force from other thermal changes, we used a split-focus technique with which the peak of ultrasonic intensity can be shifted from the peak tissue temperature. Tissue expansion was mapped with a split HIFU beam with large separation in an in vitro experiment. Since the time course of tissue expansion did not follow that of the temperature change and expansion remained after cooling, it was suggested that echo-shift imaging could detect region in which coagulation occurred below the boiling temperature, which regions are could not be detected by B-mode imaging

P2D-1 High Contrast Ultrasound Imaging by Motion-Compensated Time-Averaging Method

Motion-compensated time-averaged imaging (MTI), a method of accumulating frames with a motion compensation technique using small subregions was conducted to improve power Doppler and B-mode imaging. In our previous study, MTI was shown to be able to clearly image vasculature with contrast agents without image blurring even if the target tissue was moving [Yoshikawa, H, 2006]. The purpose of this study is to investigate whether MTI is applicable to power Doppler and B-mode imaging. It was found that image qualities improved in each case. The motion artifact of a power Doppler image of rabbit kidney was reduced without blurring the image. Also, in the B-mode image of a human carotid artery, the inner membrane was clearly imaged, which is not possible with conventional imaging. The motion of carotid arteries in the slice direction leads to signal compounding at various angles in that direction and results in clear imaging without speckles. Although MTI is a powerful tool for improving ultrasound images, it incurs high computational costs because tissue motion must be compensated in every consecutive frame of an MTI image. As a feasibility test, we investigated whether we could carry out real-time MTI processing with a MAP processor (Equator Technologies, Inc.), which decreases computational cost. We estimated the cost of carrying out MTI with a MAP processor and found that it can be done at frame rates of up to 23 frames per second

MRI-compatible ultrasonic probe for minimally invasive therapy

The effects of magnetic resonance imaging (MRI)-compatible ultrasound (US) probes on MRI monitoring were evaluated. It was found that MRI-compatible US probes with backing material containing 100 ppm ferrite, did not disturb MR monitoring except within a few mm radius from the US probes position. MRI temperature monitoring of an excised swine liver irradiated with a high-intensity focused US beam from an MRI-compatible therapeutic transducer with US image guidance was then performed, and the potential usefulness of such a therapeutic system in minimally invasive therapy was demonstrated.